Construction And Evaluation Of Transdermal Drug Delivery System Of Ganoderma Lucidum Triterpene Nano - Gel In Difficult Part Of Traditional Chinese Medicine

In order to enhance water solubility and transdermal absorption of drugs with poor water solubility and improve the stability, moisture and adhesion of NS, a novel nanogel was developed by combining the advantages of NS and gel in this paper. The triterpenoids isolated from Ganoderma lucidum (GLT) were chosen as model drug and studied systematically.The GLT-NS was prepared by high pressure homogenization. The preparation process of GLT-NS was optimized by employing single factor experiment with particle size and polydispersity index (PDI) as indexes. The optimum preparation process of GLT-NS as follows:1.0 g Tween 80 and 0.5 g Poloxamer F68 were completely dissolved in 100 mL water to obtain a stabilizer solution.6.5 g GLT were dispersed in the obtained stabilizer solution. The obtained dispersion was firstly processed using a high shear homogenizer at 13000 rpm for 5 min and then homogenized at high pressure (ten cycles at 500 bar firstly and then 20 cycles at 1200 bar) using a piston-gap high pressure homogenizer to produce GLT nanosuspensions. The particle size, PDI and zeta potential of the optimized GLT-NS were (283±7) nm, 0.1710±0.0150, and (-32.1±2.6) mV, respectively. SEM images revealed that GLT was appeared to be irregular with particle size of 5～50 μm, while the GLT-NS prese- nted a granular shape. Stability test showed GLT-NS stored at room temperature was instability caused by particle growth and aggregation.The GLT nanogel was prepared by direct swelling method. The formulations of GLT nanogel were optimized by employing Box-Behnken design-response surface methodology with the amount of carbopol 940, drug and propylene glycol as investigation factors, and cumulative release of drug from the GLT nanogel within 24 h and particle size of reconstituted nanoparticles from GLT nanogel as indexes. The optimum preparation of GLT nanogel with drug loading of (22.93±0.35) mg·g-1 as follows:0.5 g carbopol 940 swelled in an appropriate amount of water and then added into 46 mL GLT-NS,14.2 g propylene glycol under condition of stirring using a magnetic stirrer. The 20%(v/v) triethanolamine was then added and the pH was adjusted to 5.5～6.5. Finally, an amount of distilled water was added to adjust to 100 g. The cumulative release of drug from the GLT nanogel within 24 h, particle size of reconstituted nanoparticles from GLT nanogel, PDI and zeta potential of optimized GLT nanogel were (62.48±1.79)%,(297±8) nm,0.1820±0.0130 and (-42.3±3.7) mV, respectively. The pH of GLT nanogel was found to be 6.07±0.10, which was within acceptable limits. Stability studies showed that GLT nanogel storage at room temperature for 120 days exhibited good stability.The in vitro permeation study and in vivo anti-frostbite efficacy of GLT nangel were studied and compared to that of GLT gel in this paper. The amounts of GA penetrating through the skin and in the skin after applying the optimum GLT nanogel and GLT gel for 24 h were (52.37±6.74)μg·cm2, (20.84±4.13)μg·cm2 and (98.26 ±9.19)μg·cm2, (25.07±4.57)μg·cm2, respectively. The amount of GA permeated through skin of GLT nanogel after 24 hours was 2.51-fold higher than GLT gel (P<0.05), and GLT nanogel increased the accumulative amount of GA in epidermis 3.92 times than GLT gel (P<0.05). The results of pharmacodynamic study indicated that the GLT nanogel was more effective than GLT gel in the treatment of frostbite at the same dose. The results of the skin irritation study indicated that GLT nanogel exhibited no irritation to intact skin.In summary, GLT nanogel could significantly improve the in vitro transdermal absorption, retention in skin and frostbite treatment. Therefore, the combination of NS and gel that applied to delivery poorly soluble active parts of Traditional Chinese Medicine is an effective method for enhancing transdermal absorption and pharmacodynamic efficacy of poorly soluble active parts of Traditional Chinese Medicine.