Abstract
Polyalkylcyanoacrylate (PACA) is a biodegradable and biocompatible material and PACA nanoparticles prepared via emulsion are capable of encapsulating various kinds of drugs and are eminently suitable as anti-tumor drug delivery carrier for treatment of cancer since it’s characteristic of rapid degradation rate. The type used in application and study is homopolymer, fast and uncontrollable degradation rate limit PACA as drug carrier applied for long-term release and met the required drug release rate on various clinical treatments. Compared with other commonly used materials, excessively fast degradation rate of PACA causes the higher cytotoxicity arising from the high concentration of degradation products. Hence, the first part of this research, core-shell type of nanoparticles with manipulated degradation rate and balanced hydrophilic/hydrophobic properties were designed and characterized. The nanoparticles based on the copolymers of n-butyl cyanoacrylate (BCA) and 2-octyl cyanoacrylate (OCA) were prepared by anion emulsion polymerization in 0.01 N HCl solution with pluronic F127 as the stabilizer. These nanoparticles were spherical in shape and with size smaller than 100 nm in a narrow distribution. The particle size, zeta potential, molecular weight, hydrophobicity and degradation rate of the copolymer depended on its composition significantly. In vitro chemical hydrolytic studies indicated that the degradation rate of the NPs could be controlled over 200-fold by adjusting the BCA/OCA ratio. Differential scanning calorimetry measurements verified the existence of copolymer with tapered structure which was induced by the reactivity difference of the monomers. A BCA/OCA core-shell structure is postulated that the OCA rich segments were mainly located in the core of the NPs. The cytotoxicity of poly(2-octyl cyanoactylate) (POCA) is quite lower than that of poly(n-butyl cyanoacrylate) (PBCA) and the toxicity of poly(BCA-co-OCA) nanoparticles is similar to that of PBCA nanoparticles. The most common approach of preparing drug-loaded PACA nanoparticles is either incorporation during the process of emulsion polymerization or adsorption by the surface of formed nanoparticles. The maximum weight of encapsulated drug is limited to the drug solubility in medium. It is expected that drug-loaded PACA nanoparticles with low drug loading efficiency for hydrophobic drugs such as the most representative drug of paclitaxel. The second part of this study, the strategy of miniemulsion polymerization is successful to obtain stable paclitaxel-loaded PBCA nanoparticles containing high loading and encapsulation efficiency simultaneously were achieved in the presence of pluronic F127. It was found that both drug loading and encapsulation efficiencies of PBCA nanoparticles prepared by miniemulsion were higher (approximately 3 times) than those obtained by emulsion with similar paclitaxel content in the feed monomer (1 % (w/w)). Furthermore, the loading and encapsulation efficiencies increased concurrently (to a maximum of 4 % and 80 % respectively) with increasing paclitaxel content and these nanoparticles were spherical in shape and with size near 100 nm. XRD patterns revealed that paclitaxel in particles was distributed in the molecular or amorphous state or in the form of small crystals. The in vitro drug release profile of drug-loaded PBCA nanoparticles prepared from miniemulsion exhibited a gradual release; more than 80 % (w/w) of the paclitaxl was released after 96 hours. Thus, miniemulsion polymerization could be used as a successful strategy to effectively encapsulate highly hydrophobic drugs in the PACA nanoparticles.