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MULTIFUNCTIONAL SCAFFOLDS FOR DRUG-DELIVERY THERAPIES

Borges, Thiago FCC
http://rave.ohiolink.edu/etdc/view?acc_num=case1449014240

Abstract Details

2016, Doctor of Philosophy, Case Western Reserve University, Macromolecular Science and Engineering.
Drug delivery systems are responsible for transporting a pharmaceutical agent into a specific part of the body as needed. Besides finding a matrix that releases the drug properly, it is desirable to choose an appropriate process that helps to enhance the therapeutic effect. Electrospinning, a method that draws micro or nanofibers using an electrical charge, provides an opportunity to improve cell attachment, drug loading, and mass transfer properties. Furthermore, the three-dimension of electrospun scaffolds have high porosity similar to the natural extracellular matrix, making them good candidates for tissue engineering and regenerative medicine. Described herein is the work toward combining drug delivery properties with electrospinning to develop multifunctional scaffolds for three different applications. First, electrospun crosslinked poly(acrylic acid) (PAA) fibers were obtained in order to create a hydrogel for chemoembolization procedures. More specifically, electrospun PAA samples were prepared to deliver doxorubicin and irinotecan via ion-exchange. Since both drugs are used in salt form, the gels were first neutralized prior drug loading, which converted the carboxylic form into sodium carboxylate groups. The performance of the gels regarding drug loading and elution profiles of both drugs were compared to two commercial market leaders: Hepasphere™ and DC Bead®. The amount of drugs incorporated was similar to the commercial brands; however, the higher surface area of scaffolds prolonged the release of the drugs. The antiproliferative activity of doxorubicin and irinotecan was successfully assessed in the A375 melanoma and DLD1 adenocarcinoma cell lines. Additionally, induced clotting assays using human plasma showed that the scaffolds also induced thrombus formation, which make them good candidates for chemoembolic device. Secondly, electrospinning were used to develop a drug-eluting biodegradable graft for covered stents. The grafts were prepared using a tri-layered configuration composed of poly(lactic-co-glycolic acid)/polycaprolatone/ poly(lactic-co-glycolic acid) (PLGA/PCL/PLGA). The drug was successfully incorporated in the abluminal PLGA layer and eluted via diffusion. According to the concentration of sirolimus, a range of 95-81% of drug was delivery in an estimated time of 30 days, similar to commercial drug-eluting stents. The PCL layer was melted to provide additional adhesion properties between the graft and the stent platform. Besides acting as an adhesive for the graft, the molten PCL also helped to control the direction of the elution. The elution profile into the abluminal direction showed to be faster than the luminar direction. The probability of a clot formation was tested in ex-vivo experiments using swine blood. The percentage of thrombus formed on the surface of the electrospun graft matched to bare metal platform, demonstrating the safety of the device. Finally, clotrimazole dissolved in oil was successfully incorporated into in-situ crosslinked gelatin scaffolds using emulsion electrospinning. This strategy aims to produce formulation for intra-vaginal device for treatment fungal infections. The final scaffold had a morphology of fibers with oil droplets of drug. The elution profile presented a burst release of approximately 90% of clotrimazole in 20 min, followed by the release of the remained drug in 90 min. The antifungal activity was demonstrated in vitro against Aspergillus fumigatus in samples with dosage of 2.5 and 5.0 mg of clotrimazole per mL of oil. Although no significant difference was observed in the antifungal activity when compared with gelatin gels loaded with the same concentration of clotrimazole, the scaffolds absorbed 4x faster water than gels, which may lead to a faster and stronger mucoadhesion property.
Gary Wnek (Advisor)
Hatsuo Ishida (Committee Member)
Alex Jamieson (Committee Member)
John Pink (Committee Member)
113 p.
Polymers
electrospinning, drug-delivery, doxorubicin, irinotecan, sirolimus and clotrimazole

Recommended Citations

Citations

  • Borges, T. F. (2016). MULTIFUNCTIONAL SCAFFOLDS FOR DRUG-DELIVERY THERAPIES [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1449014240

    APA Style (7th edition)

  • Borges, Thiago. MULTIFUNCTIONAL SCAFFOLDS FOR DRUG-DELIVERY THERAPIES. 2016. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1449014240.

    MLA Style (8th edition)

  • Borges, Thiago. "MULTIFUNCTIONAL SCAFFOLDS FOR DRUG-DELIVERY THERAPIES." Doctoral dissertation, Case Western Reserve University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=case1449014240

    Chicago Manual of Style (17th edition)

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This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.