Study On Curcumin-loaded Nanostructured Lipid Carrier Thermosensitive In Situ Gel

Curcumin (Cur) is a natural flavonoid, which is known to have a variety of biological activities and pharmacological actions, such as anticancer, antioxidation, anti-inflammation, anti-anaphylaxis. Recently, curcumin as an antioxidant or anti-inflammation agent has been attracted more and more attentions. However, low solubility and low oral bioavailability of curcumin greatly limit its clinical application.Nanostructured lipid carriers (NLC) as a novel drug delivery system, does not cause skin irritation when applied to the skin topically, and also can improve the degree of hydration of the stratum corneum, thereby increasing the penetration of drugs through the skin. The temperature sensitive in situ gel based on NLC can make NLC be a liquid at room temperature and a semi-solid gel when applied to skin surface, which can prevent the loss of drugs, maintain a longer duration of action and facilitate medication.Curcumin-loaded nanostructured lipid carriers (Cur-NLC) were prepared using the method of emulsification and low-temperature solidification. Then the thermosensitive in situ gel based on Cur-NLC was got by adding the proper concentration of thermosensitive hydrogel matrix to Cur-NLC, which was used to skin topically in order to improve the effects of anti-inflammatory and antioxidation. This study has not been reported in literature.In this study, based on the single factor experiment, orthogonal design was applied to optimize the formulation with entrapment efficiency as index to obtain the optimal preparation and prescription. Physical and chemical properties of the thermosensitive in situ gel based on Cur-NLC were also evaluated. In addition, the enhancement effect of the formulations on the in vitro skin permeation of curcumin and preliminary anti-inflammation effect were assessed. 1. Cur-NLC was prepared with the method of emulsification and low-temperature solidification. The influences of lipid materials, surfactants, liquid oil on the preparation of Cur-NLC were evaluated with single factor experiment. Then the amount of drug, the concentration of surfactant, the amount of co-surfactant and the amount of liquid lipid, proved to have great effects on the properties of Cur-NLC, were selected as influencing factors for the othogonal design to optimize the formulation based on entrapment efficiency of Cur-NLC. The optimal preparation was composed of curcumin30mg, surfactant750mg, co-surfactant200mg, liquid lipid80mg (Total lipid content200mg). Based on this, the concentration of F127was selected at22.5%which could form a semi-solid gel on the skin at32℃.2. Micro-column centrifugation method was used to separate free drug from nanoparticles, and UV spectrophotometry was applied to measure the entrapment efficiency and drug loading of the preparation. The physicochemical property study showed Cur-NLC and its in situ gel formulation were spherically shaped under the transmission electron microscope, and the average particle sizes were263.9nm and277.2nm, respectively. The average encapsulation efficiency were91.77%and90.8%, the average drug loading were2.19%and2.16%, Zeta potential were-18.10mV and-20.3mV, and pH value were4.73and4.79, respectively. The results indicated that the addition of thermosensitive matrix didn’t show significant influence on the physicochemical properties of Cur-NLC.3. Franz diffusion cell was used to study the permeation behavior in vitro. The results showed that the cumulative drug amount penetrating through the excised mouse skin after administration of Cur-NLC and in situ gel formulation were respectively3.02times and2.42times that of Cur-propylene glycol solution as control. The steady-state permeation rates of Cur-NLC and in situ gel formulation and Cur-propylene glycol solution were2.453μg·cm-2·h-1,1.964μg·cm-2·h-1and0.812μg·cm-2·h-1, respectively, which exhibited that Cur-NLC and in situ gel formulation could significantly promote the permeation of drug to skin.4. A preliminary evaluation of pharmacodynamic was conducted in the mouse ear edema induced by xylene inflammatory model, and the results showed that the thermosensitive in situ gel based on Cur-NLC had a good anti-inflammatory effect.