Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt; Department of Pharmaceutics, Faculty of Pharmacy and Drug Manufacturing, Pharos University in Alexandria, Alexandria, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Int J Pharm. 2019 Jun 10;564:410-425. doi: 10.1016/j.ijpharm.2019.04.069. Epub 2019 Apr 25.
Albeit its well known potency as a postmenopausal osteoporosis treatment, Risedronate suffers from poor oral bioavailability and high oral toxicity. This is the first work to assess the potential of bilosomes to address challenges of RS oral delivery. Furthermore, impact of integrating cationic moiety into bilosomes on intestinal digestability and toxicity of RS nanovesicles was first investigated in this article. Prepared formulations were optimized based on physicochemical properties, digestibility, intestinal permeation and local toxicity studies. Optimized preparations were prepared by reversed phase evaporation technique with three extrusion cycles and loaded by 10 mg/ml RS. Molar lipid to bile salt to cholesterol ratio was adjusted to 4:1:1 at pH 5. Addition of cholesterol had significantly improved bilosomes stability to digestive media. Results also revealed that permeation of anionic vesicles increased permeation by 1.5 times more than RS solution and reduced drug toxicity by 2 folds. On the other hand, Cationic bilosomes showed good stability in GIT fluids but their induced oral toxicity could limit their use. In conclusion, bilosomes are superior over liposomes regarding protection of delivery system from the damaging effect of external in digestive bile salts. In addition, it decreases toxicity issues of orally administered drugs.
虽然雷洛昔芬作为绝经后骨质疏松症的治疗药物已有广泛的应用，但它存在口服生物利用度差和高口服毒性的问题。本研究首次评估了双层囊泡（bilosomes）在解决雷洛昔芬（RS）口服递送方面的潜力。此外，本文还首次研究了将阳离子部分整合到双层囊泡中对 RS 纳米囊泡的肠道消化性和毒性的影响。根据理化性质、消化性、肠道渗透性和局部毒性研究对制剂进行了优化。优化的制剂是通过反相蒸发技术，经过三个挤出循环，并以 10mg/ml 的 RS 进行装载制备而成。在 pH5 时，将摩尔脂质与胆汁盐和胆固醇的比例调整为 4:1:1。胆固醇的加入显著提高了双层囊泡对消化介质的稳定性。结果还表明，与 RS 溶液相比，阴离子囊泡的渗透增加了 1.5 倍，药物毒性降低了 2 倍。另一方面，阳离子双层囊泡在胃肠道内具有良好的稳定性，但它们引起的口服毒性可能限制了它们的应用。总之，双层囊泡在保护递药系统免受外部消化胆汁盐的破坏作用方面优于脂质体。此外，它还降低了口服药物的毒性问题。
