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Synergistic enhancement of parasiticidal activity of amphotericin B using copaiba oil in nanoemulsified carrier for oral delivery: an approach for non‐toxic chemotherapy
Author(s) -
Gupta Pramod K,
Jaiswal Anil K,
Asthana Shalini,
Teja B Venkatesh,
Shukla Prashant,
Shukla Minakshi,
Sagar Neeti,
Dube Anuradha,
Rath Srikanta K,
Mishra Prabhat R
Publication year - 2015
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.13149
Subject(s) - bioavailability , pharmacology , chemistry , pharmacokinetics , toxicity , amphotericin b , polyethylene glycol , liposome , drug delivery , microbiology and biotechnology , medicine , biochemistry , biology , antifungal , organic chemistry
Background and Purpose The aim of this study was to devise a nanoemulsified carrier system ( CopNEC ) to improve the oral delivery of amphotericin B ( AmB ) by increasing its oral bioavailability and synergistically enhance its antileishmanial activity with copaiba oil ( C op). Experimental Approach The AmB encapsulated NEC ( CopNEC‐AmB ) comprised of C op, d‐α‐tocopheryl polyethylene glycol 1000 succinate and phosphatidylcholine was prepared by high‐pressure homogenization method. Stability study of CopNEC‐AmB was carried out in simulated gastric fluid and simulated intestinal fluid. The CopNEC‐AmB and plain AmB were compared as regards their in vitro antileishmanial activity, pharmacokinetics, organ distribution and toxicity. Key Results The optimal CopNEC‐AmB had a small globule size, low polydispersity index, high ζ potential and encapsulation efficiency. The high resolution transmission electron microscopy illustrated spherical particle geometry with homogeny in their sizes. The optimal CopNEC‐AmB was found to be stable in gastrointestinal fluids showing insignificant changes in globule size and encapsulation efficiency. The AUC 0–48 value of CopNEC‐AmB in rats was significantly improved showing 7.2‐fold higher oral bioavailability than free drug. The in vitro antileishmanial activity of CopNEC‐AmB was significantly higher than that of the free drug as C op synergistically enhanced the antileishmanial effect of AmB by causing drastic changes in the morphology of L eishmania parasite and rupturing its plasma membrane. The CopNEC‐AmB showed significantly less haemolytic toxicity and cytotoxicity and did not change the histopathology of kidney tissues as compared with AmB alone. Conclusions and Implications This prototype CopNEC formulation showed improved bioavailability and had a non‐toxic synergistic effect on the antileishmanial activity of AmB .