Delivery of Thermoresponsive-Tailored Mixed Micellar Nanogel of Lidocaine and Prilocaine with Improved Dermatokinetic Profile and Therapeutic Efficacy in Topical Anaesthesia

Abstract

The topical delivery of local anaesthetics has always been a difficult task due to the limited percutaneous absorption of local anaesthetic drugs across the various barriers of the skin. In this pursuit, a thermoresponsive mixed micellar nanogel (MMNG) system of lidocaine and prilocaine has been attempted in the current piece of work. The system relies on the ability to alter its phase state (sol-to-gel) for feasibility of the topical application in response to change in temperature. The composition of MMNG entails majorly of Pluronic® F127 and Tween 80 in a fixed combination so as to provide the desired thermoreversibility for the skin application. The gels were optimized with respect to phase transition temperature (T ), turbidity and viscosity. The optimized systems were then characterized for particle size, spreadability, syringeability, bioadhesive strength, ex vivo skin permeation, retention and dermatokinetic studies. The skin compatibility revealed that no histological changes were observed for optimized formulation, while the conventional system showed changes in the skin-tissues. Further, the enhanced intensity of anaesthetic effect was noted in an in vivo rabbit model and tail flick model in mice. The overall results suggest that the prepared MMNG system possesses the potential in providing an efficacious, safe and acceptable alternative therapeutic system for topical anaesthesia.

Hybrid nanofilms as topical anesthetics for pain-free procedures in dentistry

“…The permeation parameters of LDC-PLC from the different films across oral mucosa are displayed in Table 2. LDC and PLC fluxes and apparent permeability coefficient (P aap ) were almost twice higher in hybrid nanofilm in comparison with biopolymer control film, as already described [40][41][42] . In general, PLC flux and P aap were slower than LDC in all samples, as previously reported in gels 3 .…”

A novel local anesthetic system: transcriptional transactivator peptide-decorated nanocarriers for skin delivery of ropivacaine

“…Drug delivery of LAs via the skin brings a lot of benefits such as delivering the local drug continuously and reducing systemic adverse reactions 11,12. Polymeric nanoparticles have been used for skin delivery 13.…”

Thermoresponsive Nanogels Based on Different Polymeric Moieties for Biomedical Applications

“…Different hydrophobic materials are used to conjugate on hydrophilic units to form thermosensitive materials. Many studies have been performed based on this approach, and different hydrophobic materials, such as cholesterol [ 184 , 185 ], poly L-lactide (PLLA) [ 186 , 187 , 188 , 189 ], beta glycerophosphate (β-GP) [ 190 , 191 ] and pluronic F127 (F127) [ 192 , 193 ] have been used to synthesize thermosensitive hydrogels and nanogels for biomedical applications.…”

“…Pluronic F127 is a hydrophilic non-ionic copolymer, based on non-toxic FDA-approved PEG and polypropylene glycol (PPG) segments, which is widely used in biomedical applications [ 192 , 199 , 200 , 201 , 202 , 203 ]. Sharma et al developed a thermosensitive nanogel based on pluronic F127 as the carrier for the delivery of lidocaine (Lid) and prilocaine (Pl) and demonstrated by in-vitro and in-vivo experiments that the thermosensitivity of the carrier improves the delivery of Lid and PI [ 193 ]. Choi et al prepared a nano-sponge based on heparin (Hep) and pluronic F127 and used it as a thermosensitive carrier for the controlled release of growth factors (bFGF, VEGF, BMP-2 and HGF) [ 204 ].…”