市售藥劑為改善敏諾西代(Minoxidil)較差的水溶性與增加其皮膚的滲透性，其配方使用化學滲透促進劑（乙醇，丙二醇），每天至少需要兩次塗抹藥劑，以確保它的藥理作用，長期使用這類化學滲透促進劑（乙醇，丙二醇）來增加經皮給藥的效果，會發生異位性皮膚炎。在這項研究中，提供一個新超音波微氣泡顯影劑，可裝載敏諾西代形成水溶液製劑，促進毛髮生長，減少皮膚產生副作用。
以離子逐層吸附法(Layer by layer)使敏諾西代吸附於白蛋白微氣泡(MBs)表面經幾丁寡醣(COL)修飾的陽離子載體(COL-MBs)， 透過DLS量測粒徑與電位、in vitro與 in vivo (n=7)實驗組分別以(1) 控制組(C)、 (2) 單純滲透敏諾西代溶液(Mx)、 (3) 超音波施於敏諾西代溶液(US)、(4) 超音波結合Minoxidil-COL-MBs(US+Mx-COL-MB)、(5)超音波結合Minoxidil混合微氣泡組(US+MB)。
經過幾丁寡醣修飾得到陽離子的微氣泡，其粒徑大小隨球殼不同而改變，依序MBs、COL-MBs與吸附敏諾西代之COL-MBs為1.48，4.15，4.50 µm；表面電位依序為-8.51±0.81、20.23±1.2和0.41±1.73 mV；微氣泡COL-MBs對敏諾西代的吸附率為14.5％；利用FITC觀察經皮穿透深度六小時可達1856 µm，利用透析方式觀察藥物釋放，在2小時時釋放33%；動物實驗中超音波結合COL-MBs吸附敏諾西代組相較控制組提早4天進入生長期，綜合以上結果超音波結合微氣泡之方法能改善敏諾西代之局部治療脫髮症(Alopecias)

A first commercially available formulations of minoxidil which improve its poor water solubility and increase permeability by chemical enhancement methods (ethanol, propylene glycol). The commercially products require at least two times a day to ensure its pharmacological effect, because the products is made of chemical formulations (ethanol, propylene glycol) to increase the ability of transdermal drug delivery so it will often occur atopic dermatitis for long-term use. In this study, a new ultrasound contrast agent, minoxidil loaded microbubbles (MBs) were created and combined with US energy in water-phase to enhance hair growth and reduce the side effects of skin.
The MBs which are layer by layer (LbL) assembly of chitosan oligosaccharide lactate (COL) shell which absorbed minoxidil on this cationic carriers. The zeta potential and size distribution of the minoxidil loaded MBs in suspension were measured by DLS. The in vitro and in vivo experimental parameters will be randomly divided into four groups (n=7 animals per group): (1) no treatment [the control group(C)], (2) only penetrating minoxidil solution(Mx), (3) penetrating minoxidil solution by US(US), (4) US combines minoxidil-COL-MBs(US+Mx-COL-MB), (5)US combines MBs with free minoxidil(US+MB).
The cationic MBs were modified by chitosan. The mean diameters of MBs, MBs coated with COL, and minoxidil loaded COL-MBs were 1.48, 4.15, 4.50 µm. The zeta potentials of MBs, MBs coated with COL and minoxidil loaded COL-MBs were -8.51± , 20.23±1.2 and 0.41 ±1.73 mV, respectively. The loading efficiency of minoxidil on cationic MBs was 14.85%. The penertration depth of FITC was 1856 μm by using ultrasound with microbubbles (6h). The minoxidil release kinetics from minoxidil loaded COL-MBs were determined by dynamic dialysis method. After US treatment, the released rate increased 33% at 2 hour. For the in vivo experiments, the minoxidil loaded MBs would be expected to promote hair growth rapidly 4 days than control group, reduced the treatment dose and side effects. The results confer to these ultrasound with COL-MBs the potential to target and improve topical therapy of alopecia with minoxidil.

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