Rifampicin-Loaded ‘Flower-Like’ Polymeric Micelles for Enhanced Oral Bioavailability in An Extemporaneous Liquid Fixed-Dose Combination with Isoniazid

Abstract

Overall results highlight the potential of this nanotechnology platform to develop an extemporaneous liquid RIF/INH fixed-dose combination suitable for pediatric administration.

Novel nelfinavir mesylate loaded d -α-tocopheryl polyethylene glycol 1000 succinate micelles for enhanced pediatric anti HIV therapy: In vitro characterization and in vivo evaluation

“…Thereafter the improvement on AUC 0-24 values for the micellar systems could be related with the ability of the NFV-loaded nanocarrier (D h : 5.6 nm) to diffuse though the mucus barrier, reaching the intestinal mucosa and promoting NFV absorption. These results are in good concordance with previously investigations where an enhanced oral bioavailability of a poorly-water soluble drug was observed after its encapsulation within nano-sized micelles [39,[41][42][43]. Interestingly, TPGS has been reported as a potent inhibitor of P-gp [22] and NFV results a P-gp substrate as other IP drugs [11,14].…”

“…The release from polymeric micelles is a complex process that involves different mechanisms such as diffusion of drug molecules, polymer chain relaxation and erosion [39]. In the present study, the mathematical analysis comprised the fitting to zero order, firstorder and Higuchi model.…”

“…Another interesting point is the hydrodynamic diameter of the TPGS micelles employed to encapsulate NFV. Nano-sized carriers with a D h < 300 nm could overcome gastrointestinal mucilliary clearance, [39] promoting drug absorption and bioavailability. Thereafter the improvement on AUC 0-24 values for the micellar systems could be related with the ability of the NFV-loaded nanocarrier (D h : 5.6 nm) to diffuse though the mucus barrier, reaching the intestinal mucosa and promoting NFV absorption.…”

Polymeric micelles for oral drug administration enabling locoregional and systemic treatments

“…This amphiphilic BAB copolymer leads to micelles with a hydrophilic corona of looped PEG blocks, which confers on the system appearance of flower petals. Rifampicin-loaded micelles displayed a spherical morphology and remarkably increased drug solubility and stability in acid medium [116]. These micelles delayed the release of rifampicin for 2 --3 h and minimized the direct contact of rifampicin with the gastric medium, which led to improved bioavailability compared with a drug suspension [116].…”

“…Amorphous PLA might better integrate/disperse the drug within the polymer matrix. Flower-like polymeric micelles of poly("-caprolactone)-bpoly(ethylene glycol)-b-poly("-caprolactone) (PCL-b-PEG-b-PCL) have been shown suitable for encapsulation of rifampicin [115,116]. This amphiphilic BAB copolymer leads to micelles with a hydrophilic corona of looped PEG blocks, which confers on the system appearance of flower petals.…”