Semen-sensitive PCL/PLGA/HA-based layered electrospun scaffolds containing levonorgestrel (LNG) for intravaginal...

The development of electrospun scaffolds for use in contraception has been of great importance considering the associated adverse and dose-related side effects observed with existing contraception methods. These include the presence of irregular bleeding, amenorrhea, nausea, breast tenderness, increased risks of ovarian and endometrial cancer etc. This research aims at developing electrospun nanofibrous scaffolds for vaginal delivery using polycaprolactone (PCL), poly (lactic-co-glycolic acid) (PLGA) and hyaluronic Acid (HA) loaded with levonorgestrel (LNG). The electrospun scaffold will facilitate the triggered release of low dose LNG via interaction with seminal fluid. The high degradability of the nanofibers will improve clearance, eliminate related side effects, and speed up the time to return to fertility. Electrospun scaffolds were prepared by far-field electrospinning using a plate and wire collector with a voltage range of 25-30 KV and a flow rate of 1 mL/h. Fibers obtained were subjected to morphological, chemical, thermal and mechanical characterization while in vitro mucoadhesion, in vitro degradation and safety assessment studies in a rabbit model were also carried out. Scanning electron microscopy displayed uniformed, closely packed nanofibers. The differential scanning calorimetry analysis indicated that LNG was distributed throughout the electrospun scaffolds without interacting with the polymer matrix. Fourier transform infrared and x-ray diffraction evaluations revealed no drug-polymer interaction in LNG-loaded fibers. Fibers exhibited adequate tensile strength and mucoadhesion. Degradation was observed to be highest in the combination of SVF (Simulated Vaginal Fluid)/SF (Seminal Fluid) compared to SVF alone; due to the presence of hyaluronidase in the seminal fluid which breaks down the polymer matrix to facilitate drug release. The release pattern followed Higuchi kinetics for both SVF and SVF/SF. About 68 % of the drug was released in 5 mins when there was contact with seminal fluid while in 72 h about 48 % of LNG was released from fiber matrix in SVF alone. These electrospun scaffolds for intravaginal delivery of LNG present as an innovative tool for hormonal contraception through the controlled release of low-dose LNG from a polymer matrix in the presence of SF.