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Development of Novel Octanoyl Chitosan Nanoparticles for Improved Rifampicin Pulmonary Delivery: Optimization by Factorial Design

Petkar, KC, Chavhan, S, Kunda, N, Saleem, IY, Somavarapu, S, Taylor, KMG and Sawant, KK (2018) Development of Novel Octanoyl Chitosan Nanoparticles for Improved Rifampicin Pulmonary Delivery: Optimization by Factorial Design. AAPS PharmSciTech, 19 (4). pp. 1758-1772. ISSN 1530-9932

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Abstract

A novel hydrophobic chitosan derivative, octanoyl chitosan (OC) with improved organic solubility was synthesized, characterized, and employed for the preparation of rifampicin (Rif) encapsulated nanoparticle formulations for pulmonary delivery. OC was characterized to confirm acyl group substitution and cytotoxicity in A549 epithelial lung cells. OC nanoparticles were produced by the double emulsion solvent evaporation technique without cross-linking and characterized for particle size distribution, morphology, crystallinity, thermal stability, aerosol delivery, and drug release rate. OC was successfully synthesized with substitution degree of 44.05 ± 1.75%, and solubility in a range of organic solvents. Preliminary cytotoxicity studies of OC showed no effect on cell viability over a period of 24 h on A549 cell lines. OC nanoparticles were optimized using a 32full factorial design. An optimized batch of OC nanoparticles, smooth and spherical in morphology, had mean hydrodynamic diameter of 253 ± 19.06 nm (PDI 0.323 ± 0.059) and entrapment efficiency of 64.86 ± 7.73% for rifampicin. Pulmonary deposition studies in a two-stage impinger following aerosolization of nanoparticles from a jet nebulizer gave a fine particle fraction of 43.27 ± 4.24%. In vitro release studies indicated sustained release (73.14 ± 3.17%) of rifampicin from OC nanoparticles over 72 h, with particles demonstrating physical stability over 2 months. In summary, the results confirmed the suitability of the developed systems for pulmonary delivery of drugs with excellent aerosolization properties and sustained-release characteristics. © 2018, American Association of Pharmaceutical Scientists.

Item Type: Article
Additional Information: This is a post-peer-review, pre-copyedit version of an article published in AAPS PharmSciTech. The final authenticated version is available online at: http://dx.doi.org/10.1208/s12249-018-0972-9
Uncontrolled Keywords: 1115 Pharmacology And Pharmaceutical Sciences
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Springer
Date Deposited: 13 Nov 2018 10:03
Last Modified: 01 Apr 2019 13:27
DOI or Identification number: 10.1208/s12249-018-0972-9
URI: http://researchonline.ljmu.ac.uk/id/eprint/9068

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