Aqueous core epigallocatechin gallate PLGA nanocapsules: characterization, antibacterial activity against uropathogens, and in vivo reno-protective effect in cisplatin induced nephrotoxicity

Autor: Badriyah Alotaibi, Thanaa A. El-Masry, Engy Elekhnawy, Aya H. El-Kadem, Asmaa Saleh, Walaa A. Negm, Dalia H. Abdelkader
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Drug Delivery, Vol 29, Iss 1, Pp 1848-1862 (2022)
Druh dokumentu: article
ISSN: 10717544
1521-0464
1071-7544
DOI: 10.1080/10717544.2022.2083725
Popis: Epigallocatechin-3-gallate (EGCG) was isolated from Cycas thouarsii leaves for the first time and encapsulated in aqueous core poly(lactide-co-glycolide) (PLGA) nanocapsules (NCs). This work investigates antimicrobial activity and in vivo reno-protective effects of EGCG-PLGA NCs in cisplatin-induced nephrotoxicity. A double emulsion solvent evaporation process was adopted to prepare PLGA NCs loaded with EGCG. Particle size, polydispersity index (PDI), zeta potential, percent entrapment efficiency (%EE), structural morphology, and in vitro release platform were all studied in vitro. The optimum formula (F2) with particle size (61.37 ± 5.90 nm), PDI (0.125 ± 0.027), zeta potential (–11.83 ± 3.22 mV), %EE (85.79 ± 5.89%w/w), initial burst (36.85 ± 4.79), and percent cumulative release (87.79 ± 9.84) was selected for further in vitro/in vivo studies. F2 exhibited an enhanced antimicrobial activity against uropathogens as it had lower minimum inhibitory concentration (MIC) values and a more significant impact on bacterial growth than free EGCG. Forty male adult mice were randomly allocated into five groups: control vehicle, untreated methotrexate, MTX groups treated with a daily oral dose of free EGCG, placebo PLGA NCs, and EGCG PLGA NCs (F2) for 10 days. Results showed that EGCG PLGA NCs (F2) exerted promising renoprotective effects compared to free EGCG. EGCG PLGA NCs group induced a significant decrease in kidney index, serum creatinine, kidney injury molecule-1 (KIM-1), NGAL serum levels, and pronounced inhibition of NLPR-3/caspase-1/IL/1β inflammasome pathway. It also significantly ameliorated oxidative stress and decreased NFκB, Bax expression levels. Aqueous core PLGA NCs are a promising formulation strategy that provides high polymeric protection and sustained release pattern for hydrophilic therapeutic agents.
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