No abstract

Ultrafiltration (UF) and microfiltration (MF) membranes have important applications in separations related to proteins, pharmaceutical products, viruses, food and beverages, water treatment, and sterilization. Although phase inversion membranes have been used for MF and UF applications for decades, there has been, instead, an increase in interest in using electrospun fibrous mats as MF/UF membranes. Although the selectivity–permeability tradeoff for conventional phase-inversion UF membranes is now established, such an understanding for phase-inversion MF membranes and for fibrous mat membranes does not exist. Here, we report the first preliminary selectivity–permeability tradeoff for commercially available MF membranes. We also describe a theoretical framework that can be used to evaluate the performance of fibrous mats. Mats consisting of a random array of nanofibers were modeled with a gamma pore size distribution, based on previous work. The pore size distribution of the mat was related to the physical properties of the mat, such as porosity, fiber diameter, density, areal density, and mat thickness. This distribution was then used in conjunction with a procedure developed by Zydney and co-workers to conduct a priori predictions of the performance of fibrous mats, UF, and MF membranes in terms of their hydraulic permeability and selectivity to the model solutes, 3.65 nm radius bovine serum albumin (BSA) and 100 nm radius microspheres, respectively. We compared the performance of modeled mats of varying properties with the selectivity–permeability trade-off curve of current UF and MF membranes. A surprising finding was that, as modeled, the performance of fibrous mat membranes can only surpass that of current UF and MF membranes under very limited conditions. These conditions include very low fiber diameters of ∼2 nm and ∼70 nm and membrane thicknesses of <100 nm and <1000 nm for UF and MF membranes, respectively. These metrics are challenging to achieve under currently used manufacturing conditions.

Sustained drug delivery strategies have many potential benefits for treating a range of diseases, particularly chronic diseases that require treatment for years. For many chronic ocular diseases, patient adherence to eye drop dosing regimens and the need for frequent intraocular injections are significant barriers to effective disease management. Here, we utilize peptide engineering to impart melanin binding properties to peptide-drug conjugates to act as a sustained-release depot in the eye. We develop a super learning-based methodology to engineer multifunctional peptides that efficiently enter cells, bind to melanin, and have low cytotoxicity. When the lead multifunctional peptide (HR97) is conjugated to brimonidine, an intraocular pressure lowering drug that is prescribed for three times per day topical dosing, intraocular pressure reduction is observed for up to 18 days after a single intracameral injection in rabbits. Further, the cumulative intraocular pressure lowering effect increases ~17-fold compared to free brimonidine injection. Engineered multifunctional peptide-drug conjugates are a promising approach for providing sustained therapeutic delivery in the eye and beyond.