Efavirenz-Loaded Polymeric Micelles for Pediatric Anti-HIV Pharmacotherapy with Significantly Higher Oral Bioavailability

Abstract

Children constitute the most challenging population in anti-HIV/AIDS pharmacotherapy. Efavirenz (EFV; aqueous solubility 4 µg/ml, bioavailability 40–45%) is a first-line agent in the pediatric therapeutic cocktail. The liquid formulation of EFV is not available worldwide, preventing appropriate dose adjustment and more convenient administration. The bioavailability of liquid EFV is lower than that of the solid formulation. Improving the bioavailability of the drug would reduce the cost of treatment and enable less affluent patients to access this drug. Aim: To encapsulate EFV in polymeric micelles to improve the aqueous solubility and the the oral bioavailability of the drug. Methods: EFV was incorporated into the core of linear and branched poly(ethylene oxide)–poly(propylene oxide) block copolymer micelles. The size and size distribution of the drug-loaded aggregates were characterized by dynamic light scattering and the morphology by transmission electron microscopy. The bioavailability of the EFV-loaded micellar system (20 mg/ml) was assessed in male Wistar rats (40 mg/kg) and compared to that of a suspension prepared with the content of EFV capsules in 1.5% carboxymethylcellulose PBS solution (pH 5.0), and an EFV solution in a medium-chain triglyceride (Miglyol^® 812). Results: This work demonstrates that the encapsulation of EFV, which is poorly water soluble, into polymeric micelles of different poly(ethylene oxide)–poly(propylene oxide) block copolymers significantly improves the oral bioavailability of the drug, and reduces the interindividual variability. Conclusion: This strategy appears a very promising one towards the development of a liquid aqueous EFV formulation for the improved pediatric HIV pharmacotherapy.

Keywords::

• bioavailability
• efavirenz solubilization
• improved solubility
• interindividual variability
• pediatric HIV/AIDS pharmacotherapy
• poloxamer and poloxamine polymeric micelles

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Corrigendum

Corrigendum

Financial & competing interests disclosure

The authors thank the University of Buenos Aires for financial support (Grant UBACyT-0064). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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Funding

The authors thank the University of Buenos Aires for financial support (Grant UBACyT-0064). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.