Effective in vivo reactivation of HIV-1 latency reservoir via oral administration of EK-16A-SNEDDS.
Eur J Pharm Biopharm
; 201: 114353, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38885911
ABSTRACT
The latent reservoir of human immunodeficiency virus (HIV) is a major obstacle in the treatment of acquired immune deficiency syndrome (AIDS). The "shock and kill" strategy has emerged as a promising approach for clearing HIV latent reservoirs. However, current latency-reversing agents (LRAs) have limitations in effectively and safely activating the latent virus and reducing the HIV latent reservoirs in clinical practice. Previously, EK-16A was extracted from Euphorbia kansui, which had the effect of interfering with the HIV-1 latent reservoir and inhibiting HIV-1 entry. Nevertheless, there is no suitable and efficient EK-16A oral formulation for in vivo delivery and clinical use. In this study, an oral EK-16A self-nanoemulsifying drug delivery system (EK-16A-SNEDDS) was proposed to "shock" the HIV-1 latent reservoir. This system aims to enhance the bioavailability and delivery of EK-16A to various organs. The composition of EK-16A-SNEDDS was optimized through self-emulsifying grading and ternary phase diagram tests. Cell models, pharmacokinetic experiments, and pharmacodynamics in HIV-1 latent cell transplant animal models suggested that EK-16A-SNEDDS could be absorbed by the gastrointestinal tract and enter the blood circulation after oral administration, thereby reaching various organs to activate latent HIV-1. The prepared EK-16A-SNEDDS demonstrated safety and efficacy, exhibited high clinical experimental potential, and may be a promising oral preparation for eliminating HIV-1 latent reservoirs.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
HIV-1
/
Virus Latency
/
Emulsions
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Eur J Pharm Biopharm
Journal subject:
FARMACIA
/
FARMACOLOGIA
Year:
2024
Document type:
Article
Country of publication:
Netherlands