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Hyaluronic Acid-Tocopherol Succinate-Based Self-Assembling Micelles for Targeted Delivery of Rifampicin to Alveolar Macrophages

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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.
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Keywords: CYTOKINE; HYALURONIC ACID; MACROPHAGE; RIFAMPICIN; TARGETING; α-TOCOPHERYL SUCCINATE

Document Type: Research Article

Publication date: August 1, 2015

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  • Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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