Poly a-cyanoacrylate

One of the most striking differences between protein-dominated substrates e,g., skin, tissue masses, and blood) and other solid, semi-solid, or liquid surfaces is in their wettability and adhesiveness with other materials. Work on the development of surgical adhesives based upon the poly(a-cyanoacrylates) used successfully in hemostasis for massive... 

Figure 4c illustrates interfacial polymerisation encapsulation processes in which the reactant(s) that polymerise to form the capsule shell is transported exclusively from the continuous phase of the system to the dispersed phase—continuous phase interface where polymerisation occurs and a capsule shell is produced. This type of encapsulation process has been carried out at Hquid—Hquid and soHd—Hquid interfaces. An example of the Hquid—Hquid case is the spontaneous polymerisation reaction of cyanoacrylate monomers at the water—solvent interface formed by dispersing water in a continuous solvent phase (14). The poly(alkyl cyanoacrylate) produced by this spontaneous reaction encapsulates the dispersed water droplets. An example of the soHd—Hquid process is where a core material is dispersed in aqueous media that contains a water-immiscible surfactant along with a controUed amount of surfactant. A water-immiscible monomer that polymerises by free-radical polymerisation is added to the system and free-radical polymerisation localised at the core material—aqueous phase interface is initiated thereby generating a capsule sheU (15). 

In order to become useful dmg delivery devices, biodegradable polymers must be formable into desired shapes of appropriate size, have adequate dimensional stability and appropriate strength-loss characteristics, be completely biodegradable, and be sterilizahle (70). The polymers most often studied for biodegradable dmg delivery applications are carboxylic acid derivatives such as polyamides poly(a-hydroxy acids) such as poly(lactic acid) [26100-51-6] and poly(glycolic acid) [26124-68-5], cross-linked polyesters poly(orthoesters) poly anhydrides and poly(alkyl 2-cyanoacrylates). The relative stabiUty of hydrolytically labile linkages ia these polymers (70) is as follows ... 

Prolonged hypoglycemic effect of insulin was reported after using poly(butyl cyanoacrylate) microparticles with a mean diameter of 254.7 nm (Zhang et al. 2001). Insulin-loaded poly(butyl cyanoacrylate) microparticles were prepared by emulsion polymerization in the presence of insulin. Insulin-loaded microparticles were administered intratracheally to normal rats. The duration of glucose levels below 80% of baseline was maintained for a longer period when insulin was administered in... 

An alternative hydrophobic microparticulate dosage form can be produced using poly(alkyl cyanoacrylates) also referred to as simply poly(cyanoacrylates) (PCAs) (Table 11.3). Poly(cyanoacrylates) are a class of addition polymers that undergo polymerization under mild conditions, and even upon the addition of water or ethanol. Poly(cyanoacrylates) have been widely investigated for delivery of biomacromolecules. Due to their properties, cyanoacrylates can easily be formed into two types of particles spheres (Couvreur et al. 1982) or capsules (Al-Khouri Fallouh et al. 1986), both of which can be used to deliver biomacromolecules. The most used of the poly(cyanoacrylates) is poly (isobutyl cyanoacrylate) (PBCA). The reason... 

PBCA has been extensively investigated is that it can easily be formed into microparticles with the aid of ethanol as a solubilizer. Other PCAs tend to polymerize in the presence of ethanol, including poly(isohexyl cyanoacrylate) (PIHC A) (Chouinard et al. 1991). 

POLY (ETHYL a - CYANOACRYLATE -CO-ETHYL a -CARBOXAMIDO ACRYLATE) (9 1) (FMR-E101 (FUJI CHEMICAL)) CN CONH- I I CH c-CH.-C-2 I I COOC2H5 COOC2H5 2 X 1 05 1.5 54... 

