COMPARATIVE MUCOPENETRATION ABILITY OF METRONIDAZOLE LOADED CHITOSAN AND PEGYLATED CHITOSAN NANOPARTICLES
DOI:
https://doi.org/10.22159/ajpcr.2017.v10i6.17643Keywords:
Chitosan, Methoxy polyethylene glycol-grafted-chitosan, Nanoparticles, Hydroxyl propyl methyl cellulose phthalate, Ionic gelation, MucopenetrationAbstract
Objective: The objective of this study is to compare the mucopenetration ability of metronidazole loaded chitosan (CS) and pegylated CS nanoparticles.
Methods: Nanoparticles were prepared by ionic gelation technique using negatively charged pH sensitive polymer, hydroxyl propyl methyl cellulose phthalate with positively charged CS and methoxy polyethylene glycol-grafted-CS (mPEG-g-CS). mPEG-g-CS was synthesized by formaldehyde linkage method and characterized by Fourier transform infrared spectroscopy. The optimized formulations were compared for morphology, particle size, polydispersity index (PDI), entrapment efficiency, bioadhesion detachment force, in vitro and in vivo mucopenetration for CS-mPEG-g-CS nanoparticles.
Results: The morphological assessment revealed smooth spherical particles with uniform dispersions. The optimized formulations particle size was found to be 202.7±27 nm and 294.1±46 nm, zeta potential 26.94±2.4 mV and 6.0±1.3 mV. PDI 0.231 and 0.268, entrapment efficiency 79.8±5.4% and 83.6±9.7%, bio-adhesion detachment force 14.98*103 dyne/cm2 and 10.67*103 dynes/cm2, in vitro mucopenetration 78% and 98% for CS-mPEG-g-CS, respectively. The qualitative in vivo mucopenetration result confirms retention of fluorescein isothiocyanate (FITC) labeled mPEG-g-CS nanoparticles till 24 hrs.
Conclusion: Nanoparticles with lesser zeta potential and mucoadhesion showed higher mucosal penetration which is evident from FITC labeled histopathological mucus penetration test. Studies thus provided evidence that planned pharmaceutical strategies open new vistas for effective treatment of mucosal infections.
Downloads
References
Coco R, Plapied L, Pourcelle V, Jérôme C, Brayden DJ, Schneider YJ, et al. Drug delivery to inflamed colon by nanoparticles: Comparison of different strategies. Int J Pharm 2013;440(1):3-12.
Krishnaiah YS, Bhaskar Reddy PR, Satyanarayana V, Karthikeyan RS. Studies on the development of oral colon targeted drug delivery systems for metronidazole in the treatment of amoebiasis. Int J Pharm 2002;236:43-55.
Hua S, Marks E, Schneider JJ, Keely S. Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: Selective targeting to diseased versus healthy tissue. Nanomedicine 2015;11(5):1117-32.
Li X, Chen D, Le C, Zhu C, Gan Y, Hovgaard L, et al. Novel mucus-penetrating liposomes as a potential oral drug delivery system: Preparation, in vitro characterization, and enhanced cellular uptake. Int J Nanomedicine 2011;6:3151-62.
Tang BC, Dawson M, Lai SK, Wang YY, Suk JS, Yang M, et al. Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. Proc Natl Acad Sci U S A 2009;106(46):19268-73.
Lai SK, Wang YY, Hanes J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev 2009;61(2):158-71.
Lautenschläger C, Schmidt C, Lehr CM, Fischer D, Stallmach A. PEG-functionalized microparticles selectively target inflamed mucosa in inflammatory bowel disease. Eur J Pharm Biopharm 2013;85:578-86.
Sadhasivam L, Dey N, Francis AP, Devasena T. Transdermal patches of chitosan nanoparticles for insulin delivery. Int J Pharm Pharm Sci 2015;7(5):84-8.
Ruby JJ, Pandy VP. Chitosan nanoparticles as a nasal drug delivery for memantine hydrochloride. Int J Pharm Pharm Sci 2015;7(1):34-7.
Bagheri KS, Taghizadeh SM, Mirzade H. An investigation on the short-term biodegradability of chitosan with various molecular weights and degrees of deacetylation. Carbohydr Polym 2009;78:773-8.
Gan Q, Wang T, Cochrane C, McCarron P. Modulation of surface charge, particle size and morphological properties of chitosan-TPP nanoparticles intended for gene delivery. Colloids Surf B Biointerfaces 2005;44(2-3):65-73.
George M, Abraham TE. Polyionic hydrocolloids for the intestinal delivery of protein drugs: Alginate and chitosan - A review. J Control Release 2006;114(1):1-14.
Makhlof A, Tozuka Y, Takeuchi H. Design and evaluation of novel pH-sensitive chitosan nanoparticles for oral insulin delivery. Eur J Pharm Sci 2011;42(5):445-51.
Kulkarni AR, Lin YH, Liang HF, Chang WC, Hsiao WW, Sung HW. A novel method for the preparation of nanoaggregates of methoxy polyethyleneglycol linked chitosan. J Nanosci Nanotechnol 2006;6(9-10):2867-73.
Abdulkarim M, Agulló N, Cattoz B, Griffiths P, Andreas B, Borros S, et al. Nanoparticle diffusion within intestinal mucus: Three-dimensional response analysis dissecting the impact of particle surface charge, size and heterogeneity across polyelectrolyte, pegylated and viral particles. Eur J Pharm Biopharm 2015;97:230-8.
Qaqish RB, Amiji MM. Synthesis of a fluorescent chitosan derivative and its application for the study of chitosan-mucin interactions. Carbohydr Polym 1999;38:99-107.
Kerec M, Bogataj M, Mugerle B, Gasperlin M, Mrhar A. Mucoadhesion on pig vesical mucosa: Influence of polycarbophil/calcium interactions. Int J Pharm 2002;241(1):135-43.
Ramteke S, Ganesh N, Bhattacharya S, Jain NK. Amoxicillin, clarithromycin, and omeprazole based targeted nanoparticles for the treatment of H. pylori. J Drug Target 2009;17(3):225-34.
Li Y, Pei Y, Zhang X, Gu Z, Zhou Z, Yuan W, et al. PEGylated PLGA nanoparticles as protein carriers: Synthesis, preparation and biodistribution in rats. J Control Release 2001;71(2):203-11.
Suk JS, Lai SK, Wang YY, Ensign LM, Zeitlin PL, Boyle MP, et al. The penetration of fresh undiluted sputum expectorated by cystic fibrosis patients by non-adhesive polymer nanoparticles. Biomaterials 2009;30(13):2591-7.
Yang X, Zhang Q, Wang Y, Chen H, Zhang H, Gao F, et al. Self-aggregated nanoparticles from methoxy poly (ethylene glycol)-modified chitosan: Synthesis; characterization; Aggregation and methotrexate release in vitro. Colloids Surf B Biointerfaces 2008;61(2):125-31.
Lamprecht A, Schäfer U, Lehr CM. Size-dependent bioadhesion of micro-and nanoparticulate carriers to the inflamed colonic mucosa. Pharm Res 2001;18(6):788-93.
Redhead HM, Davis SS, Illum L. Drug delivery in poly (lactide-co-glycolide) nanoparticles surface modified with poloxamer 407 and poloxamine 908: In vitro characterisation and in vivo evaluation. J Control Release 2001;70(3):353-63.
Deacon MP, McGurk S, Roberts CJ, Williams PM, Tendler SJ, Davies MC, et al. Atomic force microscopy of gastric mucin and chitosan mucoadhesive systems. Biochem J 2000;348:557-63.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
