Daunorubicin oral bioavailability enhancement by surface coated natural biodegradable macromolecule chitosan based polymeric nanoparticles
Authors: Mohd Amir
Mohammed Jafar
Niyaz Ahmad
Md Sarafroz
Khalid Umar
Faheem Hyder Pottoo
Md Aftab Alam
Rizwan Ahmad
Farhan Jalees Ahmad
Journal: International Journal of Biological Macromolecules (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Biodegradable polymers; DAUN–NPs; Daunorubicin; In vitro cell line studies; Pharmacokinetic analysis
Affiliations: Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia; Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia. Electronic address: ., Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia., Department of Pharmaceutics, School of Medical and Allied Sciences, Galgotias University, Gautam Budh Nagar, Greater Noida 201310, India., Nanomedicine Lab, Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, Hamdard Nagar, New Delhi, India., Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia., Department of Pharmaceutical Chemistry, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia., Department of Pharmaceutics, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia., School of Chemical Sciences, Universiti Sains Malaysia, 11800 Pulau Pinang, Malaysia.

Abstract:  Background: Daunorubicin hydrochloride (DAUN·HCl), due to low oral bioavailability poses the hindrance to be marketed as an oral formulation. Aim of the study: To develop a natural biodegradable macromolecule i.e. Chitosan (CS)-coated-DAUN-PLGA-poly(lactic-co-glycolic acid)-Nanoparticles (NPs) with an aim to improve oral-DAUN bioavailability and to develop as well as validate UHPLC-MS/MS (ESI/Q-TOF) method for plasma quantification and pharmacokinetic analysis (PK) of DAUN. Results: A particle size (198.3 ± 9.21 nm), drug content (47.06 ± 1.16 mg/mg) and zeta potential (11.3 ± 0.98 mV), consisting of smooth and spherical shape was observed for developed formulation. Cytotoxicity studies for CS-DAUN-PLGA-NPs revealed; a comparative superiority over free DAUN-S (i.v.) in human breast adenocarcinoma cell lines (MCF-7) and a higher permeability i.e. 3.89 folds across rat ileum, as compared to DAUN-PLGA-NPs (p &lt; 0.01) inhuman colon adenocarcinoma cell line (Caco-2). For PK, CS-DAUN-PLGA-NPs as compared to DAUN-S, exhibited a 10.0 fold higher bioavailability in Wister rat's plasma due to presence of a natural biodegradable macromolecule i.e. CS coated on the PLGA-NPs. With regard to bioanalytical method, easy as well as a rapid method for DAUN-plasma quantification was developed as; 2.75 min and 528.49/321.54 m/z for DAUN along with 1.94 min and 544.36/397.41 m/z for IS i.e. Doxorubicin, for elution time and transition, respectively. Conclusion: A novel natural biodegradable approach used in the preparation of CS coated DAUN-NPs for oral administration of DAUN is reported in this study which is can be utilized as an alternate for intravenous therapy. 

Retracted: No

PubPeer comments:
 Fig. 3.  Characterization of Daunorubicin (DAUN), PLGA, Chitosan and CSu2013DAUNu2013PLGAu2013NPs . ![file] The Daunorubicin FT-IR spectrum does not seem to have been plotted on the same equipment as the others. The composite spectrum differs from that of plain chitosan in three short segments, but is otherwise identical. Here dramatizes by superimposing one on the other. ![file] , 
 Clockwise here from upper left: - Fig 7A from [Ahmad et al (2018)] .  The cumulative percentage release of Eugenol from EUG-NE as compared to pure Eugenol (reproduced as Fig. 5 in [Ahmad et al (2019)] ,  The cumulative percentage release of Eugenol from EUG ). - Fig. 2a from [Ahmad et al (2018b)] .  In vitro release profile of EUG-solution, EUG-loaded-PCL-NPs and CS-coated-EUG-loaded-PCL-NPs performed by using dialysis bag method, revealing sustained release pattern of EUG-loaded-PCL-NPs and CS-coated-EUG-loaded-PCL-NPs . - **Fig. 5A from [Ahmad et al (2019a)] **.  In vitro release profile of DAUNu2013S, DAUNu2013loadedu2013PLGAu2013NPs and CSu2013DAUNu2013PLGAu2013NPs performed by using dialysis bag method, revealing sustained release pattern of DAUNu2013PLGAu2013NPs, and CSu2013DAUNu2013PLGAu2013NPs . - Fig. (5)A from [Ahmad et al (2019b)] .  In vitro release profile of GRA-solution, GRA-loaded-PCL-NPs and CS-coated-GRA-loaded-PCL-NPs performed by using dialysis bag method, revealing sustained release pattern of GRA-loaded-PCL-NPs and CS-coated-GRA-loaded-PCL-NPs . - Fig 6a from [Ahmad et al (2019c)] .  The cumulative percentage release of curcumin from Cur-SNEDDS as compared to pure curcumin. - Fig 5A from [Ahmad et al (2020)] .  In vitro release profile of CTH-S, CTHu2013loadedu2013PLGAu2013NPs and Chitosan-coated-CTHu2013loadedu2013PLGAu2013NPs performed by using dialysis bag method, revealing sustained release pattern of CTHu2013loadedu2013PLGAu2013NPs and Chitosan-coated- CTHu2013loadedu2013PLGAu2013NPs (Temp was set at 37u202fu00b0C, meanu202fu00b1u202fSD, nu202f=u202f3) at pH 7.4 (reproduced as Fig 8A in [Ahmad et al (2020a)] ). - Fig 6 from [Ahmad et al (2020b)] ,  the %age-cumulative-release of 5-FU from 5-FU-NE and 5-FU-NE-Gel when it compared with pure 5-FU-S . - Fig. 5a from [Ahmad et al (2020c)] .  In vitro release profile of THQ-S, and THQ-loaded-PLGA-NPs performed by using dialysis bag method, revealing sustained release pattern of THQ-PLGA-NPs . ![file] All 8 superimposed: ![file] Are there any nanopreparations with **different** pharmacokinetics? I am also impressed by the similarity of the release profiles of pure Eugenol, Daunorubicin, Glycyrrhizic Acid, curcumin, catechin, 5-FU and Thymoquinone, despite their different solubilities, etc.. ,