Development of progesterone electrospun nanofibers to coat Arabin pessaries as a dual preventive and therapeutic approach for preterm labor.

Preterm labor is a growing health problem that causes newborn death, and safe and effective therapy is significantly needed. Arabin pessaries and progesterone are preventive and therapeutic approaches that can be applied to managing the short cervix; hence, reducing the risk of preterm labor. The main goal of current work is to fabricate a novel nanofiber formulation based on polycaprolactone (PCL) and loaded with progesterone to coat for Arabin pessaries to be used as dual preventive and therapeutic approaches for local vaginal delivery. Several important criteria were considered in this study to assess the prepared nanofibers (i.e.; nanofiber diameter, progesterone loading efficiency, progesterone release profiles and in vitro cytotoxicity assessment). The results showed a dimeter of 397 ± 88 nm, drug loading of 142 ± 3 µg/mg and encapsulation efficiency of 99 ± 2 % for the progesterone-loaded nanofibers. Approximately, 17 % of progesterone was released from the nanofibers after 90 days. The in vitro assessment showed that the application of progesterone is safe upon 24 and 48-hours incubation on HFF-1 cell line at concentrations ≤ 32 µg/mL and within 72-hours at a dose of ≤ 8 µg/mL. To conclude, the data recommended that progesterone-loaded nanofibers can coat the Arabin pessaries with the potential of being a safe and effective dual preventive and therapeutic tool for preterm labor.

GL67 lipid-based liposomal formulation for efficient siRNA delivery into human lung cancer cells.

The efficient delivery of small interfering RNA (siRNA) to the targeted cells significantly affects the regulation of the overexpressed proteins involved in the progression of several genetic diseases. SiRNA molecules in naked form suffer from low internalization across the cell membrane, high susceptibility to degradation by nuclease enzyme and low stability, which hinder their efficacy. Therefore, there is an urge to develop a delivery system that can protect siRNA from degradation and facilitate their uptake across the cell membrane. In this study, the cationic lipid (GL67) was exploited, in addition to DC-Chol and DOPE lipids, to design an efficient liposomal nanocarrier for siRNA delivery. The physiochemical characterizations demonstrated that the molar ratio of 3:1 has proper particle size measurements from 144 nm to 332 nm and zeta potential of -9 mV to 47 mV that depends on the ratio of the GL67 in the liposomal formulation. Gel retardation assay exhibited that increasing the percentage of GL67 in the formulations has a good impact on the encapsulation efficiency compared to DC-Chol. The optimal formulations of the 3:1 M ratio also showed high metabolic activity against A549 cells following a 24 h cell exposure. Flow cytometry findings showed that the highest GL67 lipid ratio (100 % GL67 and 0 % DC-Chol) had the highest percentage of cellular uptake. The lipoplex nanocarriers based on GL67 lipid could potentially influence treating genetic diseases owing to the high internalization efficiency and safety profile.

Development of Imeglimin Electrospun Nanofibers as a Potential Buccal Antidiabetic Therapeutic Approach.

The prevalence of type 2 diabetes (T2D) has been growing worldwide; hence, safe and effective antidiabetics are critically warranted. Recently, imeglimin, a novel tetrahydrotriazene compound, has been approved for use in T2D patients in Japan. It has shown promising glucose-lowering properties by improving pancreatic beta-cell function and peripheral insulin sensitivity. Nevertheless, it has several drawbacks, including suboptimal oral absorption and gastrointestinal (GI) discomfort. Therefore, this study aimed to fabricate a novel formulation of imeglimin loaded into electrospun nanofibers to be delivered through the buccal cavity to overcome the current GI-related adverse events and to provide a convenient route of administration. The fabricated nanofibers were characterized for diameter, drug-loading (DL), disintegration, and drug release profiles. The data demonstrated that the imeglimin nanofibers had a diameter of 361 ± 54 nm and DL of 23.5 ± 0.2 µg/mg of fibers. The X-ray diffraction (XRD) data confirmed the solid dispersion of imeglimin, favoring drug solubility, and release with improved bioavailability. The rate of drug-loaded nanofibers disintegration was recorded at 2 ± 1 s, indicating the rapid disintegration ability of this dosage form and its suitability for buccal delivery, with a complete drug release after 30 min. The findings of this study suggest that the developed imeglimin nanofibers have the potential to be given via the buccal route, thereby achieving optimal therapeutic outcomes and improving patient compliance.