bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoparticles made of Fluorescence-Labelled Poly(L-lactide-co-glycolide): Preparation, Stability, and Biocompatibility
Authors: Weiss Barbara , Schaefer Ulrich F. , Zapp Josef , Lamprecht Alf , Stallmach Andreas , Lehr Claus-Michael
Published: September 2006

Nanoparticles have recently been demonstrated in a rat model to be a promising tool for targeting inflamed areas of the intestinal mucosa in inflammatory bowel diseases whilst concentrating antiinflammatory drugs at their site of action. Still, however, this novel concept has to be
proven in vivo in humans. As a first step biodegradable and biocompatible fluorescent nanoparticles were prepared and characterized to serve as markers for successful inflammation targeting in future clinical trials. To achieve stable fluorescence labelling, fluoresceinamine was covalently
bound to poly(L-lactide-co-glycolide) (PLGA) as described by Horisawa et al. The modification rate of carboxyl-end groups of the PLGA chains determined by 1H NMR was 65%. From this modified polymer, nanoparticles (FA-PLGA nanoparticles) of approximately 270 nm size were prepared
via nanoprecipitation. Apart from an initial burst effect, most of the label (>88%) appeared to be strongly bound and was leaked only slowly from the particles. In contrast, we found an immediate leakage of encapsulated sodium fluorescein with nanoparticles prepared by a double emulsion
method. In degradation experiments we studied and visualized the changes in morphology and elastic properties of the FA-PLGA nanoparticles within 15 weeks using atomic force microscopy. When FA-PLGA nanoparticles were applied on an in vitro model of the intestinal mucosa (Caco-2 cell
culture), only minor amounts of their fluorescent degradation products (∼0.02% after 6 h) were transported. In a cytotoxicity study with Caco-2 cells, FA-PLGA nanoparticles yielded an IC50 value as for plain PLGA nanoparticles. In conclusion, the polymer modification method
allows to prepare fluorescently labelled nanoparticles from a well-known biodegradable pharmaceutical polymer with sufficient stability to be monitored over a period of several days. Some initial leakage of fluorescence label appears to be unavoidable but negligible with respect to potential
absorption and cytotoxicity when applied in vivo.
Transport Characteristics of Wheat Germ Agglutinin-Modified Insulin-Liposomes and Solid Lipid Nanoparticles in a Perfused Rat Intestinal Model
Authors: Zhang Na , Ping Qineng , Huang Guihua , Han Xiuzhen , Cheng Yanna , Xu Wenfang
Published: September 2006

Wheat germ agglutinin (WGA) modified liposomes and solid lipid nanoparticles (SLNs) were evaluated for improving intestinal absorption of insulin. In an in situ local intestinal perfusion experiment, formulations containing 100 IU/kg insulin were administered to the duodenum,
jejunum, and ileum of fasted rats. As hypothesized, ileum was the best intestinal location for the absorption of insulin-containing liposomes. Serum insulin concentrations decreased for the various formulations in different absorption sites according to the following trends: Duodenum >
ileum > jejunum for WGA-modified insulin-containing liposomes; duodenum > jejunum > ileum for WGA-modified insulin-containing SLNs; ileum > jejunum > duodenum for insulin-containing liposomes; ileum > duodenum > jejunum for insulin-containing SLNs; and duodenum ≥ ileum
> jejunum for aqueous solution of insulin. These results imply that the nanoparticle type and delivery site were important factors with respect to increasing the bioavailability of insulin following oral administration. The proteolytic degradation as well as the epithelial permeability
were primary determinants influcing insulin mucosal absorption.
R4 Peptide-pDNA Nanoparticle Coated HepB Vaccine Microparticles: Sedimentation, Partitioning, and Spray Freeze Dry Bioprocesses
Authors: Knowle R. , Werner A. , DeLong R. K.
Published: September 2006

Broad therapeutic application of nucleic acid micro- and nanoparticles will require bioprocesses capable of achieving high loads of structurally intact and functionality active DNA. Here we report condensation of pDNA into nanoparticles by sedimentation through R4 peptide and partitioning
at a hydrophobic interface. ≥90% coating efficiency onto microparticles is achieved via this combined bioprocess with the pDNA retaining 85–90% intact supercoil after bioprocessing. SEM analyses of the microparticles produced therefrom reveals bound pDNA and R4 peptide nanoparticles.
HPLC and chemical analyses afford quantification of the particle-associated pDNA and R4 peptide along with lactose, raffinose, or trehalose carbohydrate stabilizer, surface coatings uniformly applied by spray freeze-drying. Administration of these particles by gene gun demonstrates delivery
to the nucleus of expressive nanoparticles and into rodents and pigs pronounced immunogenicity even after bioprocessing and accelerated degradation. These data support the discovery of a robust bioprocess platform for preparing macromolecule bound bioparticles with potential relevance beyond
simple preparation of bioactive DNA vaccine.
Nanospheres of a Bisphosphonate Attenuate Intimal Hyperplasia
Authors: Cohen-Sela Einat , Dangoor David , Epstein Hila , Gati Irith , Danenberg Haim D. , Golomb Gershon , Gao Jianchuan
Published: September 2006

