TY - JOUR
T1 - Multidomain drug delivery systems of β-casein micelles for the local oral co-administration of antiretroviral combinations
AU - Singh Chauhan, Prakram
AU - Abutbul Ionita, Inbal
AU - Moshe Halamish, Hen
AU - Sosnik, Alejandro
AU - Danino, Dganit
N1 - Publisher Copyright:
© 2020
PY - 2021/6/15
Y1 - 2021/6/15
N2 - 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 β-casein (bCN) micelles. Encapsulation efficiency in both systems was ~100%. Cryo-transmission 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 freeze-dried without cryo/lyoprotectant, and successfully redispersed, with minor changes in morphology. Then, the ARV-loaded micelles were encapsulated within microparticles of Eudragit® 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.
AB - 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 β-casein (bCN) micelles. Encapsulation efficiency in both systems was ~100%. Cryo-transmission 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 freeze-dried without cryo/lyoprotectant, and successfully redispersed, with minor changes in morphology. Then, the ARV-loaded micelles were encapsulated within microparticles of Eudragit® 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.
KW - Combination therapy
KW - antiretrovirals
KW - darunavir
KW - efavirenz and ritonavir
KW - β-casein micelles
KW - colloidal dispersion
KW - cryo-TEM
KW - nanoparticle-in-microparticle delivery system (NiMDS)
UR - http://www.scopus.com/inward/record.url?scp=85101647161&partnerID=8YFLogxK
U2 - 10.1016/j.jcis.2020.12.021
DO - 10.1016/j.jcis.2020.12.021
M3 - 文章
C2 - 33652169
SN - 0021-9797
VL - 592
SP - 156
EP - 166
JO - Journal of Colloid and Interface Science
JF - Journal of Colloid and Interface Science
ER -