Qaddoumi et al. [65] studied the uptake of PLGA nanoparticles in rabbit conjunctival epithelial cell culture. The highest uptake by cultured conjunctival cells was achieved for the smallest particles (100 nm), compared to larger 800 nm and 10 pm particles. A study of the fate of the tiny 100-nm particles following 2 h of cultured cells exposure to a 0.5 mg/mL dose showed that 6% was internalized by conjunctival epithelial cells, 1.5% was surface-bound, whereas the remainder of the dose was found in the donor medium. In an in vivo rabbit eye study [66] on the uptake of poly(hexyl cyanoacrylate) nanoparticles, 6 h postinstillation into the conjunctival sac, it was found that the fraction that was internalized by conjunctival epithelial cells was only 1% of the dose reflecting in vivo precorneal elimination... 

Vezin, W., and Florence, A. In vitro heterogeneous degradation of poly(re-alkyl a-cyanoacrylates). J. Biomed. Mater. Res. 14 93—106, 1980. 

Poly(alkyl cyanoacrylate) nanoparticles accumulate in the liver (60-90% of the injected dose) and the spleen upon iv injection, with the macrophages in the liver being their major target. Nanoparticles loaded with doxorubicin have shown a markedly enhanced therapeutic index in a number of animal tumor models. 

Aboubakar et al. [47] studied the physico-chemical characterization of insulin-loaded poly(isobutyl cyanoacrylate) nanocapsules obtained by interfacial polymerization. They claimed that the large amount of ethanol used in the preparation of the nanocapsules initiated the polymerization of isobutyl cyanoacrylate and preserved the peptide from a reaction with monomer, resulting in a high encapsulation rate of insulin. From their investigations, it appears that insulin was located inside the core of the nanocapsules and not simply adsorbed onto their surface. 

Poly(alkyl-cyanoacrylates) As poly(alkyl-cyanoacrylates) form strong bonds with polar substrates including the skin and living tissues, they exhibit bioadhesive properties. These polymers are synthesized by free-radical, anionic, or zwitterionic polymerization. As detailed in a recent review, poly(alkyl-cyanoacrylate) nanoparticles are prepared by emulsion polymerization, interfacial polymerization, nanoprecipitation, and emulsion-solvent evaporation methods [102],... 

Nanoparticles of synthetic polymers are usually manufactured by dispersion of preformed polymers. Although many methods can be used, they may be classified as monomer polymerization, nanoprecipitation, emulsion diffusion/solvent evaporation, and salting out. An appropriate method is selected mainly depending on polymer and drug natures. Polymerization of polymer monomers has been developed usually using poly(alkyl cyanoacrylate) [96,97]. Organic solvents are usually used in polymerization. A detailed description of this method is not provided here. 

Bootz, A., et al. (2004), Comparison of scanning electron microscopy, dynamic light scattering and analytical ultracentrifugation for the sizing of poly(butyl cyanoacrylate) nanoparticles, Eur. J. Pharm. Biopharm., 57(2), 369-375. 

The next three polymers in this series are aU ethyl acrylates, meaning that while the backbone (a) substituent is different in all three structures, the ester side-chain group (P) is the same for aU of them ( CH2CH3). Polymer 3 is poly(ethyl methacrylate) (PEMA), and 4 is poly(ethyl cyanoacrylate) (PECA), which may be recognizable as a primary component of the so-called superglues. Polymer 5 is poly(ethyl acrylate) (PEA), with H on the backbone a-position. Erom structure 3 to 4 to 5, the a-substituent becomes simpler in structure and this will be reflected in the observed TREPR spectra below in terms of the number of observed transitions, and in some cases the linewidths as well. 

Peracchia, M.T. Desmaele, D. Couvreur, P. D Angelo, J. Synthesis of a novel poly(PEG-cyanoacrylate-co-alkylcya-noacrylate) amphiphilic copolymer for the development of stealth PEG-coated nanoparticles. Macromolecules 1997, 30, 846-851. 

Damge, C. Vonderscher, J. Marbach, P. Pinget, M. Poly(alkyl cyanoacrylate) nanocapsules as a delivery system in the rat for octreotide, a long-acting somatostatin analogue. J. Pharm. Pharmacol. 1997, 49, 949-954. 

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