Nageeb El-Helaly Sara, Abd-Elrasheed Eman, Salim Samar A, Fahmy Rania H, Salah Salwa, El-Ashmoony Manal M
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, New Giza University, NewGiza, Km 22 Cairo-Alex Road, Giza 12588, Egypt.
Pharmaceutics. 2021 Apr 1;13(4):474. doi: 10.3390/pharmaceutics13040474.
Green nanotechnology utilizes the principles of green chemistry to formulate eco-friendly nanocarrier systems to mitigate patients and environment hazards. Raloxifene (RLX) demonstrates poor aqueous solubility (BCS class II) and low bioavailability, only 2% (extensive first-pass metabolism). The aim of this study is to enhance RLX solubility and bioavailability via development of novel solid dispersed multilayered core-sheath RLX-loaded nanofibers (RLX-NFs) without the involvement of organic solvents. A modified emulsion electrospinning technique was developed. Electrospinning of an RLX-nanoemulsion (RLX-NE) with polymer solution (poly vinyl alcohol (PVA), hydroxypropyl methylcellulose (HPMC), and chitosan (CS) in different volume ratios (1:9, 2:8, and 4:6) using D-optimal response surface methodology was adopted. In vitro characterization of RLX-loaded NFs was performed; scanning electron microscope (SEM), thermal analysis, drug content, release studies, and bioadhesion potential. The optimum NFs formula was evaluated for morphology using high-resolution transmission electron microscopy (HRTEM), and ex vivo drug permeation. The superiority of E2 (comprising RLX-NE and PVA (2:8)) over other NF formulae was statistically observed with respect to Q60 (56.048%), Q240 (94.612%), fiber size (594.678 nm), mucoadhesion time 24 h, flux (5.51 µg/cm/h), and enhancement ratio (2.12). RLX pharmacokinetics parameters were evaluated in rabbits following buccal application of NF formula E2, relative to RLX oral dispersion. E2 showed significantly higher Cmax (53.18 ± 4.56 ng/mL), and relative bioavailability (≈2.29-fold).
绿色纳米技术利用绿色化学原理来构建生态友好型纳米载体系统，以减轻对患者和环境的危害。雷洛昔芬（RLX）表现出较差的水溶性（BCS II类）和低生物利用度，仅为2%（广泛的首过代谢）。本研究的目的是通过开发新型的固体分散多层核壳载RLX纳米纤维（RLX-NFs）来提高RLX的溶解度和生物利用度，且不涉及有机溶剂。开发了一种改良的乳液静电纺丝技术。采用D-最优响应面法，将RLX纳米乳液（RLX-NE）与不同体积比（1:9、2:8和4:6）的聚合物溶液（聚乙烯醇（PVA）、羟丙基甲基纤维素（HPMC）和壳聚糖（CS））进行静电纺丝。对载RLX的纳米纤维进行了体外表征；扫描电子显微镜（SEM）、热分析、药物含量、释放研究和生物粘附潜力。使用高分辨率透射电子显微镜（HRTEM）对最佳纳米纤维配方进行形态学评估和离体药物渗透研究。在Q60（56.048%）、Q240（94.612%）、纤维尺寸（594.678 nm）、粘膜粘附时间24小时、通量（5.51 µg/cm/h）和增强率（2.12）方面，统计学上观察到E2（由RLX-NE和PVA（2:8）组成）优于其他纳米纤维配方。相对于RLX口服分散体，在兔颊部应用纳米纤维配方E2后评估了RLX的药代动力学参数。E2显示出显著更高的Cmax（53.18±4.56 ng/mL）和相对生物利用度（约2.29倍）。