The present study explored a novel strategy for attenuation of restenosis after arterial injury by a bisphosphonate encapsulated in polymeric nanoparticles (NP) for transient selective depletion of macrophages. A bisphosphonate (BP), 2-(2-Aminopyrimidino) ethyldiene-1,1-bisphosphonic
acid betaine (ISA), was successfully formulated in 400 nm sized polylactide/glycolide-based NP with high yield (69%) and entrapment efficiency (60% w/w). ISA NP, but not blank NP or free ISA, exhibited specific and significant cytotoxic effect on macrophages-like RAW 264 cells, in a dose-dependent
manner, with no inhibitory effect on the growth of smooth muscle cells (SMCs). Fluorescent pyrene-labeled NP were shown to be taken up by RAW 264 cells, but not by SMCs. Intravenously (IV) administered ISA NP (15 mg/kg, single dose on day-1) resulted in a significant attenuation of neointima
to media area ratio (N/M) by 40% and stenosis by 45% 14 days after rat carotid injury, in comparison to animals treated with free ISA, buffer or blank NP. However, the effect was not preserved 30 days post injury, and an insignificant reduction of neointimal formation was observed. Neointimal
hyperplasia was also significantly suppressed after subcutaneous (SC) injection of ISA NP (15 mg/kg, single dose on day-1), reducing both N/M and stenosis. Intraperitoneal (IP) injection of silica, a known selective toxin for macrophages, (1000 mg/kg), also resulted in a significant inhibition
of N/M and stenosis, which further reinforces the cause-effect relationship of macrophage-inactivation and the prevention of neointima formation. Biocompatible and biodegradable NP loaded with ISA characterized by high colloidal stability, reproducible activity, and high drug entrapment warrant
further consideration for restenosis therapy, and may be useful in other disease processes involving monocytes/macrophages.
Chitosan Surface-Modified Hydroxycamptothecin Loaded Nanoparticles with Enhanced Transport Across Caco-2 Cell Monolayer
Authors: Zhang Leyang , Sun Minjie , Guo Rui , Jiang Zhiping , Liu Yun , Jiang Xiqun , Yang Changzheng
Published: September 2006

This study explored the feasibility of using surface-modified nanoparticulate drug delivery system to enhance the transepithelial transport of antitumor drugs. An antitumor drug, 10-hydroxycam-ptothecin, was encapsulated into nanoparticles made of biodegradable poly(caprolactone-co-lactide)-PEG-poly(caprolactone-co-lactide)
by a novel two-step nano-precipitation method. The obtained nanoparticles had a drug loading content of 10.4% and a size of 256.3 nm, exhibiting a steady and sustained in vitro release profile. By incubation in chitosan containing medium, the drug- loaded nanoparticles could be subsequently
surface-modified with chitosan. The surface modification was monitored by dynamic light scattering method, zeta potential observation, and transmission electron microscopy, and its degree could be easily adjusted by varying the concentration of chitosan in the incubation medium. Caco-2 cell
monolayer was used as an in vitro model to evaluate the intestinal 10-hydroxycamptothecin absorption. The absorptive transport of 10-hydroxycamptothecin could be improved to some extent by drug loaded nanoparticles and could be further enhanced in the case of surface-modified nanoparticles,
suggesting that chitosan surface-modified nanoparticles may be a promising oral delivery system for antitumor drugs.
Physical Stability and Lyophilization of Poly(ε-caprolactone)-b-Poly(ethyleneglycol)-b-Poly(ε-caprolactone) Micelles
Authors: Hu Yong , Ding Yin , Li Yuan , Jiang Xiqun , Yang Changzheng , Yang Yonghua
Published: September 2006

The stability and lyophilization of core–shell PCL-PEG-PCL micelles were investigated by fluorescence spectra, DLS, DSC, WAXD, and FT-IR. The prepared micelles were not stable when they were stored in aqueous dispersion under different condition. Their size increased in the first
20 days and decreased gradually when the storage period was extended. Lyophilization experiment showed that the cryoprotective agent (glucose) was an essential additive to protect the micelles from aggregating during the lyophilization process. After lyophilizing and re-dispersion, the PCL-PEG-PCL
micelles became larger in size compared to as-prepared ones. DSC, WAXD, and IR measurements indicated the hydrogen bonding was formed between the hydroxyl group in glucose and the carbonyl group in PCL-PEG-PCL micelles. The effect of added glucose on protection of micelles from aggregation
can be explained by the formation of hydrogen bonding with PCL-PEG-PCL micelles and the formation of solid glucose matrix.
Development of Phosphorylated Glucomannan-Coated Chitosan Nanoparticles as Nanocarriers for Protein Delivery
Authors: Cuña M. , Alonso-Sande M. , Remuñán-López C. , Pivel J. P. , Alonso-Lebrero J. L. , Alonso M. J.
Published: September 2006

The aim of the present work was to develop a new nanoparticle carrier, adapted for the oral administration of proteins and their delivery to the immune system. Chitosan and phosphorylated glucomannan were chosen as major constituents of the nanoparticles. Chitosan nanoparticles were
formed by ionic gelation and then coated with glucomannan. Two different protocols were adopted for the formation of the glucomannan coating: protocol I, in which chitosan nanoparticles were isolated before their coating; protocol II, in which chitosan nanoparticles were not isolated, but
coated with glucomannan in the presence of free chitosan. The results showed that, under the selected formulation conditions, the sizes of the nanoparticles ranged between 170 and 300 nm and their zeta potential values were inverted from positive to negative by the glucomannan coating. The
nanoparticles prepared by the two protocols could be freeze-dried, in the presence or absence of cryoprotective agents, preserving their original characteristics. The results of the stability study evidenced the positive role of the glucomannan coating in preventing the aggregation of the
nanoparticles in buffered media. Finally, the association of the inmunomodulatory protein complex P1 to the chitosan-glucomannan nanoparticles was investigated. The results showed that the association was not dependent on the chitosan: sodium tripoliphosphate ratio, but it was significantly
affected by the presence of sodium phosphate in the protein structure.
siRNA Drug Delivery by Biodegradable Polymeric Nanoparticles
Authors: Yuan Xudong , Li Ling , Rathinavelu Appu , Hao Jinsong , Narasimhan Madhusudhanan , He Matthew , Heitlage Viviene , Tam Linda , Viqar Sana , Salehi Mojgan
Published: September 2006

