title: Hyaluronic Acid-Tocopherol Succinate-Based Self-Assembling Micelles for Targeted Delivery of Rifampicin to Alveolar Macrophages.
abstract: We developed a target drug delivery system for the treatment of tuberculosis using rifampicin (RIF) incorporated into hyaluronic acid-tocopherol succinate (HA-TS) micelles. The RIF-HA-TS micelles were physicochemically characterized and the cellular uptake of RIF-HA-TS micelles on murine alveolar macrophage MH-S cells was investigated. Furthermore, the cytokine secreting activities of the alveolar macrophages after treatment with RIF-HA-TS micelles were evaluated. The results of the studies indicate that (i) mean particle size of HA-TS micelles was in the range of 212-294.6 nm depending on the degree of substitution (DS) of the hydrophobic moiety. The incorporated RIF was sustained released from RIF loaded HA-TS micelles (ii) cellular uptake of RIF-HA-TS micelles was dose and energy dependent (iii) RIF-HA-TS micelles had a significant uptake in comparison to free RIF, with the highest uptake at 12 h (iv) RIF-HA-TS micelles were taken up into cells via phygocytosis as well as CD44 receptor-mediate endocytosis (v) beside E. coli lipopolysccharide (LPS), HA-TS micelles also could activate MH-S cells, which improved the RIF-HA-TS uptake (vi) RIF-HA-TS micelles induced higher concentration of Th1 cytokines than free drug, which will help to enhance the anti-tuberculosis activity. The results of the current studies demonstrate the feasibility of targeting macrophages and the possibility of using the HA-TS micelles for tuberculosis treatment.
authors: Yuan
authors: Y
authors: Gao
authors: Muhammad Khan
authors: MK
authors: Sarfraz
authors: Sophie-Dorothee
authors: SD
authors: Clas
authors: Wilson
authors: W
authors: Roa
authors: Raimar
authors: R
authors: Löbenberg
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004058:Diffusion; D006820:Hyaluronic Acid / Q000737:chemistry*; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008823:Micelles; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D010316:Particle Size; D012293:Rifampin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D024502:alpha-Tocopherol / Q000737:chemistry*
chemical_list: D000995:Antitubercular Agents; D016207:Cytokines; D003692:Delayed-Action Preparations; D008823:Micelles; D053769:Nanocapsules; D006820:Hyaluronic Acid; D024502:alpha-Tocopherol; D012293:Rifampin