Liquid crystalline structure affects drug release from Pluronic® gels

Pluronic® gels loaded with Bupivacaine salt of linolenic acid (Bup-γL) were successfully developed in the past for oral mucositis pain control. The mechanisms of drug release from such Pluronic® gels have not yet been fully understood. The objective of this study was to explore the underlying mechanisms of drug release from Pluronic® gels with or without interference by sodium lauryl sulfate (SLS). The in vitro release of the hydrophilic bupivacaine salt (bupivacaine hydrochloride, BupHCl) as well as two hydrophobic bupivacaine salts (bupivacaine salt of linolenic acid, Bup-γL; and bupivacaine salt of linoleic acid, Bup-L) formulated in Pluronic® gels was performed. The liquid crystalline structure, the rheological properties and the thermal properties of these Pluronic® formulations were analyzed using small-angle X-ray scattering (SAXS), rheology and nano differential scanning calorimetry (nano DSC), respectively. The release of hydrophobic Bup-γL and Bup-L was significantly slowed down in SLS induced body-centered cubic (bcc) and face-centered cubic (fcc) structures in the Pluronic® gels, compared with the hexagonal structure in the Pluronic® gels without SLS. On the other hand, the release of BupHCl from the Pluronic® gels was not significantly different in the SLS induced lamellar structure and in the hexagonal structure (without SLS). In brief, the liquid crystalline structure in the Pluronic® gels did not influence the release of the hydrophilic drug yet significantly affected the release of the hydrophobic drugs. This is the first report revealing the release mechanisms of bupivacaine salts from Pluronic® gels through exploring their liquid crystalline structures. The findings not only provide an in-depth understanding of the drug release from the Pluronic® gels developed previously for oral mucositis pain control, but more importantly, offer valuable insight to assist future Pluronic® based formulation design for drug release control.