RNA interference (RNAi) is an emerging technology in which the introduction of double-stranded RNA (dsRNA) into a diverse range of organisms and cell types causes degradation of the complementary mRNA. It offers a broad spectrum of applications in both biological and medical research.
Small interference RNA (siRNA) was recently explored for its therapeutical potential. However, the drug delivery of siRNA oligos is very novel and is in great need of future research. To this end, a biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticle drug carrier system
was prepared to load siRNA oligos with desired physicochemical properties. The nanoparticles were characterized by scanning electron microscopy and laser diffraction particle sizer. The delivery of siRNA into the targeted 293T cells was observed using fluorescent-labeled double-stranded Cy3-oligos.
The model siRNA oligos, si-GFP-RNA, were also successfully loaded into PLGA nanoparticles and delivered in 293T cells. The gene silencing effect and the inhibition of GFP expression were investigated using fluorescent microscopy. Both positive and negative controls were used to compare with
the new siRNA nanoparticle delivery system. It was found that nanoparticles offered both effective delivery of siRNA and prominent GFP gene silencing effect. Compared to conventional carrier systems, the new biodegradable polymeric nanoparticle system may also offer improved formulation stability,
which is practically beneficial and may be used in the future clinical studies of siRNA therapeutics.
Design and Characterisation of Poly(lactide-co-glycolide) Small Particulate Systems for the Delivery of Immunostimulant CpG Oligonucleotide
Authors: Shakweh Monjed , Fattal Elias
Published: September 2006

The aim of this study was to develop and characterize biodegradable small particles of poly(lactide-co-glycolide) (PLGA) as oral vehicle for immunostimulatory oligonucleotide (ODN-CpG). Three different polymers were used as surface stabilizing agents (SSA): polyvinyl alcohol (PVA),
hydrophobically modified hydroxyethylcellulose (HMHEC), or polyethylenimine (PEI). Particle surface was characterized as well as ODN-CpG release kinetics. All particles were found to be around 1 μ. Particles of PLGA-PVA and PLGA-HMHEC were spherical in shape with a smooth surface
whereas PLGA-PEI particles were porous. The presence of ODN-CpG within the particle matrix was confirmed in all particle type using scanning laser confocal microscopy. Particle surface assayed by XPS, zeta potential analysis, and evaluation of particle surface hydrophobicity suggested that
a significant amount of SSA remains associated onto particle surface. Release profiles evidenced that ODN-CpG release was strongly dependent on particle surface properties. 100% of encapsulated ODN-CpG was released from PLGA-PVA and PLGA-HMHEC particles 37 days after incubation in a buffer
solution, whereas only 25% were released from PLGA-PEI particles. ODN-CpG can therefore be nicely entrapped in several types of small particles displaying a prolonged and controlled release upon time. In addition, particle surface is not modified by the presence of ODN-CpG.
Improved Oral Delivery of Paclitaxel Following Administration in Nanoemulsion Formulations
Authors: Tiwari Sandip B. , Amiji Mansoor M.
Published: September 2006

Nanoemulsion formulations were designed for enhancing the oral bioavailability of hydrophobic drugs. Paclitaxel was selected as a model hydrophobic drug, which is also a substrate for the P-glycoprotein efflux system. The oil-in-water (o/w) nanoemulsions were formulated with pine nut
oil as the internal oil phase, egg lecithin as the primary emulsifier, and water as the external phase. Stearylamine and deoxycholic acid were used to impart positive and negative charge to the emulsions, respectively. Nanoemulsions were prepared by sonication method and characterized for
particle size and surface charge. The control and nanoemulsion formulations with tritiated [3H]-paclitaxel were administered orally to female C57BL/6 mice and the distribution of the drug was examined. The formulated nanoemulsions had a particle size range of ∼90–120 nm
(laser diffraction method)and zeta potential values ranging from −56 mV to +34 mV. Following oral administration, a significantly higher concentration of paclitaxel was observed in the systemic circulation when administered in the nanoemulsion relative to control aqueous solution. The
absorbed drug was found to be distributed in the liver, kidneys, and lungs. The results of this study suggest that nanoemulsions are promising novel formulations that can enhance the oral bioavailability of hydrophobic drugs, like paclitaxel.
The Blood-Brain Barrier and Brain Drug Delivery
Authors: Koziara J. M. , Lockman P. R. , Allen D. D. , Mumper R. J.
Published: September 2006

The present report encompasses a thorough review of drug delivery to the brain with a particular focus on using drug carriers such as liposomes and nanoparticles. Challenges in brain drug delivery arise from the presence of one of the strictest barriers in vivo—the blood-brain
barrier (BBB). This barrier exists at the level of endothelial cells of brain vasculature and its role is to maintain brain homeostasis. To better understand the principles of brain drug delivery, relevant knowledge of the blood-brain barrier anatomy and physiology is briefly reviewed. Several
approaches to overcome the BBB have been reviewed including the use of carrier systems. In addition, strategies to enhance brain drug delivery by specific brain targeting are discussed.
Arsonoliposomes: Novel Nanosized Arsenic-Containing Vesicles for Drug Delivery
Authors: Fatouros Dimitris G. , Ioannou Panayiotis V. , Antimisiaris Sophia G.
Published: September 2006

