Multidomain drug delivery systems of β-casein micelles for the local oral co-administration of antiretroviral combinations

JOURNAL OF COLLOID AND INTERFACE SCIENCE

卷:592

Article

Chauhan, Prakram Singh¹  Ionita, Inbal Abutbul¹  Halamish, Hen Moshe²  Sosnik, Alejandro²  Danino, Dganit^1,3 

[1] Technion Israel Inst Technol, Fac Biotechnol & Food Engn, CryoEM Lab Soft Matter, IL-3200003 Haifa, Israel

[2] Technion Israel Inst Technol, Dept Mat Sci & Engn, Lab Pharmaceut Nanomat Sci, IL-3200003 Haifa, Israel

[3] Guangdong Technion Israel Inst Technol, Shantou 515063, Guangdong, Peoples R China

关键词: Combination therapy;    Antiretrovirals;    Darunavir, efavirenz and ritonavir;    beta-casein micelles (bCN);    Colloidal dispersion;    cryo-TEM;    Nanoparticle-in-microparticle delivery system (NiMDS);   

DOI  :  10.1016/j.jcis.2020.12.021

来源: Elsevier

【 摘 要 】

The antiretroviral (ARV) cocktail revolved the treatment of the human immunodeficiency virus (HIV) infection. Drug combinations have been also tested to treat other infectious diseases, including the recent coronavirus disease 2019 (COVID-19) outbreak. To simplify administration fixed-dose combinations have been introduced, however, oral anti-HIV therapy still struggles with low oral bioavailability of many ARVs. This work investigated the co-encapsulation of two clinically relevant ARV combinations, tipranavir (TPV):efavirenz (EFV) and darunavir (DRV):efavirenz (EFV):ritonavir (RTV), within the core of b-casein (bCN) micelles. Encapsulation efficiency in both systems was similar to 100%. Cryotransmission electron microscopy and dynamic light scattering of the ARV-loaded colloidal dispersions indicate full preservation of the spherical morphology, and x-ray diffraction confirm that the encapsulated drugs are amorphous. To prolong the physicochemical stability the formulations were freezedried without cryo/lyoprotectant, and successfully redispersed, with minor changes in morphology. Then, the ARV-loaded micelles were encapsulated within microparticles of Eudragit (R) L100, which prevented enzymatic degradation and minimized drug release under gastric-like pH conditions in vitro. At intestinal pH, the coating polymer dissolved and released the nanocarriers and content. Overall, our results confirm the promise of this flexible and modular technology platform for oral delivery of fixed dose combinations. (C) 2020 Published by Elsevier Inc.

【 授权许可】

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