Modulation of the encapsulation and release of the antiretroviral efavirenz by n-alkylation of poloxamine polymeric micelles

CHIAPPETTA D.A.; ALVAREZ-LORENZO C.; TABOADA P.; CONCHEIRO A.; SOSNIK A.

Kottayam

Congreso; First World Conference on Nanomedicine and Drug Delivery (WCN 2010); 2010

Institute of Macromolecular Science and Engineering (IMSE) and Institute for Holistic Medical Sciences (IHMS)

Encapsulation of poorly water-soluble drugs within the hydrophobic core of polymeric micelles represents one of the most attractive nanotechnological strategies to improve their aqueous solubility. Poloxamine block copolymers possess a X-shaped structure that consists of an ethylenediamine central group bonded to four chains of poly(propylene oxide)-poly(ethylene oxide) (PPO-PEO) blocks. Such a particular structure makes poloxamines sensitive to both temperature and pH and, consequently, their self-aggregation status depends on the physiological values of these variables. Furthermore, the presence of reactive groups in the core can be capitalized to produce positively charged copolymers (e.g., N-methylated derivatives) in order to modulate core-drug interactions. Thus, compared to their linear counterpart poloxamers, poloxamines may behave as more versatile drug nanocarriers. This work investigated the self-associative behavior of a variety of N-methylated poloxamines and compared pristine and N-methylated poloxamines regarding the encapsulation and in vitro delivery of efavirenz (EFV), a first-line antiretroviral used in the pharmacotherapy of HIV. Findings indicated that poloxamines and their N-methylated derivatives render micelles capable of hosting high amounts of EFV, remarkably increasing its apparent aqueous solubility. The EO/PO ratio of poloxamine determines the solubilization capability, while N-methylation provides the copolymer with the ability to fasten the release of the drug under physiological conditions. These findings point out poloxamines and N-methylated poloxamines as highly versatile nanocarriers for oral or parenteral delivery of once-a-day dose of EFV.