pH Of Release Medium Research Articles

PH- and Calcium Ion-Dependent Release from Egg Phosphatidylcholine Liposomes Incorporating Hydrophobically Modified Alginate

Liposomes, which release their contents in response to change in environmental pH and Ca2+ concentration, were prepared by modifying the surface of egg phosphatidylcholine (EPC) liposome with hydrophobically modified alginate (Hm AL). The liposomes prepared using the ratio of 1:7 (Hm AL:EPC) was stable when the pH of release medium was higher than 6.5. They started to release at pH 6.0, and the degree of release in 300 sec was more than 80% at pH 4.5. The collapse of Hm AL chains, caused by the lack of intramolecular electrostatic repulsion, would impose a mechanical energy on the liposomal membrane, promoting a release from the liposomes. Liposomes bearing less amount of Hm AL exhibited less degree of release, but the release profiles were found similar whatever Hm AL to EPC ratio was. On the other hand, the liposomes bearing Hm AL released calcein significantly (10-30%) in 300 sec when Ca2+ was contained in the release medium (5 mM and 10 mM). The collapse or the gellation of Hm AL, caused by an electrostatic interaction between Ca2+ and the polysaccharide, would be responsible for the release.

Vanillin cross-linked chitosan microspheres for controlled release of resveratrol

In this work, resveratrol (Res) was incorporated into chitosan microspheres for controlled release and stabilisation. The microspheres were prepared by emulsion chemical cross-linking method, and vanillin was used as the novel cross-linker. The microspheres showed a smooth surface with irregular small particles and internal voids with a size distribution between 53 and 311 mu m. Interpenetrating network cross-linking mechanisms might account for the Schiff base reaction between chitosan and vanillin. The encapsulation efficiency of Res within microspheres was up to 93.68%. Res contained within microspheres was protected from light and heat compared with the free Res. In addition, release behaviours were governed by two distinct stages and dependent on pH of release media. Diffusion, swelling and erosion mechanisms might coexist for the full controlled release and Higuchi was the Most Suitable model for the whole release procedure, Thus, controlled release and stabilization of Res were achieved through incorporation of Res into cross-linked chitosan microspheres by vanillin. (C) 2009 Elsevier Ltd. All rights reserved.

Amphiphilic biodegradable poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) triblock copolymers: synthesis, characterization and their use as drug carriers for folic acid

Amphiphilic biodegradable poly(e-caprolactone)-poly(ethylene glycol)-poly (e-caprolactone) (PCEC) triblock copolymers have been successfully synthesized by the ring-opening polymerization of e-caprolactone (e-CL) employing SnOct as catalyst and double-hydroxyl capped PEG (DHPEG) as macro-initiator. The triblock structure and copolymer composition were conformed by FT-IR, 1H-NMR, and GPC. Using a membrane dialysis method, PCEC micelles were prepared with a core–shell type. The critical micelle concentration (CMC) of PCEC triblock copolymers was determined by fluorescence technique using pyrene as probe, and CMC values decreased with the increase of PCL chain length. From the observation of transmission electron microscopy (TEM), the morphology of polymer micelles was spherical in shape. Micelles size measured by dynamic light scattering (DLS) exhibited a narrow size distribution. Folic acid (FA) was then used as a model drug to incorporate into PCEC micelles. The diameter, drug loading, and drug release rate of PCEC micelles were influenced by the feed weight ratio of FA and copolymer, and polymer composition. In addition, in vitro release experiments of the drug-loaded PCEC micelles exhibited sustained release behavior without any burst effects and the release behavior was also affected by the pH of release media.

PH and ionic sensitive chitosan/carboxymethyl chitosan IPN complex films for the controlled release of coenzyme A

pH and ionic sensitive interpenetrating polymer network (IPN) complex films based on chitosan (CS) and carboxymethyl chitosan (CM-CS) were prepared by using glutaraldehyde as crosslinking agent. Its structure was characterized by FT-IR, which indicated that the IPN was formed. The films were studied by swelling, weight loss with time, and release of coenzyme A (CoA). It was found that the IPN films were sensitive to pH and ionic strength of the medium. The cumulative release rate of CoA decreased with CoA loading content, ionic strength or crosslinking agent increasing. The composition of the IPN films and pH of release medium also had significant effect on the release of CoA. The differences in the rates and amounts of released CoA may be attributed to the swelling behavior, the degradation of films, and interaction between drug molecule and polymer matrix. These results suggested CS/ CM-CS IPN films could be used as drug delivery carrier.

Drug release from xyloglucan beads coated with Eudragit for oral drug delivery

Xyloglucan (XG), which exhibits thermal sol to gel transition, non-toxicity, and low gelation concentration, is of interest in the development of sustained release carriers for drug delivery. Drug-loaded XG beads were prepared by extruding dropwise a dispersion of indomethacin in aqueous XG solution (2 wt.-%) through a syringe into corn oil. Enteric coating of XG bead was performed using Eudragit L 100 to improve the stability of XG bead in gastrointestinal (GI) track and to achieve gastroresistant drug release. Release behavior of indomethacin from XG beads in vitro was investigated as a function of loading content of drug, pH of release medium, and concentration of coating agent. Adhesive force of XG was also measured using the tensile test. Uniform-sized spherical beads with particle diameters ranging from 692 +/- 30 to 819 +/- 50 microm were obtained. The effect of drug content on the release of indomethacin from XG beads depended on the medium pH. Release of indomethacin from XG beads was retarded by coating with Eudragit and increased rapidly with the change in medium pH from 1.2 to 7.4. Adhesive force of XG was stronger than that of Carbopol 943 P, a well-known commercial mucoadhesive polymer, in wet state. Results indicate the enteric-coated XG beads may be suitable as a carrier for oral drug delivery of irritant drug in the stomach.

