title: Electrospun Polymer Blend Nanofibers for Tunable Drug Delivery: The Role of Transformative Phase Separation on Controlling the Release Rate.
abstract: Electrospun fibrous materials have a wide range of biomedical applications, many of them involving the use of polymers as matrices for incorporation of therapeutic agents. The use of polymer blends improves the tuneability of the physicochemical and mechanical properties of the drug loaded fibers. This also benefits the development of controlled drug release formulations, for which the release rate can be modified by altering the ratio of the polymers in the blend. However, to realize these benefits, a clear understanding of the phase behavior of the processed polymer blend is essential. This study reports an in depth investigation of the impact of the electrospinning process on the phase separation of a model partially miscible polymer blend, PVP K90 and HPMCAS, in comparison to other conventional solvent evaporation based processes including film casting and spin coating. The nanoscale stretching and ultrafast solvent removal of electrospinning lead to an enhanced apparent miscibility between the polymers, with the same blends showing micronscale phase separation when processed using film casting and spin coating. Nanoscale phase separation in electrospun blend fibers was confirmed in the dry state. Rapid, layered, macroscale phase separation of the two polymers occurred during the wetting of the fibers. This led to a biphasic drug release profile from the fibers, with a burst release from PVP-rich phases and a slower, more continuous release from HPMCAS-rich phases. It was noted that the model drug, paracetamol, had more favorable partitioning into the PVP-rich phase, which is likely to be a result of greater hydrogen bonding between PVP and paracetamol. This led to higher drug contents in the PVP-rich phases than the HPMCAS-rich phases. By alternating the proportions of the PVP and HPMCAS, the drug release rate can be modulated.
authors.affiliation: School of Pharmacy, University of East Anglia , Norwich, Norfolk NR4 7TJ, U.K.
authors.forename: Pratchaya
authors.initials: P
authors.lastname: Tipduangta
authors.affiliation: School of Chemistry, University of East Anglia , Norwich, Norfolk NR4 7TJ, U.K.
authors.forename: Peter
authors.initials: P
authors.lastname: Belton
authors.affiliation: School of Pharmacy, University of East Anglia , Norwich, Norfolk NR4 7TJ, U.K.
authors.forename: László
authors.initials: L
authors.lastname: Fábián
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, China.
authors.forename: Li Ying
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Centre for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences , Wuhan 430071, China.|State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, Metabonomics and Systems Biology Laboratory, School of Life Sciences, Fudan University , Shanghai 200433, China.
authors.forename: Huiru
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Chemistry, University of Cambridge , Cambridge CB2 1TN, U.K.
authors.forename: Mark
authors.initials: M
authors.lastname: Eddleston
authors.affiliation: School of Pharmacy, University of East Anglia , Norwich, Norfolk NR4 7TJ, U.K.
authors.forename: Sheng
authors.initials: S
authors.lastname: Qi
mesh_terms: D003692:Delayed-Action Preparations / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D057139:Nanofibers / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers
keywords: electrospinning; phase separation; polymer blends; tunable drug release