近年有研究發現超音波可以促進傷口周圍細胞活化加速傷口癒合，本研究以新型抗菌超音波微氣泡對比劑作為藥物釋放載體，在微氣泡表面修飾表皮生長因子(EGF)添加於一般市售敷料並施打超音波所產生的穴蝕效應，加強促進藥物在傷口之真皮層與皮下組織細胞吸收加速傷口癒合。
本研究以電性吸附法使表皮生長因子(EGF)吸附於溶菌酶微氣泡(LYMBs)，透過DLS量測粒徑與電位並進行離體(in vitro)抗菌實驗(n=3)與活體(in vivo) (n=5)動物實驗。抗菌實驗組分別為(1) 控制組(C)、(2) 超音波結合控制組(C+U)、(3) Lysozyme溶液組(L)、(4) 超音波結合Lysozymes溶液組(L+U)、(5) LYMBs組(M)、(6) 超音波結合LYMBs組(M+U)、(7) EGF-LYMBs組(EM)、(8) 超音波結合EGF-LYMBs組(EM+U)。動物實驗組分別為(1) 控制組(C)與超音波結合控制組(C+U)、(2) 單純敷料組(D)與超音波結合單純敷料組(D+U)、(3) LYMBs搭配敷料組(M)與超音波結合LYMBs搭配敷料組(M+U)、(4) EGF溶液搭配敷料組(E)與超音波結合EGF溶液搭配敷料組(E+U)、(5) EGF-LYMBs搭配敷料組(EM)與超音波結合EGF-LYMBs搭配敷料組(EM+U)。
表面吸附EGF得到的溶菌酶微氣泡，吸附前後其粒徑大小會隨之改變，依序LYMBs、EGF-LYMBs為2.68 ± 0.21 μm、3.78 ± 0.18 μm；表面電位依序為80.33 ± 1.19 mV、40.33 ± 3.62 mV；微氣泡LYMBs對EGF的吸附率為19.40%；利用透析方式搭配超音波觀察藥物釋放，在2小時時釋放44%；抗菌實驗結果中與C+U(18.23%)、L(75.12%)、M(96.56%)相比，3 W/cm2超音波結合溶菌酶微氣泡(M+U)擁有最好的殺菌效率(97.50%)。動物實驗結果中超音波結合EGF-LYMBs組相較於其他組別在傷口修復上的效果是最好的，綜合以上結果3 W/cm2超音波結合修飾表皮生長因子微氣泡能有效加強傷口之修復率。

In previous studies, ultrasound (US) can induce cell activation around the wound to accelerate wound healing. In this study, a new antibacterial US microbubbles (MBs) as a drug delivery vehicle, loaded with epidermal growth factor (EGF) added to the dressing combines with US was provided to accelerate wound healing.
The Lysozyme-shelled MBs (LYMBs) absorbed EGF on this cationic carriers. The zeta potential and size distribution of the EGF loaded LYMBs in suspension were measured by DLS. The in vitro, anti-bactericidal experiment for S.aureus and in vivo experiments were performed. The experimental parameters of anti-bactericidal experiment for S.aureus will be divided into eight groups (n=3): (1) the control group(C), (2) US combines control group(C+U), (3) only Lysozyme solution(L), (4) US combines Lysozyme solution(L+U), (5) only LYMBs(M), (6) US combines LYMBs(M+U), (7) only EGF-LYMBs(EM), (8) US combines EGF-LYMBs(EM+U). The in vivo experimental parameters will be randomly divided into five groups (n=5 animals per group): (1) no treatment [the control group(C)] and US alone(C+U), (2) only dressing(D) and US combines dressing(D+U), (3) LYMBs in dressing(M) and US combines LYMBs in dressing(U+M), (4) EGF solution in dressing(E) and US combines EGF solution in dressing(E+U), (5) EGF-LYMBs in dressing(EM) and US combines EGF-LYMBs in dressing(U+EM).
The cationic LYMBs were absorbed by EGF. The mean diameters of LYMBs and EGF-LYMBs were 2.68 ± 0.21 μm and 3.78 ± 0.18 μm, respectively. The zeta potentials of LYMBs and EGF-LYMBs were 80.33 ± 1.19 mV and 40.33 ± 3.62 mV, respectively. The loading efficiency of EGF on cationic LYMBs was 19.40%. The EGF release kinetics from EGF loaded LYMBs were determined by dynamic dialysis method. After US treatment, the released rate increased 44% at 2 hours. The results of anti-bactericidal experiment for S.aureus showed the best anti-bactericidal effect (97.50%) at a power density of 3 W/cm2 combined with the LYMBs(M+U) higher in than those in groups C+U(18.23%), L(75.12%) and M(96.56%). The results of in vivo experiments showed the best wound healing effect at a power density of 3 W/cm2 combined with the EGF-LYMBs(EM+U) higher in than other groups. The results confirmed that US combined with EGF-LYMBs can enhance wound healing.

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