Hyaluronic acid incorporation modulates rheological and drug release properties in Poloxamer-based hydrogels

Abstract

INTRODUCTION: Synthetic polymer Poloxamer (PL) 407 (15% and 30% w/w) and binary formulation PL 407 15% + PL 338 15% (BF), with natural polymer hyaluronic acid 0.5% w/w, were designed as bupivacaine or ropivacaine thermosensitive release systems. OBJECTIVES: The aim of this work is to characterize structure and stability of drug delivery systems. MATERIALS AND METHODS: These systems were characterized by calorimetry, rheology, SANS, and release profile. DISCUSSION AND RESULTS: Calorimetry results demonstrated all formulations are stable at storage and physiological temperatures. PL 407 30% and BF systems are structurally more organized and with higher consistency (G’/G’’ ~ 50) at 37 °C and with lower gelation temperature (Tg ~ 14 °C) than PL 407 15% ones (G’/G’’ ~ 0.30 and Tg ~ 45 °C, respectively), however BFs have increased viscosity and slightly higher stiffness (G’/G’’ ~ 60) when compared to PL 407 30% formulations, due to more hydrophilicity of PL 338 chains than PL 407. Adding HA, it is observed enhanced viscosity but diminished consistency (G’/G’’ ~ 0.40). When a drug is incorporated, it is seen that it promotes increased interaction between chains. Although material alteration when incorporating HA or drug is observed, SANS results showed that the type of supramolecular structure is dependent on the concentration of Poloxamer. Systems with low concentration of Poloxamer have lamellar type, while formulations with 30% of Poloxamer have both cubic and hexagonal structures. In addition, PL 407 30% formulations undergo greater compression when bupivacaine is added (~ 29.7 nm at 25 °C and 37 °C). As drug release profiles showed, BFs release drugs in a more controlled way than other formulations. Moreover, HA hinders the release of both drugs. CONCLUSION: Thus, it is clear that the incorporation of more hydrophilic polymers is able to modulate the drug release rate according to the hydrogels rheological parameters.