Instytut Podstawowych Problemów Techniki

UMO-2019/35/N/ST5/03882

2020-07-09 / 2024-05-08

Jedyny wykonawca

NCN

PRELUDIUM

18

The main objective of this project is to systematically investigate physicochemical properties of a multicomponent nanofibrous polymer drug delivery system (DDS) containing brinzolamide, an ophthalmic active ingredient. Nanofibers will be formed by hydroxypropyl cellulose and polycaprolactone in various ratios, serving as a matrix for brinzolamide, which will be dispersed in it in form of inclusion complex with β- cyclodextrin. Combination of hydrophilic and hydrophobic ingredients will allow for a gradual biodegradation of the nanofibers and a sustained drug release. Thanks to hydroxypropyl cellulose presence, they will also possess mucoadhesive properties. The perspective goal is the development of a multicomponent nanofibrous polymer DDS containing brinzolamide for the innovative treatment of glaucoma. Nanofibers will be formed via an electrospinning technique. Electrospun nanofibers are well known for allowing sustained and controlled delivery of many active ingredients, yet so far their potential in ophthalmic applications has not been sufficiently used. Cyclodextrins in water formulations have been however proven to improve water solubility of brinzolamide, enabling to create its reservoir in the destination place and increasing its permeability to target tissues. It is assumed here that incorporating cyclodextrin-drug complexes into nanofibers will allow to fully use their potential – because of the more local application, due to strong attachment of nanofibers to mucins, and a more controlled and more effective drug delivery to the destination place. Moreover, as complexation enhances drug stability, the proposed DDS will eliminate the need to add pH modifiers and preservatives, both giving traditional ophthalmic formulations an irritant character. The project application is supported by successful results of the preliminary studies. Hexafluoroisopropanol (HFiP) was selected as a solvent for system, which was supported by demonstrating BRZ resistance to it. The complexation efficiency in HFiP was proven – binding stoichiometry of the complex was determined in a complex formation study using UV-Vis spectroscopy and stability constant was calculated. Franz diffusion cell with a spherical joint for corneal work was made to order for permeation tests. Mucoadhesion study with micromechanical tester was initiated with a special holder made in cooperation with the Department of Mechanics of Materials. A number of tests will be carried out in order to achieve the objectives of the project. Impact of different chemical composition on physicochemical properties of the materials will be evaluated. The concentration and weight ratios of components in nanofibers will be tuned throughout the study to provide an appropriate drug content, longest possible time of stable drug release and mucoadhesive properties allowing the system to stay in place for such time. In detail, in the frame of the project it is proposed to investigate microstructure, thermal properties, mucoadhesion, interaction between drug complexes and a polymer matrix and cytotoxicity of the materials, as well as drug permeability kinetics through porcine cornea and synthetic membrane. All these activities will provide a valuable information in terms of basic research and in the field of drug delivery systems. The impact of the project results on the development of the research field and scientific discipline will be significant. Combination of hydroxypropyl cellulose with polycaprolactone and cyclodextrin-drug complexes will lead to obtain a multi-component material of a unique structure and of an exceptional release profile of the active ingredient. Potential application area of the material is ophthalmic. Ophthalmic drugs carriers bring many benefits, including increase of the therapy effectiveness and biodegradability. In the future, this project may lead to the design of an innovative mucoadhesive material supporting the treatment of an open angle glaucoma.