Oral Delivery of Anti-Parasitic Agent-Loaded PLGA Nanoparticles: Enhanced Liver Targeting and Improved Therapeutic Effect on Hepatic Alveolar Echinococcosis

被引：7

作者：

Li, Jun ^{[1
]}

Yang, Yangyang ^{[2
]}

Han, Xiumin ^{[3
]}

Li, Jing ^{[2
]}

Tian, Mengxiao ^{[1
]}

Qi, Wenjing ^{[1
]}

An, Huniu ^{[3
]}

Wu, Chuanchuan ^{[1
]}

Zhang, Yao ^{[1
]}

Han, Shuai ^{[4
]}

Duan, Liping ^{[4
]}

Wang, Weisi ^{[4
]}

Zhang, Wenbao ^{[1
]}

机构：

[1] Xinjiang Med Univ, State Key Lab Pathogenesis Prevent & Treatment Hig, Clin Med Res Inst, Affiliated Hosp 1, Urumqi, Xinjiang, Peoples R China

[2] East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai, Peoples R China

[3] Qinghai Prov Peoples Hosp, Xining, Qinghai, Peoples R China

[4] Chinese Ctr Dis Control & Prevent, Natl Inst Parasit Dis, WHO Collaborating Ctr Trop Dis, NHC Key Lab Parasite & Vector Biol, Shanghai, Peoples R China

来源：

INTERNATIONAL JOURNAL OF NANOMEDICINE | 2023年 / 18卷

基金：

中国国家自然科学基金;

关键词：

alveolar echinococcosis; Echinococcus multilocularis; PLGA; nanoparticles; liver targeting; oral administration; IN-VIVO EFFICACIES; CARBAZOLE AMINOALCOHOLS; ALBENDAZOLE TREATMENT; VITRO; FORMULATION; INHIBITORS; OUTCOMES; BURDEN;

D O I：

10.2147/IJN.S397526

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Background: Alveolar echinococcosis (AE) is a lethal parasitic disease caused by infection with the metacestode of the dog/fox tapeworm Echinococcus multilocularis, which primarily affects the liver. Although continued efforts have been made to find new drugs against this orphan and neglected disease, the current treatment options remain limited, with drug delivery considered a likely barrier for successful treatment.Methods: Nanoparticles (NPs) have gained much attention in the field of drug delivery due to their potential to improve delivery efficiency and targetability. In this study, biocompatible PLGA nanoparticles encapsulating a novel carbazole aminoalcohol anti-AE agent (H1402) were prepared to promote the delivery of the parent drug to liver tissue for treating hepatic AE.Results: H1402-loaded nanoparticles (H1402-NPs) had a uniform spherical shape and a mean particle size of 55 nm. Compound H1402 was efficiently encapsulated into PLGA NPs with a maximal encapsulation efficiency of 82.1% and drug loading content of 8.2%. An in vitro uptake assay demonstrated that H1402-NPs rapidly penetrated the in vitro cultured pre-cyst wall and extensively accumulated in the pre-cysts of E. multilocularis within only 1 h. The biodistribution profile of H1402-NPs determined through ex vivo fluorescence imaging revealed significantly enhanced liver distribution compared to unencapsulated H1402, which translated to improved therapeutic efficacy and reduced systemic toxicity (especially hepatotoxicity and cytotoxicity) in a hepatic AE murine model. Following a 30-day oral regimen (100 mg/kg/day), H1402-NPs significantly reduced the parasitic burden in both the parasite mass (liver and metacestode total weight, 8.8%) and average metacestode size (89.9%) compared to unmedicated infected mice (both p-values < 0.05); the treatment outcome was more effective than those of albendazole-and free H1402-treated individuals.Conclusion: Our findings demonstrate the advantages of encapsulating H1402 into PLGA nanoparticles and highlight the potential of H1402-NPs as a promising liver-targeting therapeutic strategy for hepatic AE.

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页码：3069 / 3085

页数：17