Natural and synthetic arsenolipids, have been discovered, synthesized, and evaluated for their biological activity. Arsonolipids, are analogs of phosphonolipids, in which P has been replaced by As. The synthesis of arsonolipids has been explored and a simple one-pot method with high
yield is currently available for their preparation. However, although arsonolipids posses interesting biophysical and biochemical properties their anticancer or antiparasitic activity is not considered adequate for therapeutic applications. But when arsonolipids are incorporated in liposomes,
the vesicles formulated have interesting possibilities, as seen in a number of studies. In cell culture studies, nanosized arsonolipid-containing liposomes or else arsonoliposomes, showed increased toxicity against cancer cells (compared to that of arsenic trioxide) but at the same time were
less toxic than arsenic trioxide for normal cells. Furthermore, arsonoliposomes also demonstrate antiparasitic activity in vitro. Nevertheless, As is rapidly cleared from blood after in vivo administration of arsonoliposomes, and this will highly limit possible therapeutic applications.
In addition, the fact that arsonoliposomes were observed to aggregate and subsequently fuse into larger particles in presence of cations, may also be considered as a problem. Thereby, methods to modulate the stability of arsonoliposomes and, perhaps, their in vivo distribution (as surface
property modification) are currently being investigated. In very recent experiments it has been shown that arsonoliposome pegylation results in the formation of liposomes with very high membrane integrity. In addition, pegylation results in increased physical stability of arsonoliposomes and
abolishment of cation-induced aggregation and fusion. Nevertheless, further in vivo studies are required in order to prove if pegylation alters arsonoliposome in vivo kinetics in a positive way, without affecting their activity. From studies performed thus far it is concluded
that arsonoliposomes are nanosized-vesicles with interesting properties that justify further exploitation towards the development of therapeutic systems for cancer or parasitic diseases.
Surface-Modified and Conventional Nanocapsules as Novel Formulations for Parenteral Delivery of Halofantrine
Authors: Mosqueira Vanessa Carla Furtado , Legrand Philippe , Barratt Gillian
Published: September 2006

The aim of this work was to develop a stable injectable formulation of the antimalarial drug halofantrine (Hf) based on nanocapsules (NC) prepared from biodegradable polymers with Miglyol® 810N as the oily core. Poly(D,L-lactide) PLA and its copolymers with poly(ethyleneglycol)
(PLA-PEG) were used together with the surfactants poloxamer 188 and lecithin to yield NC with different surface properties. Highly efficient loading of the free base form of Hf was obtained; zeta potential measurements indicated that a part of the associated Hf was at the NC surface, interacting
with the lecithin. NC were 150–250 nm in diameter and more stable on storage than nanoemulsions formed from oil and lecithin without polymer. The most stable NC, showing minimal size changes and flocculation, were those with a high density of 20-kDa PEG chains covalently grafted at the
surface. Hf release from NC occurred mainly by partition with the external medium. In PBS, even when Tween 80 was added, release was limited to 20% of the total content, whatever the formulation. Addition of serum to the medium allowed complete and rapid release from PLA NC stabilized with
adsorbed poloxamer 188, because of the high affinity of Hf for lipoproteins. However, the presence of covalently grafted PEG chains at the surface limited release by providing a hydrophilic steric barrier at the particle surface. A dense coverage with long PEG chains provided the best reduction
of release. Such systems could constitute a long-circulating intravenous formulation of Hf for treating severe malaria.
Bioadhesive Mannosylated Nanoparticles for Oral Drug Delivery
Authors: Salman Hesham H. , Gamazo Carlos , Campanero Miguel A. , Irache Juan M.
Published: September 2006

The aim of this work was to design mannosylated Gantrez® AN nanoparticles (M-NP) and to describe their gut bioadhesive properties in order to develop a promising carrier for future applications in oral drug delivery. For that purpose, the process of the nanoparticles
coating with mannosamine was optimized by the incubation of Gantrez® AN nanoparticles with different volumes of mannosamine aqueous solutions at different times. Then, the nanoparticles were characterized by measuring the size, zeta potential, mannosamine content, and concanavalin
A (Con A) binding. Furthermore, in vivo quantitative bioadhesion study and kinetic analysis of the bioadhesion curves were performed after oral administration to rats of fluorescently labelled nanoparticles. The selected mannosylated nanoparticles (M-NP1 and M-NP10) were of homogenous
sizes (about 300 and 200 nm), negatively charged and successfully coated with 36 and 18 μg mannosamine/mg NP, respectively. In vitro agglutination assay using Con A confirmed the successful coating of nanoparticles with mannosamine. The gut distribution profile of M-NP1 indicated
a stronger bioadhesive capacity than M-NP10 and non-mannosylated ones, 1 h post-administration. Interestingly, M-NP1 showed an important ileum tropism where around 20% of the given dose remained adhered. Besides, the kinetic parameters of the bioadhesion profile of M-NP1 indicated their higher
bioadhesive capacity with Qmax and AUCadh about 2-times higher than control ones. Moreover, fluorescence microscopy corroborated the stronger interactions of M-NP1 with the normal mucosa and demonstrated a strong uptake of these carriers by Peyer's patches. In
conclusion, we propose that mannosylated nanoparticles could be a promising non-live vector for oral delivery strategies.
Management of Cardiovascular Diseases with Micro Systems and Nanotechnology
Authors: Kong L. X. , Peng Z. , Sugumar D.
Published: September 2006

