Synergistic enhancement of parasiticidal activity of amphotericin B using copaiba oil in nanoemulsified carrier for oral delivery: an approach for non‐toxic chemotherapy

Abstract

BACKGROUND AND PURPOSEThe 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 (Cop). EXPERIMENTAL APPROACHThe AmB encapsulated NEC (CopNEC-AmB) comprised of Cop, 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 RESULTSThe 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 AUC0-48 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 Cop synergistically enhanced the antileishmanial effect of AmB by causing drastic changes in the morphology of Leishmania 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 IMPLICATIONSThis prototype CopNEC formulation showed improved bioavailability and had a non-toxic synergistic effect on the antileishmanial activity of AmB.

Meta-analysis on Copaiba Oil: Its Functions in Metabolism and Its Properties as an Anti-inflammatory Agent

“…Contrary to what was thought, the oral administration of copaiba was shown to be non-toxic to rat liver when used as a carrier for amphotericin B. 14 In contrast, in another study, the results revealed that copaiba oil showed anti-inflammatory and systemic antioxidant actions in arthritic rats. These beneficial effects, however, were counterbalanced by deleterious modifications in the metabolism and morphology of hepatic cells of healthy control rats.…”

Topical Amphotericin B Semisolid Dosage Form for Cutaneous Leishmaniasis: Physicochemical Characterization, Ex Vivo Skin Permeation and Biological Activity

“…Considerable research is also being directed into the development of oral or topical formulations, as they imply greater patient compliance and fewer side effects. Chitosan has been investigated as a nanocarrier for oral administration [18], as well as an ingredient in an emulsion of nanoparticles [19]. Dermal delivery has been achieved with microneedles that generate micropores in the epidermis for the administration of an AmB solution [20].…”

Antileishmanial activity of sulphonamide nanoemulsions targeting theβ-carbonic anhydrase fromLeishmaniaspecies

“…Several studies have been demonstrated that nano-emulsified carrier systems have potential to solve problems with poor water solubility and poor membrane permeability of some drugs 45 . Moreover, the toxicity of some drugs can be reduced when they are nano-emulsified with an appropriate carrier 46–48 . Gupta et al.…”

“…Gupta et al. formulated a nano-emulsified carrier system with copaiba oil to improve the antileishmanial activity and oral bioavailability of amphotericin B 46 . They produced their NE by mixing a surfactant (TPGS, d-α-tocopheryl polyethylene glycol 1000 succinate), a co-surfactant (phosphatidyl choline (PC)), the oil and the drug, to form an O/W emulsion with particle size of 127 ± 21 nm and PDI of 0.11 ± 0.02.…”