Controlled delivery of taxol from poly(ethylene glycol)-coated poly(lactic acid) microspheres

Abstract

The development of injectable microspheres for sustained drug delivery to the arterial wall is a major challenge. We demonstrated the possibility of entrapping an antiproliferative agent, taxol, in poly(ethylene glycol) (PEG)-coated biodegradable poly(lactic acid) (PLA) microspheres with a mean diameter of 2-6 microm. A solution of taxol and PLA dissolved in an acetone/dichloromethane mixture was poured into an aqueous solution of PEG [or poly(vinyl alcohol) (PVA] with stirring with a high-speed homogenizer for the formation of microspheres. Taxol recovery in PLA-PEG microspheres was higher (61.2 +/- 2.3%) than with PVA-based (41.6 +/- 1.8%) preparations. An analysis by diffuse reflectance infrared Fourier transform spectroscopy revealed that PEG was incorporated well on the PLA microsphere surface. Scanning electron microscopy revealed that the PEG-coated PLA microspheres were spherical in shape and had a smooth surface texture like those of PVA-based preparations. The amount of drug release was much higher initially (25-30%); this was followed by a constant slow-release profile for a 30-day period of study. This PEG-coated PLA microsphere formulation may have potential for the targeted delivery of antiproliferative agents to treat restenosis.

Novel Biodegradable Polylactide/poly(ethylene glycol) Micelles Prepared by Direct Dissolution Method for Controlled Delivery of Anticancer Drugs

“…But serious side effects are associated with the use of Cremophor EL, including hypersensitivity reaction, nephrotoxicity, neurotoxicity and cardiotoxicity (9,10). Many novel delivery systems of paclitaxel have been investigated to reduce the side effects, such as parenteral emulsion (11), liposomes (12,13), nanoparticles (14)(15)(16)(17)(18)(19), micro-or nanospheres (20)(21)(22)(23)(24)(25), mixedmicelles (26), polymeric micelles (27)(28)(29)(30) and conjugates (31)(32)(33). The drug encapsulation abilities of these systems are affected by many parameters, such as polymer composition, drug feeding amount, fabrication method, etc.…”

Gelatin/chitosan/hyaluronan scaffold integrated with PLGA microspheres for cartilage tissue engineering

“…Microspheres are attracting increasing interest because of their diverse applications in the field of drug [16][17][18][19] and growth factor [20][21][22][23] delivery for tissue engineering. It has been reported that implantation of microspheres containing growth factors resulted in improved cell phenotype and chondrogenesis [24][25][26][27][28].…”

Effect of Particle Size of Nanospheres and Microspheres on the Cellular-Association and Cytotoxicity of Paclitaxel in 4T1 Cells

“…However, Cremophor EL is biologically and pharmaceutically active, causing anaphylactic hypersensitivity, hyperlipidemia, neurotoxicity, and in vitro cytotoxicity due to the formation of free radicals (9,10). In attempts to overcome the low aqueous solubility of paclitaxel as well as the undesirable toxicity of Cremophor EL, numerous alternate dosage forms have been investigated including gels (11), films (12), emulsions (13)(14)(15), liposomes (16)(17)(18), macromolecule conjugates (19), and particulate delivery systems (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32).…”

“…Nanospheres and microspheres containing paclitaxel have been investigated using various polymers such as polylactic-co-glycolic acid (PLGA) (21,(30)(31)(32)(33), poly-lactic acid (24,25), poly-ethylene oxide (25,26,31), poly-propylene oxide (27), and poly(-caprolactone) (20). The proposed advantages of particulate delivery systems for paclitaxel are that they 1) may avoid the use of toxic polyethoxylated castor oil, 2) may evade cellular efflux pumps, 3) can be administered orally or systemically, 4) inhibit tumor growth as well as prevent relapse after surgery, and 5) sustain the release of paclitaxel at therapeutic concentrations.…”

“…Hence, a faster and more complete release of paclitaxel is essential. To accelerate the release of paclitaxel, surfactants such as polyvinyl alcohol, vitamin E, and dipalmitoyl phosphatidylcholine have been added to reduce the surface tension and solubilize the hydrophobic drug (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(32)(33)(34)(35). Although, there has been significant progress in the development of particulate delivery systems containing paclitaxel, the effect of particle size of the nanospheres and microspheres preparation on the extent and mechanism of cell-association and cytotoxicity into the cancer cells has not been thoroughly investigated.…”