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• W2095362233 abstract "The objective of this study was to develop poly(lactic-co-glycolic acid) (PLGA) injectable implants (i.e., millicylinders) with microencapsulated N-acetylcysteine (NAC) for site-specific controlled NAC release, for potential chemopreventive applications in persons with previously excised head and neck cancers. PLGA 50:50 (i.v. = 0.57 dl/g) implants with 1–10 wt% NAC free acid or 10 wt% NAC salts (NAC–Na+, NAC–Mg2+ and NAC–Ca2+) were prepared by solvent extrusion and/or fluid energy micronization (FEM) methods. X-ray diffraction (XRD), scanning electron microscopy (SEM), and differential scanning calorimetry (DSC) studies were performed to evaluate the physical mixing of NAC with PLGA. PLGA implant degradation was studied by kinetics of polymer molecular weight decline (gel permeation chromatography) and mass loss. Release studies were conducted in N2 purged PBS (pH 7.4) at 37°C in evacuated and sealed ampoules. NAC was quantified by HPLC at 210 nm. XRD, SEM and DSC studies indicated that NAC had dissolved in the polymer phase at 1–3.5% w/w loading, but became discretely suspended in the polymer at 6–10% w/w. Initial burst and long-term release rate increased with increased drug loading, and release was uncharacteristically rapid at higher loading (6–10% w/w). The cause of the rapid release was linked to extensive plasticization, matrix porosity and general acid catalysis of PLGA degradation caused by the NAC free acid. PLGA millicylinders loaded with 10% w/w NAC–Ca2+ and NAC–Mg2+salts exhibited reduced burst (34 vs 13–22% release within a day of incubation for NAC free acid vs NAC–Ca2+ and NAC–Mg2+salts, respectively) and slow and continuous complete release over 4 weeks without significant NAC-catalyzed degradation of PLGA. Release of NAC from NAC–Ca2+/PLGA implant was slower than that of NAC–Mg2+/PLGA consistent with the lower solubility of the former salt. NAC with its free thiol was rapidly converted to its cystine dimer in the presence of molecular oxygen. PLGA released samples in sealed and evacuated ampoules indicated >80% parent NAC remaining after the 1 month release analysis irrespective of initial NAC free acid and salt forms. By encapsulating the NAC–Mg2+ and NAC–Ca2+ salts in PLGA implants, the high initial burst, short release duration, and the general acid catalysis caused by the NAC free acid were each prevented and 1-month slow and continuous release was attained with minimal instability of the free thiol group." @default.
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• W2095362233 date "2007-09-22" @default.
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• W2095362233 title "Formulation and Characterization of Injectable Poly(dl-lactide-co-glycolide) Implants Loaded with N-Acetylcysteine, a MMP Inhibitor" @default.
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• W2095362233 doi "https://doi.org/10.1007/s11095-007-9430-1" @default.
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