Capsaicin Loaded Nanolipoidal Carriers For Topical Application:Design,Characterization And In Vitro/in Vivo Evaluation

Objective:In this study, we constructed a nanolipoidal carriers (NLCs) system for topical drug delivery of capsaicin. Furtherly, apply the single factor analysis method and Box-Becken design to optimize the prescription in order to improve the percutaneous permeation ability and achieve the anti-inflammatory, analgesic effect of the capsaicin-based formulations with lower skin irritation.Methods:1.Apply the single factor analysis method to select the factors which have an impact on the response values.2.Utilize the Box-Becken design to optimize the prescription and get the optimum prescription then synthetize the capsaicin-loaded nanolipoidal carriers (capsaicin-loaded-NLCs) and study the physicochemical properties and in vitro release profile of capsaicin-loaded-NLCs.3.Study the cytotoxicity of capsaicin free drug and capsaicin-loaded-NLCs on skin cells.4.The percutaneous permeation study and capsaicin distribution in different skin layers were conducted. Furthermore, substitute Dio for capsaicin to examine the penetration depth of the drug and the main transdermal route of the NLCs.5.The analgesic and anti-inflammatory effects of capsaicin-based formulations were determined by the hot-plate test and carrageenan-induced paw edema.6.Evaluate the skin irritation of capsaicin-based formulations.7.Cryoprotectors for capsaicin-loaded-NLCs freeze-dried powder were screened and the capsaicin-loaded-NLCs freeze-dried powder was synthetized.Results:The prescription was optimized by 15-runs,3-factors,3-level Box-Becken design. The three factors choiced were solid lipid and liquid lipid ratio, total amount of lipids and amount. The compositions of optimum formulation were 500 mg solid lipid, 360 mg liquid lipid and 360 mg Tween 80. The capsaicin-loaded-NLCs showed milky white with opalescent. The entrapment efficacy, zeta potential and average particle size of capsaicin-loaded-NLCs were 91.6±1.3%,-17±0.4 mV and 119±4 nm, respectively. Capsaicin-loaded-NLCs showed a sustained release of more than 48 h. According to the MTT assay and apoptosis experiment, capsaicin-loaded-NLCs did not showed obvious cytotoxicity which meant that it was safe to be used. After 24 h percutaneous permeation study, cumulative drug permeated were 29.7 μg. cm-2 and 25.6 μg. cm-2 for capsaicin-loaded-NLCs and capsaicin-loaded-NLCs-Gel which were significantly higher than the 17.9 μg. cm-2 and 2.2 μg. cm-2 for capsaicin-Cream and capsaicin-Solution. The permeation flux rate of capsaicin-loaded-NLCs and capsaicin-loaded-NLCs-Gel were 14.4- and 12.2-folder faster than capsaicin-Solution. Those results meant that NLCs could enhance the cumulative permeation amount and permeation flux rate of capsaicin. Skin retention study showed that NLCs could improve the distribution of capsaicin in epidermis and dermis. What’s more, NLCs could improve the penetration depth of the drug which was mainly through the appendages route. According to the in vivo therapeutic study, capsaicin-based formulations showed analgesic effect and anti-inflammatory effects by inhibiting the PGE2 level. Skin irritation test revealed that NLCs can reduce the irritation of the capsaicin. The freeze-dried power used 2% sucrose and 2% glucose as the cryoprotectors. It had good redissolution ability and the morphology was not changed as well.Conclusion:the capsaicin-loaded-NLCs and capsaicin-loaded-NLCs-Gel were promising topical delivery formulations which showed delightful percutaneous permeation ability and could achieve the analgesic and anti-inflammatory effect with the reduction of the skin irritation.