Cardiovascular diseases are the leading cause of death and morbidity in industrialized nations and are becoming an urgent health problem for all nations due to the unstoppable trend of an ageing and obese population. Due to the rapid development of micro total analysis systems (μTAS)
and nanotechnology in recent years, they will play an important role in the diagnosis, management, and therapy of cardiovascular diseases. It is envisaged that the micro and nanotechnologies developed for treating other diseases shall be explored for cardiovascular applications to reduce the
research effort required for commercializing the devices and drugs to meet the increasing demand of the cardiovascular patients.
Liposome Size Analysis by Dynamic/Static Light Scattering upon Size Exclusion-/Field Flow-Fractionation
Authors: Hupfeld Stefan , Holsæter Ann Mari , Skar Merete , Frantzen Christer B. , Brandl Martin
Published: September 2006

The aim of the current study was to analyse the particle size distribution of a liposome dispersion, which contained small egg phosphatidylcholine vesicles and had been prepared by high-pressure homogenisation, by various size analysis techniques. Such liposomes were chosen since they
can be looked at as a prototype of drug nano-carriers. Three sub-micron particle size analysis techniques were employed: (1) fixed-angle quasi-elastic laser light scattering or photon correlation spectroscopy (PCS), (2) size exclusion chromatographic (SEC) fractionation with subsequent (off-line)
PCS size-analysis and quantification of the amount of particles present in the sub-fractions, and (3) field-flow-fractionation coupled on-line with a static light scattering and a refractive index (RI)-detector. When designing liposome-based drug carrier systems, a reliable and reproducible
analysis of their size and size distribution is of paramount importance: Not only does liposome size influence the nanocarrier's in-vitro characteristics such as drug loading capacity, aggregation and sedimentation but also it is generally acknowledged that the pharmacokinetic behaviour
and biodistribution of the carrier is strongly size-dependent. All three approaches of liposome size analysis used here were found to yield useful results, although they were not fully congruent. PCS indicated either a broad, mono-modal, log-normal size distribution in the range of below 20
to over 200 nm in diameter, or alternatively, a bimodal distribution with two discrete peaks at 30 to 70 nm and 100 to over 200 nm. Which of the two distribution models represented the best fit depended primarily on the data collection times used. In contrast, both fractionating techniques
revealed a size distribution with a large, narrow peak well below 50 nm and a minor, broad, overlapping peak or tail extending to over 100 nm in diameter. The observed differences in liposome size distribution may be explained by the inherent limitations of the different size analysis techniques,
such as the detection limit and the fact that PCS is overemphasizing bigger particle sizes.
Effect of Hydroxyapatite Nanoparticles on Ibuprofen Release from Carboxymethyl-Hexanoyl Chitosan/O-Hexanoyl Chitosan Hydrogel
Authors: Liu Tse-Ying , Liu Ting-Yu , Chen San-Yuan , Chen Shian-Chuan , Liu Dean-Mo
Published: September 2006

In order to explore the effect of nanofiller on the regulation of the drug release behavior from microsphere-embedded hydrogel prepared by carboxymethyl-hexanoyl chitosan (HNOCC) and O-hexanoyl chitosan (OHC), the release kinetics was investigated in terms of various amounts
of calcium-deficient hydroxyapatite (CDHA) nanoparticles incorporated. HNOCC is a novel chitosan-based hydrophilic matrix with a burst release profile in a highly swollen state. The drug release kinetics of the HNOCC hydrogel can be regulated by incorporation of well-dispersed CDHA nanoparticles.
It was found that the release duration of ibuprofen (IBU) from HNOCC was prolonged with increasing amounts of CDHA which acts as a crosslink agent and diffusion barrier. On the contrary, the release duration of the IBU from OHC (hydrophobic phase) was shortened through increasing the CDHA
amount over 5%, which is due to the hydrophilic nature of the CDHA nanoparticles destroying the intermolecular hydrophobic interaction and accelerating OHC degradation. Thus, water accessibility and molecular relaxation were enhanced, resulting in a higher release rate. In addition, sustained
and sequential release behavior was achieved by embedding the OHC microspheres (hydrophobic phase) into the HNOCC (hydrophilic phase) matrix, which could significantly prolong the release duration of the HNOCC drug-loaded implant.
Development and Comparative Anti-Microbial Evaluation of Lipid Nanoparticles and Nanoemulsion of Polymyxin B
Authors: Pattani A. S. , Mandawgade S. D. , Patravale Vandana B.
Published: September 2006

