Translated Abstract
Objective:
Gold nanoparticles are small particle diameter of 1~100 nm, belongs to the high electron dense material. The gold nanoparticles and its particle size can be observed by using transmission electron microscopy (TEM). This experiment of gold nanoparticles were obtained by BPEI reduction method of positive charge on the surface of spherical particles. Gold as a new type of nano technology, with its unique stability, optical properties, chemical properties and biocompatibility of the particle size and its regulation of sex, nanometer gold get corresponding research and development in terms of the tumor. Gold nanoparticles due to the optical properties of surface plasmon resonance, within the scope of visible light has strong absorbency, can effectively converts light energy into heat energy, causing cell mitochondria swelling, protein frozen denaturation, edema, tissue necrosis, etc., this feature is applied to study the selective treatment of cancer cells. Now some research shows that gold nanoparticles can be combined and photosensitizer stability, promote the photosensitizer enter cells, increase the efficiency of the reagents, and the function of itself and also permits efficient inactivated tumor cells, or used in other skin tumor diseases. But the process involved in the mechanism is not clear. Currently, the main medical clinical practice and photosensitizer 5 - amino ketones pentanoic acid, is a kind of endogenous biochemical substances, after cell absorption in ALA dehydration under the action of enzymes and a series of enzymatic, can generate protoporphyrinⅨ, with strong light. 5 - amino ketones pentanoic acid as the second generation photosensitizer is by far the most commonly used exogenous photosensitizer, used for the treatment of severe acne and other skin diseases. 5 - amino ketones pentanoic acid in recent years has also begun in clinic try to used in the treatment of skin cancer. However, 5 - ALA hydrophilic limits its between tissue and cell membrane permeability, which affect the 5 - ALA the absorption and accumulation in tumor cells, and, in turn, affects the treatment effect of photodynamic therapy. Now try to gold nanoparticles coupled with 5 - ALA use, use the biocompatibility of the nanometer gold particles promote cells to absorb 5 - ALA, strengthen its role or 5 - ALA properties of nanometer gold particles, in order to achieve the purpose of more effective in treating diseases, and through the way of transdermal absorption. Transdermal absorption is also called the percutaneous absorption, is refers to the drug by skin absorbs into the skin and subcutaneous tissue in each layer of the lateral or further into the bloodstream. Percutaneous drug absorption can avoid the first effect, thereby reducing the drug adverse reactions, local or system in order to achieve the purpose of controlled release and treatment. Corneous layer is the original position of the transdermal drug delivery, for most drugs, corneous layer is its strong barrier. According to the practical experimental conditions in this experiment using the Er: YAG laser, with minimal energy barrier damage skin cutin layer, changing the morphological structure and arrangement of corneous layer, make gold nanoparticles into the stratum corneum, the gold nanoparticles were discussed through skin absorption, and combined with 5 - ALA together promote the absorption of skin cells to 5 – ALA.
This paper through the gold nanoparticles and 5 - ALA - preparation of nanometer gold combination and analysis of the animal experimental results, proved that the gold nanoparticles can be absorbed through skin, and promote cell to 5 - ALA percutaneous absorption use, for the treatment of skin tumor diseases and tumor diseases research provide a new way of prevention and treatment
Methods:
1) use of BPEI reducing chlorine acid preparation of cationic gold nanoparticles of gold. By electrostatic attraction combines cationic nanometer gold and 5 - ALA, the preparation of 5 - ALA - nanometer gold combination.
2) using the normal kunming mice skin back, nanometer gold particles and 5 - ALA - nanometer gold combination of transdermal absorption in vivo experiments.
3) gold nanoparticles using transmission electron microscopy (tem) observation, observation of gold nanoparticles in the distribution of skin; Using fluorescent microscope 5 - ALA red fluorescence, fluorescence intensity analysis.
Results:
1) under the microscope images of magnified 50000 times to count analysis, under the same concentration, same doses of the drug, nanometer gold particles into the stratum corneum and granular layer cells, under the same concentration, with the extension of time, the number of transdermal absorption of gold nanoparticles increases (P ＜ 0.05), the increasing trend, wipe medicine and wipe medicine 1 hour, 2 hours medicine compared to wipe medicine 2 hours, 3 hours has obvious statistical significance.
2) 5 - ALA group and 5 - ALA - nanometer gold combination by fluorescence microscope Image Pro - Plus software analysis results above show that the same set of experiments, compared with wipe medicine 1 h group, * P ＜ 0.05, compared to wipe medicine 2 h # P ＜ 0.05; The same time, 5 - ALA - nanometer gold compared with 5 - ALA group, combination group & P ＜ 0.05. 5 - ALA group (group A) analysis with medicine 1 h, 2 h, 3 h, the average optical density is 197.96, 212.34, 216.96, respectively, showed A trend of increasing, each group (P ＜ 0.05, there is statistically significant, suggesting 5 - ALA within 3 h growth over time, skin absorption. The same 5 - ALA - nanometer gold combination group (group B) it is concluded that the average optical density is 222.71, 232.52, 240.76, respectively, each group (P ＜ 0.05, there is statistically significant. At the same time, 5 - ALA - nanometer gold combination group compared with 5 - ALA group, each group (P ＜ 0.05, there were significant differences.
Conclusion:
1) in mice in vivo transdermal absorption experiment, cationic gold nanoparticles in the case of destruction of stratum corneum barrier, can through the stratum corneum into cuticle and granular layer cells; Transdermal absorption of 1 h, gold nanoparticles are mainly distributed in the stratum corneum cells clearance and cuticle cells; As the growth of the transdermal absorption time, nanometer gold particles began to be absorbed by the granular layer cells, increase in the number of nanometer gold particles gradually penetrate into the skin, 2 h after corneous layer and granular layer cells can be observed that gold nanoparticles, the increase in the number of gold nanoparticles are also gradually absorbed by the cells.
2) 5 - ALA can through the stratum corneum into skin, under the effect of ALA dehydration enzyme and a series of enzymatic, can generate protoporphyrin IX (protoporphyrin IX, PpIX), transdermal absorption, the longer the greater the amount of 5 - ALA penetrate the skin.
3) 5 - ALA - nanometer gold combination also can breakthrough the barrier of stratum corneum, absorbed by the skin cells to use, because the biocompatibility of the nanometer gold particles, 5 - ALA - nanometer gold combination group compared with pure 5 - ALA solution penetrate into the skin significantly increased 5 - ALA gold nanoparticles with 5 - ALA use electrostatic attraction can promote 5 - after transdermal absorption of ALA.
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