Tunable Release of Multiclass Anti-HIV Drugs that are Water-Soluble and Loaded at High Drug Content in Polyester Blended Electrospun Fibers
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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.
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.
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.
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.
KEY WORDSelectrospinning high loading HIV programmable release tenofovir
Percent change in water content
Polymer mass loss percentage
T cell line
Total amount of drug loss
Dulbecco’s Modified Eagle’s Medium
Dulbecco’s phosphate buffered saline
Differential scanning calorimetry
Fetal bovine serum
High performance liquid chromatography
Half maximal inhibition concentration
Power law slope parameter
Sample mass after drying
Sample mass prior to analysis
Amount of drug release at time (t)
Amount of total drug release from the sample
Wet sample mass
Power law expression, release mechanism
T cell line
Relative luminescence unit
Scanning electron microscopy
Active metabolite of irinotecan
Median tissue culture infective does
Tenofovir disoproxil fumarate
Glass transition temperature
HeLa cell line
ACKNOWLEDGMENTS AND DISCLOSURE
The authors thank the UW-NNIN for assistance with SEM imaging, and T. Kuykendall (UW MSE) for assistance with DSC. Raltegravir and maraviroc samples were purified from their pharmaceutical formulations by M. Ebner, A. Bever and I. Suydam (Seattle University). This work was supported by grants to K.A.W. from the Bill and Melinda Gates Foundation (OPP11110945) and the National Institutes of Health (AI098648, AI112002).
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