Department of Pharmaceutics, Chandigarh College of Pharmacy, Mohali, Punjab, India.
Nanotechnology Division (H-1), CSIR-Central Scientific Instruments Organization, Chandigarh, 160030, India.
Biomed Pharmacother. 2020 Aug;128:110297. doi: 10.1016/j.biopha.2020.110297. Epub 2020 May 29.
Amphotericin B is a gold standard drug used in various fungal and parasitic infection treatment. Most of the marketed formulations are administered intravenously, but show dose-dependent adverse effects i.e., nephrotoxicity and hemolysis. Oral route eliminates the toxic concern but exhibits poor bioavailability. Therefore, ethylcellulose nanoparticles (EC-NPs) have been used for magnified oral delivery of AmB, where EC provides gastrointestinal stability. These nanoparticles were synthesized by high-pressure emulsification solvent evaporation (HPESE) method and evaluated for in vitro and in vivo studies. This method yields small, monodisperse AmB-EC-NPs along with smooth surface morphology and improved encapsulation efficiency. The developed formulation showed a sustained release pattern following Higuchi diffusion kinetics along with gastric and storage stability. Aggregation study revealed that AmB was present in its monomeric form inside the biocompatible EC matrix. The antifungal result demonstrated that the MIC of AmB-EC-NPs was reduced ∼1/3rd than AmB and Fungizone® at 24 h whereas it was observed ∼1/8th at 48 h. in vivo pharmacokinetic analysis demonstrated 1.3-fold higher AUC than Fungizone® even at a 4.5-time lesser dose via the oral route and a ∼15-fold rise in the bioavailability in contrast to the native AmB. The hemolytic study revealed that the developed formulation exhibited 8-fold lesser hemolysis than Fungizone®. Furthermore, the biosafety profile of AmB-EC-NPs was ensured by the significantly lesser level of blood urea nitrogen and plasma creatinine along with the normal pattern of renal tubules in comparison to AmB and Fungizone®. In conclusion, the results stipulated that the AmB-EC-NPs could be effective, viable and a better alternative to currently existing iv formulations, for magnified oral delivery of AmB in the treatment of fungal infection without associated adverse effects.
两性霉素 B 是一种用于各种真菌感染和寄生虫感染治疗的金标准药物。大多数市售制剂都是通过静脉注射给药，但会表现出剂量依赖性的不良反应，即肾毒性和溶血。口服途径消除了毒性问题，但表现出较差的生物利用度。因此，乙基纤维素纳米粒（EC-NPs）已被用于放大两性霉素 B 的口服递送，其中 EC 提供胃肠道稳定性。这些纳米粒是通过高压乳化溶剂蒸发（HPESE）方法合成的，并进行了体外和体内研究评估。该方法产生小而单分散的两性霉素 B-EC-NPs，同时具有光滑的表面形态和提高的包封效率。所开发的制剂表现出符合 Higuchi 扩散动力学的持续释放模式，以及胃稳定性和储存稳定性。聚集研究表明，两性霉素 B 以单体形式存在于生物相容的 EC 基质中。抗真菌结果表明，两性霉素 B-EC-NPs 的 MIC 比两性霉素 B 和 Fungizone®在 24 小时时降低了约 1/3，而在 48 小时时降低了约 1/8。体内药代动力学分析表明，即使通过口服途径以 4.5 倍的低剂量给药，其 AUC 也比 Fungizone®高 1.3 倍，与天然两性霉素 B 相比，生物利用度提高了 15 倍。溶血研究表明，与 Fungizone®相比，所开发的制剂的溶血率低 8 倍。此外，与两性霉素 B 和 Fungizone®相比，两性霉素 B-EC-NPs 的血液尿素氮和血浆肌酐水平显著降低，肾小管正常，这确保了其生物安全性。总之，结果表明，两性霉素 B-EC-NPs 可能是一种有效的、可行的替代方案，优于目前现有的静脉注射制剂，可用于放大两性霉素 B 的口服递送，以治疗真菌感染，而不会产生相关的不良反应。
