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

Abstract

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.

Keywords: Arabin pessaries; Electrospinning; Nanofibers; Preterm labor; Progesterone; Vaginal delivery.

Graphical abstract

Fig. 1

The chemical structure of progesterone drawn by ACD/ChemSketch.

Fig. 2

SEM images of that (A) blank nanofibers and (B) progesterone-loaded nanofibers as smooth, non-porous, and non-beaded, with average diameters of, (C) blank nanofibers diameter distribution and (D) progesterone-loaded nanofibers diameter distribution. The diameter of the blank and progesterone-loaded nanofibrous systems were measured as 282 ± 55 nm and 397 ± 88 nm, respectively (n = 30).

Fig. 3

XRD Bragg reflection patterns of progesterone and PCL, their PM, and the blank and progesterone-loaded nanofibrous systems. The patterns showed that progesterone was in the crystalline form as a pure drug and the PM, while the characteristic reflections of progesterone disappeared in the drug-loaded nanofibers due to its molecular dispersion. DL: drug-loaded, PM: physical mixture.

Fig. 4

FTIR transmissions of progesterone and PCL, their PM, and the blank and progesterone-loaded nanofibers. The spectra showed that the function groups presented in the progesterone and PCL also presented in the drug-loaded nanofibers, with a slight shift, but lacked in the blank nanofibers. PM: physical mixture, DL: drug-loaded.

Fig. 5

The developed HPLC calibration curve of progesterone showed an excellent linearity (R² = 0.9999).

Fig. 6

Progesterone-loaded nanofibers release profile. The result shows a sustained release profile for progesterone released after 90 days is presented as the mean ± SD (n = 3).

Fig. 7

SEM images showing the morphology of the progesterone-loaded fibers (A) before the release, and (B) 6 days after the release in PBS.

Fig. 8

Cell viability of progesterone upon 24, 48 and 72-hours treatment of the human skin fibroblast cells (HFF-1). The figure revealed that progesterone is not toxic at ≤ 32 µg/mL upon 24 and 48-hour exposure and ≤ 8 µg/mL upon exposure for 72-hour. Results are plotted as mean ± SD (n = 3).