Biodegradable polymeric microspheres and nanospheres for drug delivery in the peritoneum

Abstract

Drug delivery to the peritoneum is hampered by rapid clearance, and could be improved by application of controlled release technology. We investigated the suitability for peritoneal use of micro- and nanoparticles of poly(lactic-co-glycolic) acid (PLGA), a biodegradable polymer with generally excellent biocompatibility commonly used for controlled drug release. We injected 90 kDa PLGA microparticles, 5-250 microm in diameter, into the murine peritoneum, in dosages of 10-100 mg (n=3-5 per group). We found a high incidence of polymeric residue and adhesions 2 weeks after injection (e.g., 50 mg of 5-microm microparticles caused adhesions in 83% of animals). Histology revealed chronic inflammation, with foreign body giant cells prominent with particles>5 microm in diameter. Five micrometer microspheres made from 54, 57, and 10 kDa PLGA (gamma irradiated) caused fewer adhesions (16.7%) with a similar incidence of residue. Nanoparticles (265 nm) of 90 kDa PLGA also caused much fewer adhesions (6.3% of animals), possibly because they were cleared from the peritoneum within 2 days, and sequestered in the spleen and liver, where foamy macrophages were noted. The effect of sterilization technique on the incidence of adhesion formation is also studied.

Microparticles and nanoparticles for drug delivery

“…Microparticles 5, 25, 60, and 250 mm in diameter injected into the peritoneum of mice remained there for at least two week. In contrast, an equal mass of nanoparticles of the same material showed almost complete clearance from the peritoneum in the same time frame (Kohane et al, 2006). The spleens of those mice were enlarged and discolored and on light microscopy revealed numerous macrophages with a foamy appearance due to the accumulation of a large amount of polymeric material.…”

“…In cases where nanoparticles have a tendency to leave a locale where they wish to be maintained, they can be prevented from doing so. One example is in the use of hydrogels to keep polymeric nanoparticles in the peritoneum (Yeo et al, 2006b), which would otherwise leave for the reticuloendothelial system, particularly the spleen (Kohane et al, 2006).…”

NanoCipro encapsulation in monodisperse large porous PLGA microparticles

“…Polymer chemistry and control over the particle size distribution through emulsification-type processes have been used, along with other factors, to control the release rate of the drug from the particles [5]. Much effort has been expended in predicting the loading and release of various drugs from polymeric microparticles [4].…”

Nanomedicine-based intraperitoneal therapy for the treatment of peritoneal carcinomatosis — Mission possible?

“…Langer and coworkers evaluated 265 nm PLGA NPs of 90 kDa as strategy to prolong drug delivery in the murine peritoneum and compared the biodistribution with 5-250 µm sized PLGA microparticles (MPs) [61]. All NPs were cleared from the peritoneum within 2 days after administration, and accumulated in the mononuclear phagocyte system (MPS) organs, namely the liver and spleen.…”

“…All NPs were cleared from the peritoneum within 2 days after administration, and accumulated in the mononuclear phagocyte system (MPS) organs, namely the liver and spleen. MPs were retained in the peritoneal cavity for a longer time period, but a high incidence of adhesions 2 weeks after injection of the MPs made them unsuitable for long term delivery to the peritoneum [61]. Similarly, Tsai et al examined the effect of carrier size on the disposition and anti-tumor activity of paclitaxel (PTX) [62].…”