Abstract：
Intravesical instillation is an effective post-treatment for bladder cancer performed by delivering medications directly into the bladder to target the remaining cancer cells. The current study thus aimed to develop porous poly(L-lactide-co-ε-caprolactone) (PLCL) microspheres encapsulated with 10-hydroxycamptothecin (HCPT) via microfluidics to serve as a drug delivery system with persistent floating capacity and sustained HCPT-release property for intravesical instillation. A microfluidic device was designed to fabricate PLCL microspheres and encapsulate HCPT (HCPT-MS) within them; methanol and tridecane were introduced into an oil phase as a co-solvent and pore-forming agent, respectively, to regulate the floating ability of microspheres. The physicochemical properties of the resulting microspheres were characterized, and the floating behavior, release profile and anti-tumor effects of HCPT-MS were investigated. The obtained spherical HCPT-MS were 119.23 μm in size, monodisperse, and featured a porous concave surface and hollow structure. The encapsulation efficiency and drug loading of HCPT within HCPT-MS was around 67% and 4.9%, respectively. HCPT-MS exhibited impressive floating capabilities in water, PBS and artificial urine even in a simulated bladder dynamic environment. These microspheres remained afloat after being subjected to 90 repeated simulated urination processes. The sustained release of HCPT from these floating microspheres lasted for more than 10 days. The IC50 (half maximal inhibitory concentration) of HCPT-MS was calculated to be 52.14 μg mL-1. T24 cells (human bladder cancer cells) when cultured with HCPT-MS at such a concentration were severely inhibited, and the inhibition further enhanced with an increase in culture time. Hence, the feasibility of the current porous and floating HCPT-MS as a formulation for intravesical instillation to deliver medications into the bladder with sustained release and stability was thus substantiated.
摘要：
膀胱内滴注是通过将药物直接递送到膀胱中以靶向剩余的癌细胞而进行的膀胱癌的有效后处理。因此，当前的研究旨在通过微流体开发用10-羟基喜树碱（HCPT）封装的多孔聚（L-丙交酯-co-ε-己内酯）（PLCL）微球，以用作具有持久漂浮能力和持续HCPT释放性能的药物递送系统用于膀胱内滴注。设计了一种微流体装置来制造PLCL微球并将HCPT（HCPT-MS）封装在其中；将甲醇和十三烷作为共溶剂和成孔剂引入油相中，分别,调节微球的漂浮能力。对所得微球的理化性质进行了表征,和浮动行为，研究了HCPT-MS的释放曲线和抗肿瘤作用。所得球形HCPT-MS的大小为119.23μm,单分散,并具有多孔凹面和中空结构。HCPT-MS中HCPT的包封率和载药量分别为67%和4.9%左右,分别。HCPT-MS在水中表现出令人印象深刻的漂浮能力，PBS和人工尿液甚至在模拟膀胱动态环境中。这些微球在经历90次重复的模拟排尿过程后保持漂浮。从这些漂浮的微球中持续释放HCPT持续超过10天。计算HCPT-MS的IC50(半数最大抑制浓度)为52.14μgmL-1。T24细胞（人膀胱癌细胞）与HCPT-MS在这样的浓度下培养时受到严重抑制，随着培养时间的增加，抑制作用进一步增强。因此，因此,证实了目前的多孔和漂浮型HCPT-MS作为膀胱内滴注制剂将药物持续释放和稳定地递送至膀胱的可行性.
