| Photodynamic therapy(PDT) created in the1970s, in recent years due to development and progress of the photosensitive material, PDT has gradually become one of the basic means ot treatmeng of cancer, its treatment based on first to give the body the photosensitizer which can be intaked selectivity by the tumor tissue,then use the laser light with a specific wavelength to irradiate the tumor tissue,inducephotochemical reaction of photosensitizer to generate the very reactive singlet oxygen,and thus the oxidation reaction with biological macromolecules and,resulting in cytotoxicity to kill cancer cells(and display treatment effect).The biggest advantages compared with traditional tumor therapy such as surgery, radiotherapy,chemotherapy and immune therapy,photodynamic therapy is the selective destruction of the cancer tissue and fewer side effects. Since1990Canadian scholars Kennedy for the first time used5-aminolevulinic acid(5-ALA) in tumor ablation therapy,5-ALA has gradually become the most common clinical photosensitizer.As the second generation photosensitizer,5-ALA is an endogenous photosensitizer because of it has less side effects, definite effect,and has been widely used in tumor, pre-cancerous.And non-neoplastic skin diseasestreatment,there are more applications have been reported in certain proliferative disease, viral disease and inflammatory disease’s treatment and beauty and light tender skin.5-ALA is polar components, low permeability skin, make it very difficult to achieve target parts of the skin tissue. In the clinical treatment is usually adopts the high concentration of20%5-ALA, but60%-80%of clinical patients will produce light toxicity side effects.If by enhancing the permeability of5-ALA is able to improve the efficiency of photodynamic therapy to reduce their dosage,it is possible to reduce the incidence of phototoxicity.Liposomes as drug carriers for improving transdermal drug absorption, reduce the side effects can have better effect. Part of the hydrophilic drugs through the combination of phospholipids and improve the liposolubility, enhance the skin and tissue penetration, thereby enhancing the pharmacological function, improve the bioavailability, through the preparation5-ALA liposomes can increase the skin through rate into the target tissue and give full play to its curative effect.Liposomes including phospholipids, cholesterol,has the good biological compatibility can promote drug transdermal absorption of increase drug cuticle through the amount and retention in the skin, enhance skin targeting, reduce local adverse reaction; It has the enhancement drugs into the corneous layer and skin in the lipid role; And can greatly reduce the penetration into the blood circulation, reduce systemic side effects. As a main component, phosphplipids have a high degree of similarity with the skin stratum, and the good biocompatibility, has a protective effect on the skin. Liposomes as a drug carrier due to the characteristics of its composition and structure, formed a new route of administration and skin care concept.Considering the5-ALA hydrochloride had good water solubility, in order to get higher encapsulation efficiency,this experiment used the film-pH gradient method of preparation of5-ALA liposome, lay the foundation for the next steo related research.,and the composition and preparation technology. Then prepared the5-ALA liposome gel and began its basic inspection. The first pare set up the content determination of ultraviolet spectrophotometry and high performance liquid chromatography,which due to5-ALA and lipid in ultraviolet absorption in the mutual interference,finally to adopt the high performance liquid chromatography(HPLC) method to detrrmine the content of the5-ALA. Hypersil ODS column (4.6x250mm,5μm); The column temperature was25℃; Mobile phase50mmol·L-1(NH4) H2PO4(pH2.2)/methanol=98/2. UV detected wavelength was267nm, flow rate was0.0mL·min-1. There was a good linear relationship between concentration and peak area, accord with the analysis request.The second pare adopts the glucan G-50gel chromatography separating liposomes and free drug, established the UV, HPLC method for the determination content,and with the encapsulation efficiency for index of single factor investigation, determined the basic prescription and liposome technology of the5-ALA, investigated phospholipid cholesterol mass ratio of drug to lipid ratio and incubation temperature on the encapsulation efficiency, determined the best prescription, Lecithin and cholesterol than those for the quality, lecithin and5-ALA than those for quality, incubation temperature of60℃,the average encapsulation efficiency of the best prescription is65.0%The third part determined the best prescription, inspected the liposome form, particle size and size distribution of evaluation indexes, etc. Morphology is mainly observation and negative staining, its appearance of the liposome is round sphere, oval, or irregular chondrules;5-ALA liposome average particle size is100nm, polydispersity index(PI) is0.224, the particle size distribution is uniform;5-ALA liposome with low negative charges, average Zeta potential-40.6mv, more stable.The fourth part determined the5-ALA liposome gel preparation method. Investigated the appearance of the liposome gel, centrifugal sedimentation, viscosity and other indexs, the results showed that the preparation of liposome gel is feasibility. According to the Chinese pharmacopoeia release determination comparisonof in vitro release of the liposomal gel and5-ALA gel. |
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