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

• Published in: Artificial cells, nanomedicine, and biotechnology Vol. 46; no. S3; pp. 1204 - 1214
• Main Authors: Ali, Imdad, Rehman, Jawad ur, Ullah, Shafi, Imran, Muhammad, Javed, Ibrahim, El-Haj, Babiker M., Saad Ali, Heyam, Arfan, Muhammad, Shah, Muhammad Raza
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2018; Taylor & Francis Ltd
• Subjects: Administration, Oral; Amphotericin B; Amphotericin B - chemistry; Amphotericin B - pharmacokinetics; Amphotericin B - pharmacology; Animals; Atomic force microscopes; Atomic force microscopy; Bioavailability; Biocompatibility; Cancer; Cell Line, Tumor; Charge efficiency; Chemical synthesis; Computer simulation; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug Carriers - pharmacology; Drug delivery; Drug delivery systems; Entrapment; Fourier transforms; High-performance liquid chromatography; Humans; Hydrophobicity; Infrared spectroscopy; Lipophilic; Macrocycle; Mice; Micelles; Nanoparticles - chemistry; Nanoparticles - therapeutic use; NIH 3T3 Cells; NMR; Nuclear magnetic resonance; Pharmacokinetics; Pharmacology; Rabbits; Self-assembly; Spectrometry; Surface charge; Tumor cell lines; Vesicles; vesicles formation; vesicles formation; amphotericin B; drug delivery; biocompatibility; Macrocycle
• ISSN: 2169-1401; 2169-141X
• DOI: 10.1080/21691401.2018.1536061

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 1   H 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.