Abstract
Bictegravir (BIC), a newly FDA-approved integrase strand transfer inhibitor (INSTI), as a single tablet regimen has proven efficacious in treating HIV-1 and SIV viruses, with reduced resistance. BIC clinical trials have not investigated its prophylaxis potency. This study investigates the HIV prevention potency of a novel long-acting BIC nano-formulation aimed to improve adherence. Poly (lactic-co-glycolic acid) loaded BIC nanoparticles (BIC NPs) were formulated using an oil-in-water emulsion methodology. BIC NPs were <200 nm in size, with 47.9 ± 6.9% encapsulation efficiency. A novel, sensitive and high throughput LC-MS/MS method was used to estimate intracellular pharmacokinetics (PK) of BIC NPs and compared to BIC solution demonstrated prolonged intracellular BIC retention. BIC NPs safety was assessed based on cytotoxicity. Further, in-vitro prevention study of BIC NPs vs BIC solution was assessed against HIV-1 NLX and HIV-1 ADA on TZM-bl cell line and PBMCs, respectively. BIC nanoencapsulation demonstrated elevated cellular cytotoxicity concentration (CC 50 : 2.25 μM (BIC solution) to 820.4 μM (BIC NPs)] and lowers HIV-1 inhibitory concentration [EC 50 : 0.604 μM (BIC solution) to 0.0038 μM (BIC NPs)) thereby improving selectivity index (SI) from 3.7 (BIC solution) to 215,789 (BIC NP) for TZM-bl cells. Comparable results in PBMCs were obtained where BIC NPs improved SI from 0.29 (BIC solution) to 523.33 (BIC NPs). This demonstrates long-acting BIC nano-formulation with sustained drug-release potency, improved BIC cytotoxicity and enhanced HIV-1 protection compared to BIC in solution.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 83-88 |
| Number of pages | 6 |
| Journal | Antiviral Research |
| Volume | 167 |
| DOIs | |
| State | Published - Jul 1 2019 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Pharmacology
- Virology
Cite this
A potential long-acting bictegravir loaded nano-drug delivery system for HIV-1 infection : A proof-of-concept study. / Mandal, Subhra; Prathipati, Pavan Kumar; Belshan, Michael; Destache, Christopher J.
In: Antiviral Research, Vol. 167, 01.07.2019, p. 83-88.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A potential long-acting bictegravir loaded nano-drug delivery system for HIV-1 infection
T2 - A proof-of-concept study
AU - Mandal, Subhra
AU - Prathipati, Pavan Kumar
AU - Belshan, Michael
AU - Destache, Christopher J.
PY - 2019/7/1
Y1 - 2019/7/1
N2 - Bictegravir (BIC), a newly FDA-approved integrase strand transfer inhibitor (INSTI), as a single tablet regimen has proven efficacious in treating HIV-1 and SIV viruses, with reduced resistance. BIC clinical trials have not investigated its prophylaxis potency. This study investigates the HIV prevention potency of a novel long-acting BIC nano-formulation aimed to improve adherence. Poly (lactic-co-glycolic acid) loaded BIC nanoparticles (BIC NPs) were formulated using an oil-in-water emulsion methodology. BIC NPs were <200 nm in size, with 47.9 ± 6.9% encapsulation efficiency. A novel, sensitive and high throughput LC-MS/MS method was used to estimate intracellular pharmacokinetics (PK) of BIC NPs and compared to BIC solution demonstrated prolonged intracellular BIC retention. BIC NPs safety was assessed based on cytotoxicity. Further, in-vitro prevention study of BIC NPs vs BIC solution was assessed against HIV-1 NLX and HIV-1 ADA on TZM-bl cell line and PBMCs, respectively. BIC nanoencapsulation demonstrated elevated cellular cytotoxicity concentration (CC 50 : 2.25 μM (BIC solution) to 820.4 μM (BIC NPs)] and lowers HIV-1 inhibitory concentration [EC 50 : 0.604 μM (BIC solution) to 0.0038 μM (BIC NPs)) thereby improving selectivity index (SI) from 3.7 (BIC solution) to 215,789 (BIC NP) for TZM-bl cells. Comparable results in PBMCs were obtained where BIC NPs improved SI from 0.29 (BIC solution) to 523.33 (BIC NPs). This demonstrates long-acting BIC nano-formulation with sustained drug-release potency, improved BIC cytotoxicity and enhanced HIV-1 protection compared to BIC in solution.
AB - Bictegravir (BIC), a newly FDA-approved integrase strand transfer inhibitor (INSTI), as a single tablet regimen has proven efficacious in treating HIV-1 and SIV viruses, with reduced resistance. BIC clinical trials have not investigated its prophylaxis potency. This study investigates the HIV prevention potency of a novel long-acting BIC nano-formulation aimed to improve adherence. Poly (lactic-co-glycolic acid) loaded BIC nanoparticles (BIC NPs) were formulated using an oil-in-water emulsion methodology. BIC NPs were <200 nm in size, with 47.9 ± 6.9% encapsulation efficiency. A novel, sensitive and high throughput LC-MS/MS method was used to estimate intracellular pharmacokinetics (PK) of BIC NPs and compared to BIC solution demonstrated prolonged intracellular BIC retention. BIC NPs safety was assessed based on cytotoxicity. Further, in-vitro prevention study of BIC NPs vs BIC solution was assessed against HIV-1 NLX and HIV-1 ADA on TZM-bl cell line and PBMCs, respectively. BIC nanoencapsulation demonstrated elevated cellular cytotoxicity concentration (CC 50 : 2.25 μM (BIC solution) to 820.4 μM (BIC NPs)] and lowers HIV-1 inhibitory concentration [EC 50 : 0.604 μM (BIC solution) to 0.0038 μM (BIC NPs)) thereby improving selectivity index (SI) from 3.7 (BIC solution) to 215,789 (BIC NP) for TZM-bl cells. Comparable results in PBMCs were obtained where BIC NPs improved SI from 0.29 (BIC solution) to 523.33 (BIC NPs). This demonstrates long-acting BIC nano-formulation with sustained drug-release potency, improved BIC cytotoxicity and enhanced HIV-1 protection compared to BIC in solution.
UR - http://www.scopus.com/inward/record.url?scp=85064260129&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064260129&partnerID=8YFLogxK
U2 - 10.1016/j.antiviral.2019.04.007
DO - 10.1016/j.antiviral.2019.04.007
M3 - Article
C2 - 30991088
AN - SCOPUS:85064260129
VL - 167
SP - 83
EP - 88
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
ER -