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Novel injectable progesterone-loaded nanoparticles embedded in SAIB-PLGA in situ depot system for sustained drug release

[Display omitted] Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) have attracted considerable interest in the medical community as a sustained-release drug delivery system for localized treatment. However, it is currently a grand challenge to simultaneously achieve low-dose drugs, stable a...

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Bibliographic Details
Published in:International journal of pharmaceutics 2021-09, Vol.607, p.121021-121021, Article 121021
Main Authors: Cao, Zhijun, Tang, Xing, Zhang, Yu, Yin, Tian, Gou, Jingxin, Wang, Yanjiao, He, Haibing
Format: Article
Language:English
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Summary:[Display omitted] Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) have attracted considerable interest in the medical community as a sustained-release drug delivery system for localized treatment. However, it is currently a grand challenge to simultaneously achieve low-dose drugs, stable and prolonged drug release, and long-term retention circumventing uptake by macrophages. Here, we construct a solvent-exchange in-situ depot system by incorporating progesterone (PRG) loaded PLGA NPs into a sucrose acetate isobutyrate (SAIB) and PLGA matrix for the long term treatment of Assisted Reproductive Technology (ART). The results showed that different solvent and PLGA contents could affect the drug release rate of PRG NPs-SAIB-PLGA in-situ depot system (PSPIDS). When DMSO was used as solvent with the addition of 8% PLGA to the depot, PSPIDS could achieve a constant drug release with no burst for 2 weeks in vitro. After a single intramuscular injection, such PSPIDS showed higher drug concentration and AUC (6773.0 ± 348.8 μg/L·h) over the entire 7-day testing period compared with the commercial multiple-day-dosing intramuscular PRG-oil solution (1914.5 ± 180.7 μg/L·h) in vivo. Importantly, PSPIDS could be administered at a dose of 3.65 mg/kg, which was one fourth of dose required for PRG-oil solution. The results demonstrate that PRG NPs could successfully achieve both reduced administered dosage and burst release, and therefore that PSPIDS is a promising long-acting composite system for hydrophobic drugs.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2021.121021