AAPS PharmSciTech

, Volume 19, Issue 4, pp 1758–1772 | Cite as

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

  • Kailash C. Petkar
  • Sandip Chavhan
  • N. Kunda
  • I. Saleem
  • S. Somavarapu
  • Kevin M. G. Taylor
  • Krutika K. Sawant
Research Article


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 32 full 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.


octanoyl chitosan hydrophobic chitosan rifampicin factorial design tuberculosis 



The authors would like to thank Mr. David McCarthy (UCL) for SEM images.

Funding information

One of the authors, Dr. Kailash C. Petkar would like to thank the Commonwealth Commission, UK, and UCL School of Pharmacy, London, for providing financial assistance.

Compliance with Ethical Standards

Conflict of Interest

The authors declare there is no conflict of interest.

Supplementary material

12249_2018_972_MOESM1_ESM.doc (134 kb)
ESM 1 (DOC 133 kb)


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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Kailash C. Petkar
    • 1
    • 2
  • Sandip Chavhan
    • 1
  • N. Kunda
    • 3
  • I. Saleem
    • 3
  • S. Somavarapu
    • 2
  • Kevin M. G. Taylor
    • 2
  • Krutika K. Sawant
    • 1
  1. 1.Faculty of Pharmacy, Department PharmaceuticsThe Maharaja Sayajirao University of BarodaVadodaraIndia
  2. 2.Department of PharmaceuticsUCL School of PharmacyLondonUK
  3. 3.School of PharmacyLiverpool John Moores UniversityLiverpoolUK

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