Direct Intracerebral Delivery of Carboplatin from PLGA Microspheres Against Experimental Malignant Glioma in Rats

Abstract

There has been an increasing interest in intracerebral delivery of anticancer agents using biodegradable polymers for the treatment of malignant glioma. This approach circumvents the blood-brain barrier (BBB) to achieve a high local drug concentration in the brain tumor sites and minimize side effects associated with a high systemic dose. It could also control local tumor recurrence and improve survival. In order to deliver anticancer drugs intracerebrally from polymers to tumor sites with minimal surgery, injectable poly(d,l-lactic-coglycolic acid) (PLGA) microspheres impregnated with carboplatin have been prepared. In the current studies, the brain tissue reaction to blank or carboplatin-loaded PLGA microspheres was investigated in rats. The PLGA micro-spheres were well tolerated by all of the rats. The brain tissue reaction to the blank microspheres was accompanied by mild edema, and macrophage/astrocyte/microglia proliferation. The tissue reaction to the carboplatin microspheres was characterized as edema, necrosis, and a more pronounced phagocytic inflammatory reaction. The observed inflammatory reactions decreased remarkably after 1 month. Carboplatin microspheres were then implanted intracerebrally in the rat glioma models. Higher drug concentrations were achieved in the brain tumor than in normal tissues. The survival and weight loss of the rats receiving carboplatin microspheres were compared with those of the rats receiving systemic doses. The local treatment was more effective in controlling the weight loss of the tumor-bearing rats, and was as effective as the systemic treatment in prolonging survival.

The brain tissue response to biodegradable poly(methylidene malonate 2.1.2)-based microspheres in the rat

“…In the case of 5-FU loaded particles, glial cells followed the same evolution pattern at least until day 8. These results are in accordance with previous publications concerning various drug carriers implanted in the striatum such as PLGA microspheres [15,[24][25][26], poly(e-caprolactone), ethylcellulose or polystyrene microspheres [27], poly[bis(p-carboxyphenoxy)propane] and sebacic acid implants [11][12][13][14]28] and 2-hydroxyethyl methacrylate copolymer microcapsules [29,30]. For all those controlled release systems, biodegradable or not, the brain tissue reaction after implantation consisted of a typical and mild foreign body reaction which resolved between 1 and 2 months.…”

Cell Culture and Animal Studies for Intracerebral Delivery of Borocaptate in Liposomal Formulation

“…Barth et al (1997) demonstrated that the route of administration, as well as disruption of the BBB, can enhance the uptake of BSH into tumor cells. Other intracerebral delivery studies also showed that implantation of drug-loaded dosage forms directly at the brain tumor site improved the ef cacy of the treatment (Olivi and Brem 1994;Chen et al 1998). Direct intracerebral injection of BSH-loaded liposomes may offer several advantages.…”

Preparation of self-solidifying polymeric depots from PLEC-PEG-PLEC triblock copolymers as an injectable drug delivery system

“…Second, heat and pressure are required to fabricate these depots in order to anneal and mold materials to a desired shape which may affect the stability of drugs especially gene, protein or hormone. Polymeric microspheres are also used as drug delivery systems for brain cancer chemotherapy [3,4]. However, fabrication of these particles is difficult to control size and porosity.…”