Drug development and industrial pharmacy · 2026
Cabotegravir-loaded polymeric micelles: a promising strategy for improved solubility and therapeutic outcomes.
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Vernekar Siddharth, Patil Archana S, Gaude Yadishma A, Masareddy Rajashree S
Аннотация
OBJECTIVE: To design and optimize a d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-stabilized polymeric micellar system for cabotegravir (CAB), strategically addressing its dissolution-rate and permeability constraints to potentiate oral bioavailability and maximize antiretroviral therapeutic outcomes.
SIGNIFICANCE: CAB, a potent HIV-1 integrase strand transfer inhibitor, suffers from dissolution-rate limitations and P-glycoprotein efflux, restricting oral utility. Incorporation of TPGS enables superior solubilization, enhances intestinal translocation, and circumvents efflux transporters, offering a transformative, noninvasive alternative to parenteral antiretroviral regimens while reinforcing patient adherence and therapeutic efficacy.
METHODS: CAB-loaded micelles were fabricated via the thin-film hydration technique and systematically optimized using a 32 full-factorial design by modulating TPGS concentration and rotary evaporation speed to minimize particle size (PS) and maximize drug encapsulation. The optimized formulation underwent physicochemical characterization, including PS, polydispersity index (PDI), zeta potential (ZP), and surface morphology. In vitro drug release was examined, followed by in vivo pharmacokinetic profiling in Wistar rats.
RESULTS: The optimized micellar system demonstrated a mean PS of 95.16 ± 0.12 nm, PDI of 0.411 ± 0.24, ZP of -4.72 ± 1.05 mV, and an exceptional encapsulation efficiency of 96.26 ± 1.21%. Compared to conventional CAB suspension, the TPGS-based micelles exhibited markedly enhanced dissolution kinetics and a 236.75 ± 0.74% increase in relative oral bioavailability, accompanied by prolonged systemic circulation.
CONCLUSION: TPGS-enabled micellar encapsulation significantly enhances the oral delivery profile of CAB, offering a promising, noninvasive, and patient-compliant alternative to parenteral antiretroviral regimens, potentially improving therapeutic outcomes in HIV management.
SIGNIFICANCE: CAB, a potent HIV-1 integrase strand transfer inhibitor, suffers from dissolution-rate limitations and P-glycoprotein efflux, restricting oral utility. Incorporation of TPGS enables superior solubilization, enhances intestinal translocation, and circumvents efflux transporters, offering a transformative, noninvasive alternative to parenteral antiretroviral regimens while reinforcing patient adherence and therapeutic efficacy.
METHODS: CAB-loaded micelles were fabricated via the thin-film hydration technique and systematically optimized using a 32 full-factorial design by modulating TPGS concentration and rotary evaporation speed to minimize particle size (PS) and maximize drug encapsulation. The optimized formulation underwent physicochemical characterization, including PS, polydispersity index (PDI), zeta potential (ZP), and surface morphology. In vitro drug release was examined, followed by in vivo pharmacokinetic profiling in Wistar rats.
RESULTS: The optimized micellar system demonstrated a mean PS of 95.16 ± 0.12 nm, PDI of 0.411 ± 0.24, ZP of -4.72 ± 1.05 mV, and an exceptional encapsulation efficiency of 96.26 ± 1.21%. Compared to conventional CAB suspension, the TPGS-based micelles exhibited markedly enhanced dissolution kinetics and a 236.75 ± 0.74% increase in relative oral bioavailability, accompanied by prolonged systemic circulation.
CONCLUSION: TPGS-enabled micellar encapsulation significantly enhances the oral delivery profile of CAB, offering a promising, noninvasive, and patient-compliant alternative to parenteral antiretroviral regimens, potentially improving therapeutic outcomes in HIV management.