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AAPS PharmSciTech

, Volume 19, Issue 7, pp 3152–3164 | Cite as

Amphotericin B Loaded Chitosan Nanoparticles: Implication of Bile Salt Stabilization on Gastrointestinal Stability, Permeability and Oral Bioavailability

  • Sanyog Jain
  • Chamala Siva Kumar Reddy
  • Rajan Swami
  • Varun Kushwah
Research Article

Abstract

Through current investigation, we presented a lucrative way to formulate amphotericin B loaded bile salt stabilized carbohydrate polymer i.e. chitosan nanoparticles (NPs) for enhancing gastrointestinal stability of NPs thereby increasing the oral bioavailability of the drug. NPs were prepared using ionic gelation method, and stabilized using bile salt to provide gastric pH stability to chitosan NPs. NPs were optimized on different parameters such as particle size, encapsulation efficiency and estimated for their in vitro and in vivo performance. Developed NPs presented a higher stability in gastrointestinal milieu, reduced haemolytic toxicity and significantly higher uptake in Caco-2 cell lines followed by increased bioavailability as compared to naive drug, marketed formulation i.e. Fungizone® and uncoated chitosan NPs. Biochemical parameters and histology further substantiated the lower toxicity. In nutshell, the present research explored the bioadhesive and higher uptake potential of cationic carbohydrate polymer at the same time along with bile salts for stabilization of NPs in gastric milieu.

KEY WORDS

amphotericin B chitosan bile salts oral bioavailability GI stability nephrotoxicity 

Abbreviations

AmB

Amphotericin B

AmB-CSCA NPs

AmB loaded bile salt stabilized chitosan nanoparticles

ANOVA

Analysis of variance

AUC

Area under the curve

BUN

Blood urea nitrogen

CA

Sodium cholate

CS

Chitosan

GI

Gastrointestinal

HPLC

High-performance liquid chromatography

kD

Kilo dalton

NPs

Nanoparticles

PDI

Polydispersity index

RBC

Red blood cells

RITC

Rhodamine isothiocyanate

SEM

Scanning electron microscopy

SGF

Simulated gastric fluid

SIF

Simulated intestinal fluid

SLS

Sodium lauryl sulphate

TEM

Transmission electron microscope

TPP

Tripolyphosphate

Notes

Acknowledgments

The authors are thankful to Director, NIPER for providing the necessary infrastructure and facilities and Department of Science & Technology (DST), Government of India, New Delhi, and financial support. Rajan Swami is grateful to Science and Engineering Research Board (SERB), DST, GOI, New Delhi, for providing research fellowship. Varun Kushwah is appreciative to CSIR, GOI, New Delhi, for providing fellowships.

Compliance with Ethical Standards

Conflict of Interest

The authors report no financial interest that might pose a potential, perceived, or real conflict.

Supplementary material

12249_2018_1153_MOESM1_ESM.docx (25 kb)
ESM 1 (DOCX 24.8 kb)

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Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Sanyog Jain
    • 1
  • Chamala Siva Kumar Reddy
    • 1
  • Rajan Swami
    • 1
  • Varun Kushwah
    • 1
  1. 1.Centre for Pharmaceutical Nanotechnology, Department of PharmaceuticsNational Institute of Pharmaceutical Education and Research (NIPER)S.A.S. Nagar (Mohali)India

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