Poornima Ramburrun1, Pradeep Kumar1, Yahya E Choonara1, Lisa C du Toit1, Viness Pillay1. 1. a Wits Advanced Drug Delivery Platform Research Unit, Department of Pharmacy and Pharmacology, School of Therapeutic Sciences, Faculty of Health Sciences , University of the Witwatersrand , Johannesburg , South Africa.
Abstract
OBJECTIVES: The purpose of this study was to develop novel, porous neurodurable interpenetrating networks of gellan-xanthan hydrogel conduits intercalated with pristine polymethyl methacrylate (PMMA) particles for the sustained and concurrent release of two model compounds: bovine serum albumin (BSA) and diclofenac sodium. METHODS: Hydrogel conduits were synthesized using a thermal-ionic crosslinking mechanism with direct incorporation of PMMA. The 15 formulations, generated using a Box-Behnken experimental design, were analyzed for drug release, swelling, erosion and textural properties. RESULTS: The 15 formulations provided a near zero-order release of BSA (37-75% fractional release) and diclofenac sodium (14-22% fractional release) over 20 and 30 days, respectively, modulated via a combination of pH-responsive (pH 7.4) dissolution of the intercalated pristine polymer particles and the unique gelling and erosion properties imparted by the graded addition of xanthan gum to the hydrogel blend. The concentration-dependent intercalation of PMMA extended drug release rates and enhanced matrix resilience from 31% to 56%. CONCLUSIONS: The gellan-xanthan ratio variability and the pore-inducing effects of intercalated PMMA yielded a means for fine tuning the mechanical attributes of the hydrogel matrices, particularly matrix rigidity and flexibility, offering an appealing strategy for the design and development of synthetic bioactive-releasing peripheral nerve repair conduits.
OBJECTIVES: The purpose of this study was to develop novel, porous neurodurable interpenetrating networks of gellan-xanthan hydrogel conduits intercalated with pristine polymethyl methacrylate (PMMA) particles for the sustained and concurrent release of two model compounds: bovine serum albumin (BSA) and diclofenac sodium. METHODS: Hydrogel conduits were synthesized using a thermal-ionic crosslinking mechanism with direct incorporation of PMMA. The 15 formulations, generated using a Box-Behnken experimental design, were analyzed for drug release, swelling, erosion and textural properties. RESULTS: The 15 formulations provided a near zero-order release of BSA (37-75% fractional release) and diclofenac sodium (14-22% fractional release) over 20 and 30 days, respectively, modulated via a combination of pH-responsive (pH 7.4) dissolution of the intercalated pristine polymer particles and the unique gelling and erosion properties imparted by the graded addition of xanthan gum to the hydrogel blend. The concentration-dependent intercalation of PMMA extended drug release rates and enhanced matrix resilience from 31% to 56%. CONCLUSIONS: The gellan-xanthan ratio variability and the pore-inducing effects of intercalated PMMA yielded a means for fine tuning the mechanical attributes of the hydrogel matrices, particularly matrix rigidity and flexibility, offering an appealing strategy for the design and development of synthetic bioactive-releasing peripheral nerve repair conduits.