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Drug Delivery and Translational Research

, Volume 6, Issue 4, pp 365–379 | Cite as

Improved mucoadhesion and cell uptake of chitosan and chitosan oligosaccharide surface-modified polymer nanoparticles for mucosal delivery of proteins

  • Sathish Dyawanapelly
  • Uday Koli
  • Vimisha Dharamdasani
  • Ratnesh Jain
  • Prajakta Dandekar
Research Article

Abstract

The main aim of the present study was to compare mucoadhesion and cellular uptake efficiency of chitosan (CS) and chitosan oligosaccharide (COS) surface-modified polymer nanoparticles (NPs) for mucosal delivery of proteins. We have developed poly (d, l-lactide-co-glycolide) (PLGA) NPs, surface-modified COS-PLGA NPs and CS-PLGA NPs, by using double emulsion solvent evaporation method, for encapsulating bovine serum albumin (BSA) as a model protein. Surface modification of NPs was confirmed using physicochemical characterization methods such as particle size and zeta potential, SEM, TEM and FTIR analysis. Both surface-modified PLGA NPs displayed a slow release of protein compared to PLGA NPs. Furthermore, we have explored the mucoadhesive property of COS as a material for modifying the surface of polymeric NPs. During in vitro mucoadhesion test, positively charged COS-PLGA NPs and CS-PLGA NPs exhibited enhanced mucoadhesion, compared to negatively charged PLGA NPs. This interaction was anticipated to improve the cell interaction and uptake of NPs, which is an important requirement for mucosal delivery of proteins. All nanoformulations were found to be safe for cellular delivery when evaluated in A549 cells. Moreover, intracellular uptake behaviour of FITC-BSA loaded NPs was extensively investigated by confocal laser scanning microscopy and flow cytometry. As we hypothesized, positively charged COS-PLGA NPs and CS-PLGA NPs displayed enhanced intracellular uptake compared to negatively charged PLGA NPs. Our results demonstrated that CS- and COS-modified polymer NPs could be promising carriers for proteins, drugs and nucleic acids via nasal, oral, buccal, ocular and vaginal mucosal routes.

Keywords

Chitosan Chitosan oligosaccharide Poly (d, l-lactide-co-glycolide) Nanoparticle Protein Mucosal delivery 

Notes

Acknowledgments

Mr. Sathish Dyawanapelly would like to thank Department of Biotechnology (BT/PR5372/MED/29/489/2012), Govt. of India for the fellowship. Dr. Prajakta Dandekar is thankful to Ramanujan Fellowship Grant (SR/S2/RJN-139/2011), DST, Govt. of India. Dr. Ratnesh Jain is thankful to Ramalingaswami Fellowship (BT/RLF/RE-ENTRY/51/2011), DBT, Govt. of India. The authors are grateful for the technical assistance of Maruthi Prasanna, Nishant Jain and Kireeti Kumar Kota. PURAC Biopolymers, Netherlands  and Evonik, India is acknowledged for the generous gift of PLGA. Authors are thankful to DST Nanomission (SR/NM/NS 1145/2012) for Imaging Flow Cytometer facility. Dr. Ratnesh Jain is thankful to DST-FIST (SR/FST/ETII-058/2013) for Confocal Microscopy facility.

Compliance with ethical standards

Statement of human and animal rights

‘No animal or human studies were carried out by the authors for this article.’

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

13346_2016_295_MOESM1_ESM.docx (281 kb)
ESM 1 (DOCX 280 kb)

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Copyright information

© Controlled Release Society 2016

Authors and Affiliations

  1. 1.Department of Pharmaceutical Sciences and TechnologyInstitute of Chemical TechnologyMumbaiIndia
  2. 2.Departments of Chemical EngineeringInstitute of Chemical TechnologyMumbaiIndia

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