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  • Title: Delivery of ofloxacin to the lung and alveolar macrophages via hyaluronan microspheres for the treatment of tuberculosis.
    Author: Hwang SM, Kim DD, Chung SJ, Shim CK.
    Journal: J Control Release; 2008 Jul 14; 129(2):100-6. PubMed ID: 18538437.
    Abstract:
    Microspheres containing ofloxacin (HMO) with a mean diameter of 2-5 mum were prepared by the co-spray drying of ofloxacin and the sodium salt of hyaluronic acid (hyaluronan). Recovery of lactose blends of HMO from stage II of the twin-stage impinger (TSI) reached 43%, indicating favorable delivery of the drug to the lung via inhalation. The area under the ofloxacin concentration curve from time zero to infinity (AUC) was estimated for plasma and lungs in rats following intratracheal (it), intravenous (iv), and oral (po) administration of HMO, ofloxacin microspheres (MO), and an aqueous solution of ofloxacin (OS), at an equivalent ofloxacin dose of 8 mg/kg rat. The AUC ratio between the lung and plasma for it-administered HMO was.10.9-, 9.3- and 1.8-fold greater than iv OS, po OS, and it MO, respectively, suggesting that the most efficient delivery of ofloxacin to the lung is feasible via HMO. Moreover, in vitro uptake of ofloxacin from HMO by air-surface cultured alveolar macrophages (RAW 264.7) was 2.1- and 1.7-fold higher than ofloxacin uptake from OS and MO (P<0.05). Taken together, the results of the present study demonstrate that pulmonary administration of ofloxacin via HMO would improve the treatment efficacy of ofloxacin against tuberculosis, compared to other forms of ofloxacin (OS and MO) and to other routes of administration (iv and po).
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