(180u) Evaluation of Cellulose Ethers for Design of Polymeric Delivery Vehicles

Cellulose ethers are widely produced polymers with an array of chemical and biomedical applications. Understanding the physical properties of these polymers is crucial in the selection of the proper cellulose ether solutions for a specific application. Our method of evaluation and design begins with the collection of rheological data on cellulose ether solutions, followed by correlation of these experimental data to the structures of the cellulose ethers, and then the use of these correlations to rationally design cellulose ether solutions that match a specific set of target physical properties. The design of these polymer solutions thus entails optimizing the molecular structure of the polymer to specific target property requirements. Computational Molecular Design (CMD) provides the methodology for this design problem. In this approach, Quantitative Structure-Property Relationships (QSPRs) are generated and validated to relate the structure of the polymers to their rheological properties.

In this study, five hydroxyethyl cellulose and three carboxymethyl cellulose polymers were hydrated at different concentrations, resulting in a total of 29 polymer solutions. The rheological properties of these 29 cellulose ether solutions were measured. These measurements included the viscosity, fit to a power-law model and reported as consistency and shear-thinning index, and the elastic properties, reported as storage modulus and loss modulus. These data were analyzed to reveal trends in the variation of rheological properties due to changes in solution concentration, polymer average molecular weight, and degree of polymer side chain substitution. Concurrently, molecular topological indices, in this case connectivity indices, were generated as a quantitative method to represent the polymer structure. QSPRs were then generated by regressing these topological indices, with the additional structural parameters of average molecular weight and polymer concentration, to generate an equation for each relevant rheological property. These QSPRs are widely applicable to the design of cellulose ether solutions for a variety of applications.

One such design use is the formation of polymeric delivery vehicles. Novel therapeutics are required to prevent the transmission of HIV/AIDS to women in developing countries. These therapeutics must also be easily produced and distributed and also affordable. HIV/AIDS is a leading cause of death in developing countries and affects female populations disproportionately. In some countries, women account for over 60% of the total infection rate. Current preventative measures are not adequately combating this pandemic, and thus new preventative measures are needed. One approach is vaginal microbicides, which combine an active drug agent with a delivery vehicle. This delivery vehicle can be a gel, cream, or polymeric solution. There is a research need to develop more effective delivery vehicles with target properties that will provide optimal epithelial-coating behavior and serve as a barrier to infection. These target properties were obtained from concurrent in vitro and in vivo experiments as well as a review of relevant literature. The above QSPRs, along with target rheological properties that correspond to optimal spreading behavior, were incorporated into an optimization model, which when solved provides candidate novel cellulose ether solutions with physical properties near the ideal values. These QSPRs are also useful for the design of cellulose ethers in many other chemical and biomedical applications.