Self-Assembled, Chitosan Grafted PLGA Nanoparticles for Intranasal Delivery: Design, Development and Ex Vivo Characterization

Abstract

The objective of present study was to modify the surface of Poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles (NPs) with chitosan to enhance the mucoadhesive potential of carrier system. Grafting of chitosan on PLGA surface was carried out via amide bond formation mediated by carbodiimide and confirmed by FTIR spectroscopy. Self-assembled PLGA NPs containing chlorpromazine hydrochloride were fabricated by 2³ factorial design. The improved mucoadhesive potential was confirmed by several tests including in vitro mucoadhesion study. Ex vivo permeation was satisfactory. Histopathological study on sheep nasal mucosa revealed safe mucoadhesion. They were also found to be robust on accelerated stability study.

Keywords:

• Chitosan
• Complexation
• Mucin
• Mucoadhesion
• PLGA
• Polymer grafting
• Surface modification

ACKNOWLEDGMENT

We gratefully acknowledge Torrent Pharmaceuticals Pvt. Ltd., Ahmadabad for providing gift sample of chlorpromazine hydrochloride (CPZ). The authors also thankful to Management of R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur for providing the necessary facilities to carry out this research work.

Notes

[(+1) indicates high level and (−1) low level)];.

^a These results are mean ± standard deviation. (n = 3).

^a x/m = K · Ce1/n;.

^b 1/(x/m) = a+b · 1/Ce.

x/mis mucin adsorbed, K and n are Freundlich isotherm constants, a and b are Langmuir isotherm constants, and Ce is the free mucin.

^a These results are mean ± standard deviation. (n = 3).

Y1: Particle Size, Y2: EE, R²: Regression Coefficient, SD: Standard Deviation, CV: Coefficient of Variance.

DF: Degrees of Freedom, SS: Sum of Square, MS: Mean Sum of Square and F: Fischer's ratio.