Robust strategies to reduce burst and achieve tunable control over extended drug release from uniaxially electrospun composites

Joy, Nikhita and Venugopal, Dhivya and Samavedi, Satyavrata (2022) Robust strategies to reduce burst and achieve tunable control over extended drug release from uniaxially electrospun composites. European Polymer Journal, 168. pp. 1-11. ISSN 0014_3057

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In this study, robust strategies were developed to prepare uniaxially electrospun composites that reduced initial burst and provided controlled release of budesonide (a clinically important corticosteroid) over an extended timeframe in vitro. First, poly(caprolactone) (PCL) meshes were shown to exhibit significant burst while poly(D,L-lactide-co-glycolide) 85:15 (PLGA) meshes intrinsically promoted zero-order release over 28d. In-depth characterization of the architectural, physico-chemical and thermal properties revealed differences in gross morphological behavior, water uptake capacity, polymer Tg, and drug affinity to the matrix as factors governing release. Based on this mechanistic understanding of release from fast- and slow-releasing polymers, PCL and PLGA were next judiciously blended in a specific ratio i.e., 20PCL/80PLGA to achieve controlled first-order release over 28d at a faster rate than PLGA but without an initial burst. Interestingly, increasing the PCL content to 30% (i.e., a 30PCL/70PLGA blend) resulted in a sharp burst release. Since the release from the 30PCL/70PLGA blend depended on intrinsic system characteristics, a dual-spinneret co-electrospinning approach was employed to effectively decouple fiber properties and achieve precise drug distribution across independently integrated PCL and PLGA fibers. Consequently, the co-electrospun meshes — possessing identical polymer compositions and drug/polymer ratios as the 30PCL/70PLGA blend — exhibited no burst and resulted in predictable release characterized by 10d zero-order kinetics. Notably, neither the rationally guided blending nor the co-electrospinning strategy involved the use of cytotoxic cross-linkers, bioactivity-reducing excipients, delamination-prone barrier layers and complex set-ups. Based on the application, a rational choice of blend ratios or co-electrospinning parameters may be used to tune the rate of release from the composites. © 2022 Elsevier Ltd

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IITH Creators:
IITH CreatorsORCiD
Samavedi, SatyavrataUNSPECIFIED
Item Type: Article
Additional Information: This work was supported by the Science and Engineering Research Board, Department of Science and Technology, India (grant number ECR/2016/000132). Micrographs were obtained with the help of a SEM procured through a grant (grant number SR/FST/ETI-421/2016) to the Indian Institute of Technology Hyderabad. The authors are thankful to Vrushank K (IIT Hyderabad) for assistance with conducting some of the release studies reported in this manuscript.
Uncontrolled Keywords: Blended composites; Co-electrospinning; Electrospun fibers; Polymer miscibility; Predictable drug release; Simultaneous electrospinning; Tunable zero-order drug release
Subjects: Chemical Engineering
Divisions: Department of Chemical Engineering
Depositing User: . LibTrainee 2021
Date Deposited: 02 Jul 2022 09:47
Last Modified: 13 Jul 2022 10:42
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