Muta Thabata, Parikh Ankit, Kathawala Krishna, Haidari Hanif, Song Yunmei, Thomas Jackson, Garg Sanjay
Pharmaceutical Innovation and Development Group (PIDG), UniSA Clinical & Health Science, University of South Australia, City West Campus, North Terrace, Adelaide, SA 5000, Australia.
Faculty of Health, University of Canberra, Canberra, ACT 2617, Australia.
Pharmaceutics. 2020 Nov 13;12(11):1091. doi: 10.3390/pharmaceutics12111091.
Despite the promising properties of tea tree oil (TTO) as potential therapeutics for several superficial skin conditions, certain limitations such as physical instability and skin irritation have restricted its widespread use. This study focuses on developing a rationally designed lipid-based nanoformulation (TTO-LNF) in accordance with the US Food and Drug Administration standard using a well-recognized quality-by-design (QbD) approach. Using a mixture experimental design, TTO-LNF has been optimized with 5% TTO, 10% surfactant, 5% co-surfactant, and 80% water, which showed a 14.4 ± 4.4 nm droplet size and 0.03 ± 0.01 polydispersity index (PDI). To ease the topical administration, the TTO-LNF gel formulation was further developed using xanthan gum to achieve the desired viscosity and form a gel. The in vitro antibacterial tests of TTO-LNF showed promising inhibitory effects toward both Gram-negative and Gram-positive bacteria. In fact, a complete growth inhibition of was observed when exposed to TTO-LNF and TTO-LNF gel for 24 h, showing better activity than antibiotic kanamycin (25 µg/mL). Additionally, the in vitro release study showed a sustained release profile with a 50% release in 24 h, which could be beneficial to reduce the toxicity and thereby improve the therapeutic efficacy for long-acting applications. Furthermore, the formulations were remarkably stable at 40 °C/75% Relative humidity (RH) for at least 4 weeks. Therefore, this study presents a promising strategy to develop a biocompatible and stable formulation that can be used for the topical treatment of skin infections.
尽管茶树油（TTO）作为多种浅表皮肤疾病的潜在治疗药物具有良好的特性，但诸如物理稳定性和皮肤刺激性等某些局限性限制了其广泛应用。本研究聚焦于根据美国食品药品监督管理局的标准，采用公认的质量源于设计（QbD）方法，合理设计基于脂质的纳米制剂（TTO-LNF）。使用混合实验设计，TTO-LNF已通过5% TTO、10%表面活性剂、5%助表面活性剂和80%水进行了优化，其液滴尺寸为14.4±4.4纳米，多分散指数（PDI）为0.03±0.01。为便于局部给药，进一步使用黄原胶开发了TTO-LNF凝胶制剂，以达到所需粘度并形成凝胶。TTO-LNF的体外抗菌试验对革兰氏阴性菌和革兰氏阳性菌均显示出有前景的抑制作用。事实上，当暴露于TTO-LNF和TTO-LNF凝胶24小时时，观察到完全生长抑制，显示出比抗生素卡那霉素（25微克/毫升）更好的活性。此外，体外释放研究显示出持续释放曲线，24小时内释放50%，这可能有利于降低毒性，从而提高长效应用的治疗效果。此外，制剂在40℃/75%相对湿度（RH）下至少4周内非常稳定。因此，本研究提出了一种有前景的策略，可开发一种生物相容性和稳定性良好的制剂，用于皮肤感染的局部治疗。
