The effect of microsphere degradation rate on the efficacy of polymeric microspheres as bulking agents: An 18‐month follow‐up study

Abstract

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(lacticco-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.

The effect and safety of polylactic acid and adipose‐derived stromal vascular fraction cell as an injectable bulking agent in urologic field: A 24‐week follow‐up study

“…The volume reduction became slowed to the point where 65-70% of the injection volume was maintained at 24 weeks. This finding is consistent with the results of Kang et al 18 The formation of collagen and muscle tissues became evident in microspheres between 8 and 16 weeks and proliferation of new tissue was also observed. This study therefore confirms the potential of PLA as bulking agents in management of urological disease.…”

“…As hydrophobicity is greater in PLA than PLGA, the duration of hydrolysis increases in PLA. [16][17][18] PLA have been explored for clinical objectives over the last four decades. [19][20][21][22] Injectable PLA has been used as a cosmetic volume enhancer since 1999.…”

“…Kang et al 18 reported that the volume of implanted PLA in dorsum of mice slowly decreased to 52% of initial volume at 12 months and maintained that volume until 18 months. Differing from our study, however, they didn't investigate the effect of SVF cells and safety of PLA.…”

Liraglutide-loaded poly(lactic-co-glycolic acid) microspheres: Preparation and in vivo evaluation

“…The results obtained from HE staining verify that the liraglutide-loaded PLGA microspheres are safe and non-toxic, as previously found by Kang et al (2007).…”

Design of Protein‐Releasing Chitosan Channels

“…48 PLGA microsphere systems have been shown to be capable of degradation over timescales of a few weeks 46,49 to several months. 50,51 Protein stability is always one of the biggest concerns in drug delivery systems. As shown in Figure 4B, the majority of alkaline phosphatase remained bioactive throughout the study.…”