Polymyxin B is a decapeptide, mainly used for the treatment of gram-negative bacteremia. It was anticipated that a prolongation of release may lead to a more efficacious therapy. Lipid nanoparticles and nanoemulsion were formulated and comparatively evaluated for their properties. Lipid
nanopraticles of Polymyxin B Sulphate with a mean particle size of 186.9 nm (Polydispersity Index 0.235) were prepared by nano-precipitation technique and nanoemulsion was prepared under the conditions of spontaneous formation with a mean globule size 125.0 nm (Polydispersity Index 0.291).
The lipid nanoparticles were screened for lipid load from 0.1–1% along with 1–10% surfactant while in the optimization of nanoemulsion different ratios of oil, surfactant, and co-surfactant were evaluated. The developed systems were taken up for comparative anti-microbial study
against a sensitive strain of E. coli using Turbidimetry as the method for monitoring the growth of microorganisms in a time dependent manner. Results of the study using ANOVA revealed an initial comparable activity with no statistical difference between the free drug, lipid nanoparticles,
and the nanoemulsion. The anti-microbial effect was significantly sustained by lipid nanoparticles over a period of 18 hr but could not be sustained in case of nanoemulsion after 12 hr. Further, in order to assess anti-microbial activity of the developed delivery templates, a similar study
was carried out using the lipid nanoparticles and nanoemulsion without the incorporation of drug. The results showed only a mild anti-microbial action for drug-free lipid nanoparticles but significant activity was exerted by drug-free nanoemulsion against plain drug throughout the study. It
was concluded that the developed lipid nanoparticles and nanoemulsion are promising delivery vectors for the anti-microbial drugs. Further, lipid nanoparticles could give an initial as well as sustained effect while the nanoemulsion was capable of exerting potent effect for a shorter period
of time.
Camptothecin in Sterically Stabilized Phospholipid Nano-Micelles: A Novel Solvent pH Change Solubilization Method
Authors: Koo Otilia M. Y. , Rubinstein Israel , Onyuksel Hayat
Published: September 2006

Camptothecin (CPT) is a topoisomerase I inhibitor that acts against a broad spectrum of cancers. Unfortunately clinical application of CPT is limited by insolubility, instability, and toxicity problems. To circumvent these delivery problems of CPT, we propose biocompatible, targeted
sterically stabilized micelles (SSM) as nanocarriers for CPT (CPT-SSM). SSM composed of polyethylene glycol (PEGylated) phospholipids are attractive nanocarriers for CPT delivery because they are sufficiently small to extravasate through the leaky microvasculature of tumor and inflamed tissues
for passive targeting. The purpose of this study was to develop a novel method of preparing CPT-SSM based on its pH dependent, reversible carboxylate-lactone conversion chemistry. CPT carboxylate was added to SSM at pH 5 that favored the formation of active but hydrophobic CPT lactone for
spontaneous association with SSM. The kinetics of CPT conversion and CPT-SSM formation, and the effect of varying CPT-PEGylated phospholipid molar ratio on CPT-SSM properties and CPT solubilization were evaluated. CPT converted gradually from the carboxylate form to lactone, and CPT-SSM were
formed after 12 h incubation. The mean size of CPT-SSM was ∼14 nm. CPT solubilization (∼12 μg/ml) and other CPT-SSM micelle properties did not change significantly with increasing CPT to PEGylated phospholipid molar ratios using this novel method, unlike the coprecipitation/reconstitution
technique previously reported. This reproducible CPT solubilization in SSM was attributed to avoidance of drug aggregate formation by this method. The advantages of our solvent pH change method to prepare CPT-SSM support further investigations of this approach to other hydrophobic drugs similar
to CPT in chemistry and also CPT molecular solubilization in other nanocarriers.
Polymeric Nanofibers as Novel Carriers for the Delivery of Therapeutic Molecules
Authors: Kumbar Sangamesh G. , Nair Lakshmi S. , Bhattacharyya Subhabrata , Laurencin Cato T.
Published: September 2006

Nanotechnology and nanoscience are relatively new technological endeavors that encompass the study, control, manipulation, and assembly of multifarious nanoscale components into materials, systems and devices to serve human interest and needs. Among the various currently used nanostructures
for high technology applications polymeric nanofibers have received immense interest due to the ease of fabrication, controllable size/shape, and properties. Polymeric nanofibers have been extensively investigated for diversified applications, including filtration, barrier fabrics, wipes,
personal care, biomedical, and pharmaceutical applications. This review mainly focuses on the fabrication of therapeutic agent loaded polymeric nanofibers and their controlled/sustained release behavior for the delivery of these active agents for various therapeutic applications. The nonwoven
biodegradable polymeric nanofiber matrices are currently being reported as topical/local therapeutic agent delivery systems and as resorbable/biodegradable gauze for wound healing applications.
Preparation and Characterization of Thermosensitive Submicron Particles for Gene Delivery
Authors: Özdemir Nalan , Tuncel Ali , Kang Myungchan , Denkbş Emir Baki
Published: September 2006

In this study, a new thermosensitive material was proposed as a carrier for gene delivery. The thermosensitive submicron particles were synthesized by the dispersion copolymerization of N-isopropylacylamide (NIPA) with a relatively new, cationic comonomer, N-3-dimethylamino-propylmethacrylamide
(DMAPM) with higher ionization ability with respect to the commonly used cationic comonomers. To achieve particle sizes smaller than 1 μm, suitable for gene delivery, the total monomer concentration in the dispersion copolymerization was kept at a sufficiently low level. The size
of poly(NIPA-co-DMAPM) particles was determined as 454 nm, by AFM in dry state. The poly(NIPA-co-DMAPM) particles showed both temperature and pH sensitivity in the aqueous media. The plasmid DNA adsorption onto the thermosensitive cationic particles was investigated at different temperatures
and pHs. The adsorbed amount of plasmid DNA onto the particles was significantly increased by the introduction of cationic comonomer. The equilibrium plasmid DNA adsorptions up to 13 mg/g dry particles were achieved at physiological pH. Approximately 36% w/w of adsorbed plasmid could be desorbed
from the cationic nanolatex. The results of biocompatibility studies performed with mouse fibroblast cells showed the suitability of thermosensitive cationic particles for intended application.
Electrospun Multifunctional Diclofenac Sodium Releasing Nanoscaffold
Authors: Nikkola L. , Seppälä J. , Harlin A. , Ndreu A. , Ashammakhi N.
Published: September 2006

Electrospinning is a method utilized to produce nano-scale fibers for tissue engineering applications. A variety of cells are attracted by nano scale surfaces and structures probably due to the similarity of their natural environment scale. In this study, diclofenac sodium (DS) releasing
nanofibers were manufactured via electrospinning process. Poly(95 ε-capro/5 D,L-lactide) was dissolved into acetic acid to form a 20% w/v solution. 2% w/w of DS was then added into the polymer solution and stirred homogenously. About 1 g of polymer/drug solution was spun onto the
collector under electrostatic conditions. The distance between needle tip and sample collector was arranged to 10 cm and applied electric field was 2 kV/cm. Release rate of DS was measured by using UV/VIS spectrophotometer. Resulted highly porous nanofiber scaffold was about 2 mm thick and
the diameter of nanofibers was approximately 130 nm. Structure included in also spheres with approximately diameter of 3.30 μm. About 45% of DS was released during the first 24 hours and after that the release decreased to almost zero value. After 35 days release rate increased.
This study revealed that manufacturing of highly porous DS releasing nanoscaffold by electrospinning process is feasible. Having fast DS release rate nanofibrous scaffold made of poly(95 ε-capro/5 D,L-lactide)can be of benefit for applications where immediate control of tissue
reaction is needed.
Stability Studies on Colloidal Suspensions of Polyurethane Nanocapsules
Authors: Bouchemal K. , Briançon S. , Couenne F. , Fessi H. , Tayakout M.
Published: September 2006

Generally nanocapsules suspensions are a colloidal system in a metastable state, there is aggregation due to attraction and repulsion forces between particles. The objective of this work was to bring the role of the polymeric membrane in the protection of the active drug against damaging
caused by external agents and to select the monomer which leads to obtain stable formulation with the highest possible payload of the active drug. The stability testing involving visual aspect, particle size measurement, transmission electron microscopy (TEM) examination, and drug loss was
conduced after 6 months of storage at different temperatures (4, 25, and 45 °C). The colloidal suspensions of nanocapsules were obtained using the combined interfacial polycondensation and spontaneous emulsification, the technique was used to encapsulate α-tocopherol using
polyurethanes polymers. It is a one step procedure: An organic phase composed of a water miscible solvent (acetone), lipophilic monomer (Isophorone diisocyanate IPDI), oil, and a lipophilic surfactant, is injected in an aqueous phase containing hydrophilic monomer (diol with various molecular
weight: 1,2-ethanediol (ED), 1,4-butanediol (BD), and 1,6-hexanediol (HD)) and hydrophilic emulsifying agent. The water miscible solvent diffuses to the aqueous phase, the oil precipitates as nano-droplets, and the two monomers react at the interface, forming a membrane around the nanoemulsion
leading to nanocapsules. A good physical stability of suspensions corresponds to absence of symptoms such as sedimentation or agglomeration, significant size change and α-tocopherol degradation due to external agents such as oxygen, temperature, and ultraviolet (UV) irradiation.
The size of nanocapsules before storage was about 232±3, 258±29, and 312±4 nm for ED, BD, and HD, respectively. After 6 months of storage, polyurethanes nanocapsules possess good stability against aggregation at 4 and 25 °C. Comparing results obtained using different
monomers, it reveals that the polyurethane based on HD offers good protection of α-tocopherol against damaging caused by the temperature and UV irradiation.
Development of a Novel Vaccine Delivery System Based on Gantrez Nanoparticles
Authors: Gómez Sara , Gamazo Carlos , Roman Beatriz San , Vauthier Christine , Ferrer Marta , Irache Juan M.
Published: September 2006

The adjuvant capacity of a novel vaccine vector "Gantrez-nanoparticles" (NP) towards coated or encapsulated ovalbumin (OVA) was investigated. OVA nanoparticles were prepared by a solvent displacement method previously described. The protein was incorporated during the manufacturing
process (OVA-encapsulated nanoparticles) or after the preparation (OVA-coated nanoparticles). The mean size of the different nanoparticle formulations was lower than 300 nm, and the OVA content ranged approximately from 67 μg/mg nanoparticles (for OVA-coated nanoparticles) to 30
μg/mg nanoparticles (for OVA-encapsulated nanoparticles). All the OVA-NP formulations were capable of amplifying the antibodies titres (IgG1 and IgG2a) in mice after a single subcutaneous inoculation with respect free OVA or OVA adsorbed to Alum. Furthermore, the elicited response
was, for some formulations, predominantly Th1 subtype. Thus, the formulation that contained mainly the antigen inside, and with a low concentration of cross-linking agent, displayed the best potential to induce a Th1 response after 35 days post-immunisation. These results are highly suggestive
for the use of Gantrez nanoparticles as an efficient antigen delivery system, especially when a long lasting Th1 cytokine response is required.
Drug Solubilization and Delivery from Cyclodextrin-Pluronic Aggregates
Authors: Rodriguez-Perez A. I. , Rodriguez-Tenreiro C. , Alvarez-Lorenzo C. , Concheiro A. , Torres-Labandeira J. J.
Published: September 2006

Colloidal systems based on Pluronic® F127 (PF127) and hydroxypropyl-beta-cyclodextrin (HPβCD) have been characterized with a view to their potential use as delivery systems of hydrophobic drugs. Complexation of PF127 and HPβCD was evaluated by
surface tension measurements, 1H-NMR spectroscopy and transmission electron microscopy. The critical micellar concentration, CMC, at 25 °C of PF127 (0.39 mM in pH 5.8 and 7.4 phosphate buffers, and 0.59 mM in pH 4.5 acetic/acetate and lactic/lactate buffers) was shifted to higher
values by the addition of 38.17 mM HP CD (CMCapp = 1.18 mM). This is related to the threading of HPβCD onto the PF127 chains, as confirmed by 1H NMR experiments. HPβCD at this concentration notably raised the sol–gel transition temperature;
the minimum PF127 concentration required for providing gelling systems in physiological environments being 13.4 mM. Both HPβCD and PF127 by themselves are able to notably increase the solubility of sertaconazole (SN). At HPβCD concentrations below 80 mM, an additive
effect of both components on SN solubility was observed. At greater HPβCD concentrations, a non-additive increase occurred, which is related to the complexation of some PF127 unimers with HPβCD molecules, decreasing the total number of micelles and HPβCD
cavities available for interacting with SN. The 13.4 mM PF127/38.17 mM HPβCD system, able to increase up to 100 times the SN solubility in pH5.8 phosphate buffer, showed temperature-dependent drug diffusion coefficients, able to control the release for one week at 37 °C.
Molecular Electrostatic Potentials in the Design of Dendrimers for the Delivery of Glitazones
Authors: Bharatam Prasad V. , Sundriyal Sandeep
Published: September 2006

Glitazones are PPARγ agonistic insulin sensitizers used clinically for the treatment of type-2 diabetes. The delivery of these compounds with the help of dendrimers is possible. Ab initio MO calculations and MESP analysis indicate that the dendrimers with complementary
electrostatic potential to glitazones can be designed. The estimated binding strength between one arm of dendrimer and thiazolidinedione is about 15–20 kcal/mol. This binding strength originates from three hydrogen bonds between the dendrimer and each molecule of glitazone. This binding
strength is quite suitable for drug encapsulation on the dendrimer based nanoparticles and can be employed for drug delivery.
Design and Evaluation of a Self-Adhesive Naproxen-Loaded Film Prepared from a Nanoparticle Dispersion
Authors: Ganem-Quintanar Adriana , Silva-Álvarez Marlene , Álvarez-Román Rocío , Casas-Alancaster Norma , Cázares-Delgadillo Jennyfer , Quintanar-Guerrero David
Published: September 2006

Naproxen-loaded nanoparticles were used to prepare, in a one-step process, unilaminar films of Eudragit E-100 (EE-100), avoiding the use of organic solvents and assuring the homogeneity and molecular dispersion of the drug. Nanoparticle films (NP-F) and conventional films (CV-F, prepared
by casting of methanolic solutions onto a Teflon disc) were assayed by their mechanical properties, skin adhesivity, and calorimetric studies to compare their behavior. Different proportions of plasticizer (triacetin) were included to evaluate the quality of the films. Film characterization
included in vitro drug release studies through a cellulose membrane using Franz-type cells, and in vivo stratum corneum penetration experiments by the tape stripping technique. The results showed that NP-F were semi-transparent to transparent, suggesting a good compatibility
between naproxen and EE-100. Differential calorimetric studies (DSC) confirmed a molecular dispersion of naproxen in the EE-100 matrix. Taking into account the mechanical properties of the films, a 20% triacetin concentration can be considered as optimal for both types of films. The in
vitro release data obtained from both systems (NP-F and CV-F) followed the Higuchi's model for matrix systems, with the Fickian diffusion (t0.5) being the main release mechanism. Concerning the in vivo penetration studies, no statistical differences were found
for the penetrated amount of naproxen across the stratum corneum and the depth of penetration for the two films and between the three contact times (2, 4, and 6 h). The films formulated from nanoparticle dispersions (NP-F) were shown to be effective for the transdermal administration of naproxen,
and can be considered as an interesting alternative for the preparation of films with several technological advantages.
Human Vascular Endothelial Cells in Primary Cell Culture for the Evaluation of Nanoparticle Bioadhesion
Authors: Löhbach Christoph , Neumann Dirk , Lehr Claus-Michael , Lamprecht Alf
Published: September 2006

Nanoparticles (NP) are employed in various therapeutic approaches for innovative drug delivery strategies. Among them, there is drug delivery to the brain and sustained release forms for intravenous drug delivery. In order to optimize drug carriers and to elucidate involved mechanisms
such as bioadhesion and cellular uptake, NP were surface modified and analyzed for their interaction with human endothelial cells in cell culture. Fluorescently labeled NP of different diameters (50 to 1000 nm) were surface modified either by simple adsorption of chitosan or by covalent binding
to the lectin ulex europaeus agglutinin and thereafter applied to human endothelial cells for different incubation periods. After incubation with NP the binding of NP was quantified directly by the fluorescence emission signals from the cell layers. In order to visualize the binding behaviour,
NP were localized three-dimensionally in the cell layer by confocal laser scanning microscopy. Cell binding experiments in phosphate buffer were observed to be particle size dependent with the 50 nm NP showing the highest binding percentage over all experiments. Binding decreased with increasing
particle diameter and shorter incubation interval. The adhesion was further enhanced by NP surface modifications in the order blank < chitosan < lectin. The presence of plasma proteins enhanced the adhesiveness of chitosan coated NP, while the binding of lectin coated NP was inhibited.
Experiments at 4 °C indicated the involvement of an active process in the binding of NP to endothelial cells.