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Preparation of Methotrexate Flexible Nano-liposome Gel and Its Clinical Efficacy on Treating Eczema

Author: ShengXiaoZuo
Tutor: YaoYao；DingJinSong
School: Central South University
Course: Pharmacy
Keywords: Methotrexate Flexible nano- liposomes Gel External use Eczema
CLC: R94
Type: Master's thesis
Year: 2011
Downloads: 66
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Abstract

Purpose methotrexate (Methotrexate, MTX) is a folic acid analogue, can be competitive inhibition of dihydrofolate reductase, which interfere with DNA and RNA synthesis tetrahydrofolate hindered. Small dose oral MTX immunosuppressive activity and anti-inflammatory effects, can be used to treat atopic eczema, senile generalized eczema, atopic dermatitis delayed or primary eczema and adult eczema and other severe, but its obvious hepatotoxicity seriously affect its widespread use. Consider the skin disease is mainly localized inflammatory lesions, local administration should have better prospects. This article through the study of the physical and chemical properties of MTX, build, and preliminary evaluation the the MTX flexible nanoliposome (Flexible Nano-liposomes, FNL) gel, comparison with the same concentration ordinary gel to reduce the amount of drug penetration, improve skin retention the advantages of; the observed MTX-FNL gel on the efficacy and safety of clinical eczema treatment, to explore the feasibility of the topical treatment of eczema and reasonable form applicators, to lay the foundation for the development of the MTX topical treatment of eczema. The results will also provide reference MTX topical treatment of psoriasis and other skin diseases. Method results 1.MTX physicochemical nature and encapsulation Determination method to establish the MTX content determination method and was measured at 25 ℃, MTX solubility in aqueous solutions of different pH and oil / water partition coefficient. MTX solubility and oil / water partition coefficient is governed by pH. The 25 ℃ slightly soluble in water, slightly soluble in pH7.4 PBS solution (10.856 ± 0.127mg · ml-1), the poor lipophilicity, logP less than -1.43 (pH = 6.8). Construction and characterization of MTX-FNL by reverse phase evaporation prepared MTX-FNL, encapsulation efficiency and particle size evaluation index by single factor screening phospholipid dosage phospholipid-CH (w / w), membrane softening dosage, oil-water volume ratio, hydration time prescription process factors determine the prescription process by orthogonal design and a particle size of 212.70 3.93 nm, and the encapsulation efficiency was 25.62 ± 0.18% of MTX-FNL suspension. The suspension at room temperature and 4 ° C for 10 d, and basically stable. 3. MTX-FNL in vitro percutaneous penetration studies established HPLC method for the determination of MTX received the in vitro percutaneous penetration test liquid and skin concentration, the high specificity of the method, does not interfere with the determination of endogenous substances in the skin . Using modified Franz diffusion cell research the impact of the of the the two membranes softener amount of MTX-FNL piglet skin in vitro vitro percutaneous permeation behavior. The results show that the Doc-Na and the amount of KG percutaneous penetration behavior of liposomes has a significant effect on cumulative permeation amount (Q24) 24 h per unit area, with the increase in the amount of membrane softeners, no significant difference (P gt; 0.05) 24 h per unit mass of skin retention (Qskin) increased (P gt; 0.05). The binding prescription screening result, when the phospholipid-kg ratio (w / w) of 10:1, liposomes, and the lower MTX permeation amount, higher skin retention. Therefore, in the subsequent liposome gel Construction, selection kg (with phospholipid ratio (w / w) of 10:1) as a film softener. The MTX-FNL gel and quality evaluation build a 0.25% MTX-FNL gel 0.0625% the MTX-FNL gel (using the minicolumn centrifugation to remove liposome suspension free drug preparation FNL gel ) and the same concentration of the ordinary gel, investigated in vitro piglet skin vitro percutaneous permeation behavior. The results show that the Q24 FNL gel concentration was significantly higher than the normal gel (P lt; 0.05) the Qskin are higher than the the ordinary gel, about 2 times, and the differences were significant sex (P lt; 0.05). The FNL gel can significantly reduce the Q24 of MTX improve Qskin, suggesting that it may have a better therapeutic effect on eczema. Select 0.25% MTX-FNL gel clinical eczema treatment efficacy and safety inspection. 5 the MTX-FNL skin irritating and preliminary clinical efficacy of single, many times to give 0.25% MTX-FNL gel had no irritation rabbit normal and damaged skin. Observed 0.25% MTX-FNL gel with the exact efficacy Halometasone triclosan ointment (ie new fitness indeed have ointment) treatment of the efficacy and safety of eczema, the results of the treatment group and the control group after treatment EASI score and pruritus scores There was no significant difference (P gt; 0.05) shows that the treatment group was almost up to the control group treatment effects, and adverse reactions were not observed in the two groups in the treatment period. MTX-FNL whether stranded skin local efficacy play remains to be further confirmed. Third, the poor water-soluble and percutaneous penetration ability of the conclusions MTX the FNL technology can improve MTX percutaneous penetration ability, and can significantly reduce the amount of permeability, improve skin holdup; single, repeatedly given 0.25% MTX- FNL gel normal rabbits and damaged skin were not irritating; 0.25% MTX-FNL gel with triclosan Halometasone ointment listed the eczema almost have considerable therapeutic effect, and no adverse reactions during the observation period. The MTX-FNL retention position within the skin and the amount and treatment of the relationship between eczema efficacy remains to be further studied.

Preparation of Methotrexate Flexible Nano-liposome Gel and Its Clinical Efficacy on Treating Eczema

Abstract

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