In Vitro and In Vivo Drug Release from a Nano-Hydroxyapatite Reinforced Resorbable Nanofibrous Scaffold for Treating Female Pelvic Organ Prolapse

Pelvic prolapse stands as a substantial medical concern, notably impacting a significant segment of the population, predominantly women. This condition, characterized by the descent of pelvic organs, such as the uterus, bladder, or rectum, from their normal positions, can lead to a range of distressing symptoms, including pelvic pressure, urinary incontinence, and discomfort during intercourse. Clinical challenges abound in the treatment landscape of pelvic prolapse, stemming from its multifactorial etiology and the diverse array of symptoms experienced by affected individuals. Current treatment options, while offering relief to some extent, often fall short in addressing the full spectrum of symptoms and may pose risks of complications or recurrence. Consequently, there exists a palpable need for innovative solutions that can provide more effective, durable, and patient-tailored interventions for pelvic prolapse. We manufactured an integrated polycaprolactone (PCL) mesh, reinforced with nano-hydroxyapatite (nHA), along with drug-eluting poly(lactic-co-glycolic acid) (PLGA) nanofibers for a prolapse scaffold. This aims to offer a promising avenue for enhanced treatment outcomes and improved quality of life for individuals grappling with pelvic prolapse. Solution extrusion additive manufacturing and electrospinning methods were utilized to prepare the nHA filled PCL mesh and drug-incorporated PLGA nanofibers, respectively. The pharmaceuticals employed included metronidazole, ketorolac, bleomycin, and estrone. Properties of fabricated resorbable scaffolds were assessed. The in vitro release characteristics of various pharmaceuticals from the meshes/nanofibers were evaluated. Furthermore, the in vivo drug elution pattern was also estimated on a rat model. The empirical data show that nHA reinforced PCL mesh exhibited superior mechanical strength to virgin PCL mesh. Electrospun resorbable nanofibers possessed diameters ranging from 85 to 540 nm, and released effective metronidazole, ketorolac, bleomycin, and estradiol, respectively, for 9, 30, 3, and over 30 days in vitro. Further, the mesh/nanofiber scaffolds also liberated high drug levels at the target site for more than 28 days in vivo, while the drug concentrations in blood remained low. This discovery suggests that resorbable scaffold can serve as a viable option for treating female pelvic organ prolapse.