Nawaz Maubashera, Hayat Sofia, Farooq Umer, Iqbal Muhammad Adnan, Khalid Syed Haroon, Nee Tan Wen, Khaw Kooi Yeong, Munir Rabia, Ijaz Muhammad Umar
Department of Chemistry, University of Agriculture Faisalabad 38040 Pakistan
Department of Pharmaceutics, Government College University Faisalabad 38000 Pakistan.
RSC Adv. 2024 Oct 10;14(44):32008-32020. doi: 10.1039/d4ra04816d. eCollection 2024 Oct 9.
The current study focuses on assessing the activity of the -alkylated benzimidazole based cubosomal hydrogel (cubogel) for the topical treatment of burn wounds. The study involves the synthesis of six benzimidazole derivatives (1-6) and their characterization by FT-IR and H and C NMR spectroscopy. The further study involves the design and formation of nanoparticles known as cubosomes loaded with selected 1-benzyl-1-benzimidazole (API 6) and the development of a cubogel for the topical treatment of burn wounds. Cubosomes were prepared by the homogenization method, using glyceryl monooleate (GMO) as a lipid polymer and poloxamer 407 (P407) as a surfactant. Cubosomes undergo characterizations (measurement of particle size, zeta potential, polydispersity index (PDI), % entrapment efficiency, drug release in phosphate buffer saline of pH 6.8, and surface morphology by utilizing TEM (transmission electron microscopy). Formulation D3 (2.5% of GMO, 1% of P407, and 2.5% of PVA) emerged as the optimized formulation, displaying a minimum particle size (PS) of 129.9 ± 1 nm, entrapment efficiency (%EE) of 96.67 ± 0.89%, and a drug release of 86 ± 2.7% at 24 h. Carbopol 940 hydrogel was prepared and incorporated with the optimized formulation to prepare cubogel. This optimized cubogel provided 92.56 ± 0.014% drug release within 24 h. An histopathological study was conducted on an animal model (rabbit) to assess the efficacy of cubogel in wound healing and wound contraction. Then cubogel was compared with the commercially available creams Clotrimazole® and Polyfax®. The wound treated with newly developed cubogel has maximum wound contraction (96.70%) as compared to the standard creams. The findings revealed that the newly formulated cubogel was highly effective in treating burns, showing superior performance to commercial products without inducing side effects. Additionally, benzimidazole derivative loaded cubogel caused a sustained release for treating burn wounds without any bacterial infections. The current results further suggested phase 0 clinical trials.
当前的研究聚焦于评估基于烷基化苯并咪唑的立方液晶纳米粒水凝胶（立方凝胶）用于烧伤创面局部治疗的活性。该研究涉及六种苯并咪唑衍生物（1 - 6）的合成及其通过傅里叶变换红外光谱（FT - IR）、氢核磁共振（¹H NMR）和碳核磁共振（¹³C NMR）光谱进行的表征。进一步的研究包括设计和形成负载选定的1 - 苄基 - 1 - 苯并咪唑（活性成分6）的纳米粒，即立方液晶纳米粒，以及开发用于烧伤创面局部治疗的立方凝胶。立方液晶纳米粒通过均化法制备，使用单油酸甘油酯（GMO）作为脂质聚合物，泊洛沙姆407（P407）作为表面活性剂。对立方液晶纳米粒进行表征（测量粒径、zeta电位、多分散指数（PDI）、包封率、在pH 6.8的磷酸盐缓冲盐水中的药物释放，以及利用透射电子显微镜（TEM）观察表面形态）。配方D3（2.5%的GMO、1%的P407和2.5%的聚乙烯醇（PVA））成为优化配方，显示出最小粒径（PS）为129.9±1纳米，包封率（%EE）为96.67±0.89%，以及在24小时时药物释放率为86±2.7%。制备了卡波姆940水凝胶，并与优化配方混合以制备立方凝胶。这种优化的立方凝胶在24小时内药物释放率为92.56±0.014%。在动物模型（兔子）上进行了组织病理学研究，以评估立方凝胶在伤口愈合和伤口收缩方面的疗效。然后将立方凝胶与市售乳膏克霉唑乳膏（Clotrimazole®）和聚法克斯乳膏（Polyfax®）进行比较。与标准乳膏相比，用新开发的立方凝胶治疗的伤口具有最大的伤口收缩率（96.70%）。研究结果表明，新配制的立方凝胶在治疗烧伤方面非常有效，表现出优于市售产品的性能且无副作用。此外，负载苯并咪唑衍生物的立方凝胶在治疗烧伤创面时能实现持续释放且无任何细菌感染。当前结果进一步提示进行0期临床试验。
