Polymeric Nanostructures as Colloidal Drug Delivery Systems: Thermosensitive Hydrogels Containing Self-Assembled Micelles

Abstract

Polymeric nanostructures for drug delivery applications including smart hydrogels and stealth micelles have been developed to overcome many obstacles in the way of timing and targeting the delivery to fulfill therapeutic potentiality of chemicals. The purpose of this investigation is to prepare and characterize novel nanoparticle-based colloidal products composed of biocompatible polymers to use for rate-controlled release and targeted/spatial drug delivery systems, aiming specifically at drug delivery via mucosal routes. We formulated the new products with inert and biocompatible polymers including sodium carboxymethylcellulose (NaCMC) and polysorbates. The synthesis process was performed by heating/cooling method, as a type of physical cross-linking method for producing hydrogel, in three steps to optimize physical and chemical characteristics of the products to make them suitable for delivery through mucosal routes. A series of nanoparticle-based colloidal products in the form of liquid suspensions were developed, and from all three steps, thirty-nine samples were selected and rheologically investigated by bench-top experiments. A freeze-thawing method was applied to two samples of product III10 for five and one repeated cycles sequentially. Test tube inversion method was also carried out on all the produced gels. Most of the products are new types of temperaturesensitive, smart, physically self-assembled hydrogels and took the forms of sol, gel (opaque and transparent), and precipitate. However, these hydrogels show opposite gelation property to customary temperature-sensitive gels. The product of five repeated freezing-thawing cycles is also thermoreversible gel with a high mechanical stability and swelling capacity, as opposed to the product of one cycle. Some types of produced hydrogels behave like a ternary system. The products of this work, with microstructure consisting of the polymeric chains of sodium carboxymethylcellulose and a large-scale self-assembly of micellar structures of polysorbates incorporated within a polymer network, show major efficacy of site-specific and controlled release drug delivery system.