| Psoraleary is the dried fruit of leguminous Psoralen croylifolia L,which has good effect in the treatment of vitiligo.There are many reports show that Isopsoralen(IPRN)is the main active ingredient of psoralen in the treatment of vitiligo,but IPRN is dissoluble in water and cannot be absorbed by the skin which results a low retention in the epidermal layer of the skin.As a result,the low bioavailability of IPRN greatly restricts its clinical application.In this paper,IPRN-NLC was prepared,which not only enhanced the drug loading,but also improved hydration with the skin and promoted transdermal absorption of drugs and increased the retention of skin.Taking into account the stability of the IPRN-NLC and the ease of use,IPRN-NLC-gel was prepared.The results are as follows:(1)IPRN-NLC was prepared by high pressure homogenization and optimized by orthogonal experiment with the encapsulation efficiency,drug loading and average particle size as the evaluation indexes.The best preparation of IPRN-NLC are as follows: 1.05 g ATO888 and 0.45 g MCT were heated up to 77℃,then 50 mg IPRN was dissolved in the lipid melt.The water contains 0.67 g and was dispersed into the lipid phase of the same temperature by stirrer at 1200 r/min for 0.5 h.The obtained pre-emulsion was sheared at 10000 r/min last 1 minute for three times,and then pass the high pressure homogenizer for 6 cycles at 880 bar.After cooling at room temperation,the IPRN-NLC dispersion was obtained.The average particle size was(305.0 ± 15.7)nm,PI was(0.28 ± 0.02),Zeta was(-27.20 ± 0.68)and the average entrapment efficiency and drug loading were(90.25 ± 0.73)% and(1.56 ± 0.27)% of the optimized IPRN-NLC.Scanning electron microscopy(SEM)onfirmed IPRN-NLC was spherical shape,while the IPRN was needle.The XRD results showed that IPRN existed in the amorphous state in NLC.Furthermore,IPRN-NLC was stable in 30 days,but would precipitate during the long-term storage.(2)The vitro evaluations of IPRN-NLC were performed.The in vitro skin permeation study revealed that the retention of IPRN-NLC was about 3 times compared to IPRN suspension.The IPRN-NLC could significantly promote the proliferation,tyrosinase activity and melanin content compared with IPRN-DMSO groups at the same concentration.(3)Direct swelling method was used to prepare the IPRN-NLC-gel.The IPRNNLC-gel was optimized by Box-Behnken design with acculation penetration and retention in skin at 24 h as the indicators,which based on single factor test.The optimum preparation of IPRN-NLC-gel are as follows: 0.75 g carbomer 940 was swelled by IPRN-NLC dispersion and 11.13 g glycerin for about 24 h,and then add appropriate amount of distilled water to 100 g.After stiring,the 20% triethanolamine was added to adjust the pH to 5.5~6.5,then the 0.18 mg/g of IPRN-NLC-gel was obtained.The nanoparticle size was(315 ± 10)nm,PI was(0.23 ± 0.03),Zeta was(-30.70 ± 0.26),pH was(6.15 ± 0.13),and viscosity index of IPRN-NLC-gel was(3216 ± 12),which met the standards of topical gel.IPRN-NLC-gel showed good stability when storaged at room temperature for 90 days.The result of in vivo transdermal test found that the retention of IPRN-NLC-gel was(1.28 ± 0.01)in skin,while IPRN-gel was(0.54 ± 0.01),which showed that NLC-gel could improve the retention of IPRN in the skin.The results of in vitro dissolution showed that IPRN-NLC exhibited faster release at first and a sustained drug release of 65.49% over 48 h as compared to IPRN suspension only showed 53.65%,which significantly increased the saturation solublity and dissolution of the drug;IPRN-NLC-gel was 58.19%,examining that the gel could prevent drug from release.In summary,the skin penetration and retention of IPRN was improved by IPRNNLC-gel,so the bioavailablility of the drug was increased.Therefore,the insoluble active ingredients of Traditional Chinese Medicine can be made into NLC-gel,which is an effective method for improving the bioavailability of poorly soluble ingredients for transdermal delivery. |
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