A Chitosan-PLGA based catechin hydrate nanoparticles used in targeting of lungs and cancer treatment
Authors: Hassan Mohammed Ali Almatar
Niyaz Ahmad
Taysser Mohammed Buheazah
Hussain Salman AlHomoud
Md Aftab Alam
Ridha Abdullah Alrasheed
Hassan Ali Al-Nasif
Rizwan Ahmad
Abdullah Sami Al-Ramadan
Journal: Saudi Journal of Biological Sciences (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ANOVA, analysis of variance; AUC, area under curve; Apoptosis; CC, calibration curve; CH-S, catechin-hydrate-suspension
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., Department of Natural Products and Alternative Medicine, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.

Abstract:  Objective: To prepare a novel Chitosan (CS)-coated-PLGA-NPs of catechin hydrate (CTH) and to improve lungs bioavailability via direct nose to lungs-delivery for the comparative assessment of a pulmokinetics study by the first-time UHPLC-MS/MS developed method in the treatment of lungs cancer via anticancer activities on H1299 lung cancer cells. Material and methods: PLGA-NPs was prepared by solvent evaporation (double emulsion) method followed by coated with chitosan (CS) and evaluated based on release and permeation of drug, a comparative pulmokinetics study with their anticancer activities on H1299 lung cancer cells. Results: The particle size, PDI and ZP of the optimized CAT-PLGA-NPs and CS-CAT-PLGA-NPs were determined 124.64 ¬± 12.09 nm and 150.81 ¬± 15.91 nm, 0.163 ¬± 0.03 and 0.306 ¬± 0.03, -3.94 ¬± 0.19 mV and 26.01 ¬± 1.19 mV respectively. Furthermore, higher entrapment efficiency was observed for CS-CAT PLGA NPs. The release pattern of the CS-CAT-PLGA NPs was found to favor the release of entrapped CAT within the cancer microenvironment. CS-CAT-PLGA-NPs exposed on H1299 cancer cells upto 24.0 h was found to be higher cytotoxic as compared to CAT-solution (CAT-S). CS-CAT-PLGA-NPs showed higher apoptosis of cancer cells after their exposure as compared to CAT-S. CS-CTH-PLGA-NPs showed tremendous mucoadhesive-nature as compared to CTH-S and CS-CTH-PLGA NPs by retention time (RT) of 0.589 min, and m/z of 289.21/109.21 for CTH alongwith RT of 0.613 min and m/z of 301.21/151.21 was found out for IS (internal standard), i.e. Quercetin). Likewise, for 1-1000 ng mL-1 (linear range) of % accuracy (92.01-99.31%) and %CV (inter &amp; intra-day, i.e. 2.14-3.33%) was determined. The improved Cmax with AUC0-24 was observed extremely significant (p &lt; 0.001) via i.n. as compared oral and i.v. in the wistar rat's lungs. The CS-approach was successfully designed and safely delivered CAT to the lungs without causing any risk. Conclusion: CS-CTH-PLGA-NPs were showed a significant role (p &lt; 0.001) for the enhancement of lungs-bioavailability and potentially promising approach to treat lung cancers. CS-CTH-PLGA-NPs did not cause any toxicity, it showed safety and have no obvious toxic-effects on the rat's lungs and does not produce any mortality followed by no abnormal findings in the treated-rats. 

Retracted: No

PubPeer comments:
 Figure 7. Flow cytometric dot plots of annexin V PI staining are shown in (A) untreated H1299 cells (Control) (B) H1299 cells treated with CTH-S (C) H1299 cells treated with CSCTH-PLGA-NPs.  Unexpected coincidences in (B) and (C).  , 
 #1 These images were provided by technician. , 
 Fortunately the paper is stll  In Press , with only the  Journal Pre-proof available at the publisher s website, so there is time to retrieve the correct data and replace the figure if this is necessary. , 
 #2 Dr. Ahmad: A clarifying question, do you agree with the concern in #1 and are providing an explanation as to how it happened, or do you disagree with the concern about the apparent anomalies with the figure? , 
 *[right]* Fig 3(B),  transmission electron microscopy (TEM) [B] images of CS-coated-CH-loaded-PLGA-NPs . *[left]* Fig 2(B) from [Ahmad et al (2016)] ,  Transmission Electron Microscopy (TEM) ... images of Rutin loaded Chitosan Nanoparticles .  Same image, different materials. , 
 #5 Is it just me, or do the scale bars in *either* figure not fit the indicated sizes at all? , 
 Fig 3A.  Scanning electron microscopy (SEM) [A] ... images of CS-coated-CH-loaded-PLGA-NPs. :  Fig 5A from [Ahmad et al (2020)] .  Scanning electron microscopy (SEM) (A)... images of CS-coatedu2013CH-loadedu2013PLGAu2013NPs.  Scale bars are not compatible. , 
 #3 * Fortunately the paper is stll  In Press , with only the  Journal Pre-proof available at the publisher s website, so there is time to retrieve the correct data and replace the figure if this is necessary. * It is gratifying to see that the advice was followed, and the Figure 7 in the final version does not display the problematic raw data, only summary statistics.  , 
 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 .  All 8 superimposed:  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.. ,