Abstract
Oral delivery of amphotericin B (AmpB) is desirable because it provides a more patient-friendly mode of administration compared to the current delivery approach akin with the marketed AmpB formulations. The goal of the study was to investigate the pharmacokinetics and tissue distribution of orally administered chitosan-coated AmpB-loaded nanostructured lipid carriers (ChiAmpB NLC) administered to Sprague Dawley rats at a dose of 15 mg/kg. Orally administered ChiAmpB NLC resulted in a two-fold increase in the area under the curve (AUC0-∞) compared to the uncoated AmpB NLC and marketed Amphotret®. This enhanced bioavailability of AmpB suggests prolonged transit and retention of ChiAmpB NLC within the small intestine through mucoadhesion and subsequent absorption by the lymphatic pathway. The results show that mean absorption and residence times (MAT & MRT) were significantly higher from ChiAmpB NLC compared to the other two formulations, attesting to the mucoadhesive effect. The ChiAmpB NLC presented a lower nephrotic accumulation with preferential deposition in liver and spleen. Thus, the limitations of current marketed IV formulations of AmpB are potentially addressed with the ChiAmpB NLC in addition to utilizing this approach for targeting internal organs in visceral leishmaniasis.
Highlights
Oral administration of amphotericin B (AmpB) appeals to clinicians and patients alike because of the potential of eliminating the toxicities associated with the current mode of delivery, which is exclusively by intravenous (IV) administration
AmpB is used as the second-line therapy for visceral leishmaniasis which comes after parental administration of pentavalent antimony organic compounds which are associated with high frequency of resistance and side effects [19]
ChiAmpB nanostructured lipid carriers (NLCs) demonstrated an improvement in the oral bioavailability of
Summary
Oral administration of AmpB appeals to clinicians and patients alike because of the potential of eliminating the toxicities (notably nephrotoxicity) associated with the current mode of delivery, which is exclusively by intravenous (IV) administration. Due to the poor solubility and permeability of challenging physicochemical properties of AmpB, oral delivery of AmpB results in a meager bioavailability (< 0.3 %) which limits its therapeutic efficacy [3,4]. Poor oral absorption of AmpB has long been reported in different animal trials such as in rats [5,6], mice [7] and dogs [8]. Nanotechnology seems to be the key to unlocking some of the constraints associated with the administration of Amp orally. With the introduction of the nanotechnology, there is a ray of hope to developing a safer, yet effective oral formulation of AmpB
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