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  • Title: Physicochemical characterization, in vitro, and in vivo evaluation of indomethacin-loaded nanocarriers self-assembled by amphiphilic polyphosphazene.
    Author: Zhang JX, Li SH, Li XH, Qiu LY, Li XD, Li XJ, Jin Y, Zhu KJ.
    Journal: J Biomed Mater Res A; 2008 Sep 15; 86(4):914-25. PubMed ID: 18067189.
    Abstract:
    Copolymeric nanocarriers assembled by amphiphilic polyphosphazene bearing poly(N-isopropylacrylamide) (PNIPAAm) and ethyl glycinate (EtGly) as substitutes, were investigated as drug vehicles for indomethacin (IND). The physicochemical characteristics of the novel nanocontainers were studied, including lower critical solution temperature (LCST), critical micelle concentration (CMC) and drug loading capacity. LCST measurements revealed that copolymer is more sensitive to the introduction of salts into aqueous solution compared with homopolymer. A significant decrease in CMC was observed when the temperature increased above LCST. As evidenced by transmission electron microscopy (TEM) measurement, morphological transformation from multicompartment into spherical nanoparticles was observed when nanocarriers with higher IND content were concerned. In vitro release tests suggested that IND-loaded nanocontainers exhibited pH dependent release profiles. In vivo pharmacokinetic study after subcutaneous administration provided a relatively sustained release behavior. Additionally, compared with free drug solution at the same dose, IND concentration in rat plasma showed a prolonged retention in experimental group treated with IND-loaded micelles. In vivo pharmacodynamic study based on both carrageenan-induced acute and complete Freund's adjuvant (CFA) induced adjuvant-arthritis models indicated that sustained therapeutic efficacy could be achieved through intraarticular injection of IND-loaded micelles. Most importantly, local delivery of IND can avoid the severe gastrointestinal stimulation, which is frequently associated with oral administration.
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