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

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 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.

The physicochemical properties and molecular docking study of plasticized amphotericin B loaded sodium alginate, carboxymethyl cellulose, and gelatin-based films

“…This variation is attributed to the interactions of AmB with the polymers and the plasticizer. Moreover, the absence of the AmB's specific peak at 1549 cm −1 in the S2–S4 samples indicates the development of a robust electrostatic bond between the polymer and the drug [ 47 , [49] , [50] , [51] ]. The band ranging from 2875 to 3012 cm −1 is indicative of the C–H stretching vibrations.…”

Investigating the self-assembling of nicotinic hydrazide-based amphiphile into nano-range vesicles and its amphotericin B loading applications

“…The drug-loaded vesicles of synthesized nonionic surfactants NODNH-18 and NODNH-16 were prepared through the hydration of the surfactant thin film method (Ali, Rehman et al., 2018 ; Ali, Shah et al., 2018 ). Briefly, cholesterol (7 mg), surfactant NODNH-18 or NODNH-16 (15 mg), and drug (amphotericin B; 5 mg) were made soluble in a binary solvent mixture of chloroform and methanol (7 mL:4 mL).…”

Synthesis of Calix (4) Resorcinarene Based Amphiphilic Macrocycle as an Efficient Nanocarrier for Amphotericin-B to Enhance Its Oral Bioavailability

“…The hplc method development, validation, optimization and drug extraction from plasma all are present in previous published articles [41,42].…”