Tunable Release of Multiclass Anti-HIV Drugs that are Water-Soluble and Loaded at High Drug Content in Polyester Blended Electrospun Fibers.

OBJECTIVES: Sustained release of small molecule hydrophilic drugs at high doses remains difficult to achieve from electrospun fibers and limits their use in clinical applications. Here we investigate tunable release of several water-soluble anti-HIV drugs from electrospun fibers fabricated with blends of two biodegradable polyesters. METHODS: Drug-loaded fibers were fabricated by electrospinning ratios of PCL and PLGA. Fiber morphology was imaged by SEM, and DSC was used to measure thermal properties. HPLC was used to measure drug loading and release from fibers. Cytotoxicity and antiviral activity of drug-loaded fibers were measured in an in vitro cell culture assay. RESULTS: We show programmable release of hydrophilic antiretroviral drugs loaded up to 40 wt%. Incremental tuning of highly-loaded drug fibers within 24 h or >30 days was achieved by controlling the ratio of PCL and PLGA. Fiber compositions containing higher PCL content yielded greater burst release whereas fibers with higher PLGA content resulted in greater sustained release kinetics. We also demonstrated that our drug-loaded fibers are safe and can sustain inhibition of HIV in vitro. CONCLUSIONS: These data suggest that we were able to overcome current limitations associated with sustained release of small molecule hydrophilic drugs at clinically relevant doses. We expect that our system represents an effective strategy to sustain delivery of water-soluble molecules that will benefit a variety of biomedical applications.

Current strategies for sustaining drug release from electrospun nanofibers.

Electrospun drug-eluting fibers are emerging as a novel dosage form for multipurpose prevention against sexually transmitted infections, including HIV, and unintended pregnancy. Previous work from our lab and others show the versatility of this platform to deliver large doses of physico-chemically diverse agents. However, there is still an unmet need to develop practical fiber formulations for water-soluble small molecule drugs needed at high dosing due to intrinsic low potency or desire for sustained prevention. To date, most sustained release fibers have been restricted to the delivery of biologics or hydrophobic small molecules at low drug loading of typically <1 wt.%, which is often impractical for most clinical applications. For hydrophilic small molecule drugs, their high aqueous solubility and poor partitioning and incompatibility with insoluble polymers make long-term release even more challenging. Here we investigate several existing strategies to sustain release of hydrophilic small molecule drugs that are highly-loaded in electrospun fibers. In particular, we investigate what is known about the design constraints required to realize multi-day release from fibers fabricated from uniaxial and coaxial electrospinning.

Multilayered, Hyaluronic Acid-Based Hydrogel Formulations Suitable for Automated 3D High Throughput Drug Screening of Cancer-Stromal Cell Cocultures.

Validation of a high-throughput compatible 3D hyaluronic acid hydrogel coculture of cancer cells with stromal cells. The multilayered hyaluronic acid hydrogels improve drug screening predictability as evaluated with a panel of clinically relevant chemotherapeutics in both prostate and endometrial cancer cell lines compared to 2D culture.

Optical performance of hydrophobic acrylic intraocular lenses with surface light scattering.

PURPOSE: To evaluate the potential effect of surface light scattering on the optical performance of hydrophobic acrylic intraocular lenses (IOLs) made of Acrysof material. SETTING: Alcon Laboratories, Inc., Fort Worth, Texas, USA. DESIGN: Experimental study. METHODS: Explanted IOLs from cadaver eyes with more than 50 computer-compatible tape (CCT) units of scatter were selected, yielding 7 IOLs. Clinically explanted IOLs (n = 4) were obtained after IOLs had been implanted 8.5 to 10.5 years. Explanted IOLs were matched to unused control IOLs. After proteins were removed, scatter was measured for IOLs dry, wetted (2 minutes in a balanced salt solution), and hydrated (24 hours). Badal imaging, ultraviolet-visible transmission, and modulation transfer function (MTF) measurements were performed with hydrated IOLs. RESULTS: Hydrated scatter values ranged from 80 to 221 CCT for explanted IOLs and 2 to 7 CCT for controls. No differences in Badal image resolution were observed between explanted IOLs and controls. The mean MTF values at 100 line pairs per mm (representing 20/20 visual acuity) were similar between explanted IOLs and controls. Over the range of 400 to 700 nm, a small reduction (mean 2.1% ± 1.4% [SD]) in transmission was observed. CONCLUSIONS: Surface light scattering of explanted IOLs did not affect image resolution or MTF values. Although light transmission was slightly decreased, the magnitude appeared to be inconsequential for optical performance.

Capillary force lithography for cardiac tissue engineering.

Cardiovascular disease remains the leading cause of death worldwide(1). Cardiac tissue engineering holds much promise to deliver groundbreaking medical discoveries with the aims of developing functional tissues for cardiac regeneration as well as in vitro screening assays. However, the ability to create high-fidelity models of heart tissue has proven difficult. The heart's extracellular matrix (ECM) is a complex structure consisting of both biochemical and biomechanical signals ranging from the micro- to the nanometer scale(2). Local mechanical loading conditions and cell-ECM interactions have recently been recognized as vital components in cardiac tissue engineering(3-5). A large portion of the cardiac ECM is composed of aligned collagen fibers with nano-scale diameters that significantly influences tissue architecture and electromechanical coupling(2). Unfortunately, few methods have been able to mimic the organization of ECM fibers down to the nanometer scale. Recent advancements in nanofabrication techniques, however, have enabled the design and fabrication of scalable scaffolds that mimic the in vivo structural and substrate stiffness cues of the ECM in the heart(6-9). Here we present the development of two reproducible, cost-effective, and scalable nanopatterning processes for the functional alignment of cardiac cells using the biocompatible polymer poly(lactide-co-glycolide) (PLGA)(8) and a polyurethane (PU) based polymer. These anisotropically nanofabricated substrata (ANFS) mimic the underlying ECM of well-organized, aligned tissues and can be used to investigate the role of nanotopography on cell morphology and function(10-14). Using a nanopatterned (NP) silicon master as a template, a polyurethane acrylate (PUA) mold is fabricated. This PUA mold is then used to pattern the PU or PLGA hydrogel via UV-assisted or solvent-mediated capillary force lithography (CFL), respectively(15,16). Briefly, PU or PLGA pre-polymer is drop dispensed onto a glass coverslip and the PUA mold is placed on top. For UV-assisted CFL, the PU is then exposed to UV radiation (λ = 250-400 nm) for curing. For solvent-mediated CFL, the PLGA is embossed using heat (120 °C) and pressure (100 kPa). After curing, the PUA mold is peeled off, leaving behind an ANFS for cell culture. Primary cells, such as neonatal rat ventricular myocytes, as well as human pluripotent stem cell-derived cardiomyocytes, can be maintained on the ANFS(2).