The effect of microsphere degradation rate on the efficacy of polymeric microspheres as bulking agents: an 18-month follow-up study.
The injection of bulking substances has been proposed as a new therapy to treat urinary incontinence and vesicoureteral reflux. Our previous study demonstrated that poly(lactic-co-glycolic acid) (PLGA) microspheres have the potential to serve as a bulking agent for urological injection therapies. Hybrid tissues exhibiting a bulking effect were formed in vivo by PLGA microsphere injection, but long-term volume stability was not proven. In this study, we hypothesized that the biodegradation rate of the bulking substance (polymer microspheres) would affect the duration of volume conservation of the induced hybrid tissue. To test this hypothesis, rapidly degrading 75:25 PLGA microspheres and slowly degrading poly(L-lactic acid) (PLLA) microspheres were used as injectable bulking agents for the injection therapy. In vitro degradation tests showed that the mass losses of PLLA and PLGA were 16 and 96% of the initial masses, respectively, at 30 weeks. PLLA and PLGA microspheres were injected into the subcutaneous dorsum of mice. Both types of microspheres were easily injectable through 24-gauge needles. Histological examinations at various time points indicated that host cells from the surrounding tissues migrated to the spaces between both types of injected microspheres and formed new hybrid tissue structures. Lymphocyte migration was noted around the implanted PLGA and PLLA microspheres, but the inflammatory reaction diminished with time. Importantly, the volume of the PLLA hybrid tissues slowly decreased to 52% of the initial volume at 12 months and maintained that volume until 18 months, whereas the volume of the PLGA hybrid tissues rapidly decreased to 22% at 6 months, and the PLGA hybrid tissues disappeared at 11 months. These results show that the biodegradation rate of the bulking substance may be useful for controlling the duration of volume conservation of the induced hybrid tissue.
Kang
Sun-Woong
SW
Department of Chemical Engineering, Hanyang University, Seoul 133-791, South Korea.
Cho
Eui Ri
ER
Jeon
Oju
O
Kim
Byung-Soo
BS
D000818:Animals; D002465:Cell Movement; D005549:Foreign-Body Reaction / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D019344:Lactic Acid / Q000737:chemistry; D008214:Lymphocytes / Q000473:pathology; D008422:Materials Testing; D051379:Mice; D008813:Mice, Inbred ICR; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D013997:Time Factors
D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid