Preliminary investigation of novel tetra-tailed macrocycle amphiphile based nano-vesicles for amphotericin B improved oral pharmacokinetics.

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ID: 83600
2018
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Abstract
Supramolecular macrocycles-based drug delivery systems are receiving wider recognition due to their self-assembly into nanostructures with unique characteristics. This study reports synthesis of resorcinarene-based novel and biocompatible amphiphilic supramolecular macrocycle that self-assembles into nano-vesicular system for Amphotericin B (Am-B) delivery, a model hydrophobic drug. The macrocycle was synthesized through a two-step reaction and was characterized with 1H NMR and mass spectrometric techniques. Its biocompatibility was assessed in cancer cell lines, blood and animals. Its critical micelle concentration (CMC) was determined using UV spectrophotometer. Am-B loaded in novel macrocycle-based vesicles were examined according to their shape, size, surface charge, drug entrapment efficiency and excepients compatibility using atomic force microscope (AFM), Zetasizer, HPLC and FT-IR spectroscopy. Drug-loaded vesicles were also investigated for their in-vitro release, stability and in-vivo oral bioavailability in rabbits. The macrocycle was found to be nontoxic against cancer cells, haemo-compatible and safe in mice and revealed lower CMC. It formed mono-dispersed spherical shape vesicles of 174.4 ± 3.78 nm in mean size. Vesicles entrapped 92.05 ± 4.39% drug and were stable upon storage with gastric-simulated fluid and increased the drug oral bioavailability in rabbits. Results confirmed novel macrocycle as biocompatible vesicular nanocarrier for enhancing the oral bioavailability of lipophilic drugs.
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Authors Ali, Imdad;Rehman, Jawad Ur;Ullah, Shafi;Imran, Muhammad;Javed, Ibrahim;El-Haj, Babiker M;Saad Ali, Heyam;Arfan, Muhammad;Shah, Muhammad Raza;
Journal artificial cells, nanomedicine, and biotechnology
Year 2018
DOI
10.1080/21691401.2018.1536061
URL
Keywords
drug delivery biocompatibility amphotericin b macrocycle vesicles formation

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