pH responsive PAIAm‐g‐PIPA microspheres: Preparation and drug release

Abstract

SYNOPSISPoly(N-isopropylacrylamide) (PIPA) was synthesized by radical polymerization with 2,2'-azobisisobutyronitrile (AIBN) as an initiator and 3-mercaptopropionic acid (MPA) as a chain-transfer reagent in methanol (MeOH) at 70°C for 7 h. The resultant PIPA was grafted to polyallylamine hydrochloride (PAlAm -HCl) by amide formation under the influence of water-soluble carbodiimide l-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC). The graft polymer was made into microspheres (MS) by chemical crosslinking. The pH-responsive drug release of the graft polymer microspheres was examined by releasing phenobarbital natrium (PN), which was carried on the microspheres by physical adsorption. A dynamic dialysis technique was used in the drug-release experiment and the drug-release-rate constants reflecting the drug release characteristic of polymer microspheres were obtained by constituting a mathematical model. The results indicated that the homopolymer PAlAm microspheres and the copolymer PAIAm-g-PIPA microspheres are both pH responsive to release P N and that in the neutral pH condition the release rate is the slowest. 0 1995 John Wiley & Sons, Inc. INTRODUCTIONThe external signal-responsive drug-delivery system has been paid more and more attention. The obvious advantage of this system is the "on-off" switching control release of a drug from a drug carrier by surrounding signals such as heat, chemical compounds, electric field, and pH. Many polymers such as polyacrylamide,' poly(N-acryloylpyrrolidine),2 poly(N-alkyl-substituted acrylamides)? and some liposomes4 can be used to achieve this "onoff'' drug-control release as a drug-carrier martrix. Among these polymers, poly(N-isopropylacrylamide)5 (PIPA) has demonstrated noticeable thermosensitivity in terms of water swelling. Okahata et a1.6 even used a large nylon capsule membrane with a surface-grafted poly(N-isopropylacrylamide) to regulate reversily the permeation of NaCl and dyes by ambient temperature change. Recently, Schild7 reported a detailed review of the specificity, synthesis, and application of PIPA. Changes in the swelling states of PIPA gels can influence the diffusion of solutes from within the gels to the outside aqueous media. The changes were mainly thermosensitive. However, the review reported also a novel e x t e n~i o n~'~ of the PIPA system in which acrylic acid as a comonomer was introduced consequently, the copolymer possessed not only a thermal response but also pH sensitivity. The lower critical solution temperature (LCST) shifts to higher temperature at higher pH due to repulsion between the ionized groups. Yan" also utilized PIPA to obtain controllable catalytic activity of the enzyme immobilized by the medium temperature. According to Yan's work, the phase transition of the graft copolymer polyallylamine hydrochloride (PAlAm) -g-PIPA was influenced not only by the temperature but also by the pH of the dissolution medium. Extensively, we carried out drug-release experiments with PAIAmg-PIPA as a drug carrier at various pH's....

Thermosensitive poly(allylamine)-g-poly(N-isopropylacrylamide): synthesis, phase separation and particle formation

“…Driven by this application and also others such as drug loading and release [34,35], we report here the synthesis of PAH-g-PNIPAAm obtained from the condensation between PAH and carboxylic end-capped PNIPAAm. The phase transition behavior and capability to form particles above the LCST were determined by dynamic light scattering, scanning force microscopy and transmission electron microscopy.…”

Robust Poly(allylamine)‐graft‐poly(N‐isopropylacrylamide) Particles Prepared by Physical Crosslinking with Poly(styrene sulfonate)

“…Researches show that graft copolymers can be made into robust microspheres by crosslinking. After loading a certain drug by physical adsorption, the microspheres exhibit a drug release property that is thermosensitive 11. For the PAH‐ g ‐PNIPAAm/PSS particles, the response of the particle volume to thermal stimuli has readily provided the capability for the particles to release loaded substance with temperature‐tunable behavior.…”

The relation between narrow-dispersed microcapsules and surfactants

“…Recently, core-shell microcapsules have been investigated widely for utilization in a controlled-release system, especially in drug delivery, where the polymeric wall has a permeable part with certain porosity that can determine the release behaviour of core materials. The many environmental stimuli-responsive microcapsules have been reported to act in response to changes in temperature (Chu et al 2001(Chu et al , 2002a, pH (Li et al 1995;Kidchob et al 1997;Kono et al 1999), light (Suzuki and Takenchi 1990), external electric field (Kwon et al 1991), magnetic field (Voigt et al 2001), ionic strength (Park et al 2000;Chu et al 2002b;Gao et al 2003) and so on. These 'smart' capsules continue to gather increasing attention.…”