Mitigating gastrointestinal side effects of risedronate sodium: A study on Bletilla striata polysaccharide...

Risedronate sodium (RIS) is a primary treatment for postmenopausal osteoporosis, but oral administration requires patients to remain upright to prevent side effects like esophagitis, gastritis, and ulcers, which can be difficult for those with fatigue or bone pain. This study developed RIS-loaded Bletilla striata polysaccharide microneedles (RIS-BMNs) with sufficient mechanical strength for effective skin penetration and drug delivery. Franz diffusion cell experiments showed that RIS-BMNs achieved 3 times higher in vitro transdermal absorption than the RIS solution and 2.6 times more than RIS patches. The stimulation test found that RIS-BMNs caused minimal skin irritation, which resolved within 12 h. RIS-BMNs also promoted cell proliferation and wound healing, as shown by in vitro cell viability and migration tests, and improved bone trabeculae and density in osteoporotic rats, according to micro-CT imaging and H&E staining. Biochemical markers (BGP, IL-6, CTX-I, TRAP, OPG, and PINP) indicated that RIS-BMNs had anti-osteoporotic effects comparable to oral RIS but without gastrointestinal side effects, as confirmed by H&E staining. Our new transdermal method for RIS could improve adherence in treating postmenopausal osteoporosis.