Doubly amphiphilic poly(2-oxazoline)s as high-capacity delivery systems for hydrophobic drugs

Abstract

Solubilization of highly hydrophobic drugs with carriers that are non-toxic, non-immunogenic and well-defined remains a major obstacle in pharmaceutical sciences. Well defined amphiphilic di- and triblock copolymers based on poly(2-oxazolines) were prepared and used for the solubilization of Paclitaxel (PTX) and other water-insoluble drugs. Probing the polymer micelles in water with the fluorescence probe pyrene, an unusual high polar microenvironment of the probe was observed. This coincides with an extraordinary large loading capacity for PTX of 45 wt.% active drug in the formulation as well as high water solubility of the resulting formulation. Physicochemical properties of the formulations, ease of preparation and stability upon lyophilization, low toxicity and immunogenicity suggest that poly(2-oxazoline)s are promising candidates for the delivery of highly challenging drugs. Furthermore, we demonstrate that PTX is fully active and provides superior tumor inhibition as compared to the commercial micellar formulation.

Design Strategies for Functionalized Poly(2-oxazoline)s and Derived Materials

“…Two glass-transistions were detected, indicative of the immiscibility of the two types of blocks in the amphiphilic copoly(2-oxazoline). Kabanov et al synthesized amphiphilic di-and triblock copolymers of the compositions pEtOx-block-p n BuOx and pMeOx-block-p n BuOx-block-pMeOx [179]. These block copolymers formed micelles in water and were used to solubilize otherwise water-insoluble drugs like Paclitaxel.…”

Evaluation of Poly(2-Ethyl-2-Oxazoline) Containing Copolymer Networks of Varied Composition as Sustained Metoprolol Tartrate Delivery Systems

“…However, the use of poly(2-alkyl-2-oxazolines) in drug delivery so far is not well covered, and the research is focused mainly on the systems which increase the solubility of hydrophobic drugs. Luxenhofer et al reported for the synthesis of di-and tri-block copolymers based on poly(2-oxazolines) for the solubilization of water-insoluble drugs (24). Han Y. et al used amphiphilic poly(2-oxazoline)s micelles as a promising high-capacity delivery platform carrying synergistic combinations of multiple chemotherapeutic agents for multidrug cancer chemotherapy.…”

Development and characterization of pioglitazone loaded liposphere for the effective treatment of diabetes mellitus type 2

“…The aim of the present study was to assess the feasibility of formulating lipospheres of Pioglitazone HCl by melt dispersion technique and obtaining a suitable release pattern. [1][2][3][4][5] cetyl alcohol, gelatin were purchased from S.D. Fine Chemicals Ltd. (India).…”