Polypeptidic Micelles Stabilized with Sodium Alginate Enhance the Activity of Encapsulated Bedaquiline

Abstract

The coating of polypeptidic micelles with sodium alginate is described as a strategy to improve the stability of micelles for drug delivery. Bedaquiline, approved in 2012 for the treatment of multidrug resistant tuberculosis, has been used as an example of hydrophobic drug to study the loading efficiency, the release of the encapsulated drug in different media, and the in vitro antimicrobial activity of the system. Alginate coating prevents the burst release of the drug from micelles upon dilution and leads to a sustained release in all tested media. In view of possible oral administration, the alginate coated micelles show better stability in gastric and intestinal simulated media. Notably, the encapsulated bedaquiline shows increased in vitro activity against Mycobacterium tuberculosis compared to free bedaquiline.

Sodium Alginate as a Pharmaceutical Excipient: Novel Applications of a Well-known Polymer

“…The other use of alginate in micelles was proposed by Soria-Carrera and co-workers 82 who used sodium alginate for the coating of polypeptidic micelles as a strategy to improve the stability of micelles for drug delivery. They used bedaquiline (BED) as a model drug.…”

Subcellular localization and therapeutic efficacy of polymeric micellar nanoparticles encapsulating bedaquiline for tuberculosis treatment in zebrafish

“…Preparation of unlabelled micelles: M30 and M30-BQ. M30 empty nanoparticles and loaded with BQ, M30-BQ, were prepared from ZK 30 -E 30 as published previously 29 to be used as NP-blank and NP-BQ in the experiments where fluorescent labelling was not needed.…”

“…Critical micellar concentration was measured using NileRed as solvatochromic probe with a protocol described elsewhere. 29 Transmission electron microscopy of micelles. Micelles at a concentration of 2 mg mL −1 were allowed to adsorb on carboncoated copper grids for 2 min before being washed twice for one minute with H 2 O.…”

Micellar Drug Delivery Systems Based on Natural Biopolymers

“…Block co-polypeptides, based on γ-benzyl-L-glutamic acid, ε-N-benzyloxycarbonyl-L-lysine (ZK 30 -b-BnE 30 and ZK 30 -b-BnE 60 ), were prepared by a dialysis method [129]. Bedaquiline (BQ) was used as a model drug for the treatment of multidrug resistant tuberculosis.…”