Delivery of Thermoresponsive-Tailored Mixed Micellar Nanogel of Lidocaine and Prilocaine with Improved Dermatokinetic Profile and Therapeutic Efficacy in Topical Anaesthesia.
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 (Tsol/gel), 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.
Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160 014, India.
Gajanand
G
Sharma
Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160 014, India.
Shelly
S
Kamboj
Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160 014, India.
Kanika
K
Thakur
School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh, 173212, India.
Poonam
P
Negi
Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandar Sindri, Distt., Ajmer, Rajasthan, 305 817, India.
Kaisar
K
Raza
Division of Pharmaceutics, University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh, 160 014, India. katare@pu.ac.in.
O P
OP
Katare
D000287:Administration, Topical; D000758:Anesthesia; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D008012:Lidocaine / Q000008:administration & dosage* / Q000737:chemistry*; D051379:Mice; D008823:Micelles; D000080385:Nanogels; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry*; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry*; D011136:Polysorbates / Q000737:chemistry; D011318:Prilocaine / Q000008:administration & dosage* / Q000737:chemistry*; D011817:Rabbits; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects; D014783:Viscosity
D000779:Anesthetics, Local; D008823:Micelles; D000080385:Nanogels; D011136:Polysorbates; C413692:polyethylene glycol polyethyleneimine nanogel; D011318:Prilocaine; D020442:Poloxamer; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D008012:Lidocaine
dermatokinetic; local anaesthetic; permeation; spreadability; thermoresponsive mixed micellar gel; topical anaesthesia