Release of albumin from chitosan-coated pectin beads in vitro

The release behavior of albumin from chitosan-coated pectin beads in vitro was investigated. The factors, such as concentration of CaCl 2, molecular weight of chitosan, pH of chitosan solution, and pH of release medium, which can have a significant effect on the release behavior from the beads, were discussed in this study. The loading efficiency (LE) of albumin showed maximum value when the concentration of CaCl 2 and the weight ratio of pectin to albumin were 2 wt.% and 2, respectively. The release of albumin from pectin beads could be retarded by coating with chitosan at various pH medium. The increase of the concentration of CaCl 2 induced the decrease of albumin release for uncoated-pectin beads, but not much difference of release for coated-pectin ones. The higher molecular weight of chitosan showed less albumin release than the lower one. The release of albumin from the chitosan-coated pectin beads was dependent on pH of coating solution and release medium, which might affect the degree of swelling of pectin beads.

Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure

By adopting a novel chitosan cross-linked method, i.e. chitosan/gelatin droplet coagulated at low temperature and then cross-linked by anions (sulfate, citrate and tripolyphosphate (TPP)), the chitosan beads were prepared. Scanning electron microscopy (SEM) observation showed that sulfate/chitosan and citrate/chitosan beads usually had a spherical shape, smooth surface morphology and integral inside structure. Cross-sectional analysis indicated that the cross-linking process of sulfate and citrate to chitosan was much faster than that of TPP due to their smaller molecular size. But, once completely cross-linked, TPP/chitosan beads possessed much better mechanical strength and the force to break the beads was approximately ten times higher than that of sulfate/chitosan or citrate/chitosan beads. Release media pH and ionic strength seriously influenced the controlled drug release properties of the beads, which related to the strength of electrostatic interaction between anions and chitosan. Sulfate and citrate cross-linked chitosan beads swelled and even dissociated in simulated gastric fluid (SGF) and hence, model drug (riboflavin) released completely in 5 h; while in simulated intestinal fluid (SIF), beads remained in a shrinkage state and drug released slowly (release % usually <70% in 24 h). However, swelling and drug release of TPP/chitosan bead was usually insensitive to media pH. Chitosan beads, cross-linked by a combination of TPP and citrate (or sulfate) together, not only had a good shape, but also improved pH-responsive drug release properties. Salt weakened the interaction of citrate, especially sulfate with chitosan and accelerated beads swelling and hence drug release rate, but it was insensitive to that of TPP/chitosan. These results indicate that ionically cross-linked chitosan beads may be useful in stomach specific drug delivery.

Development of a Sustained-Release Biodegradable Polymer Delivery System for Site-Specific Delivery of Oligonucleotides: Characterization of P(LA-GA) Copolymer Microspheres In Vitro

Antisense oligodeoxynucleotides (ODNs) can selectively inhibit individual gene expression provided they gain access to and remain stable at the target site for a sufficient period of time. Biodegradable sustained-release delivery systems may facilitate site-specific delivery and also prevent degradation of ODNs by nucleases whilst delivering the nucleic acid in a controlled manner to the desired site of action. In this study, we have characterized biodegradable poly (lactide-co-glycolide) (P(LA-GA)) 50:50 microspheres for the potential delivery of antisense oligonucleotides in vivo. Phosphodiester (PO) oligonucleotides complementary to either c-myc proto-oncogene or the tat gene in HIV-RNA were adequately incorporated within P(LA-GA) microspheres with entrapment efficiencies up to 60% depending on particles size. In vitro release profiles of antisense nucleic acids from 10-20 μm size microspheres over 56 days in physiological buffer were triphasic. Profiles were characterised by an initial burst effect during the first 48 hours (phase 1) of release followed by a more sustained release (phase 2) with an additional increased release (phase 3) being observed after 25 days which corresponded with bulk degradation of the copolymer matrix. The release profiles were influenced by microsphere size, copolymer molecular weight, ODN loading, ODN length and by the pH of release medium used. The serum stability of PO ODNs was significantly improved when entrapped within P(LA-GA) microspheres and the hybridization capability, as assessed by duplex melting (Tm) measurements, of released ODN was not impaired by the double-emulsion microsphere fabrication procedure used. Thus, P(LA-GA) microspheres appear to be promising candidates for improving site-specific delivery profiles for ODNs and are worthy of further evaluation in vivo.

PH-sensitive drug delivery system using [formula omitted] emulsion

A pH-sensitive drug delivery system has been prepared using an O W emulsion, which consists of a core and capsule. The core consists of oil and dispersed drug. A novel semi-interpenetrating networks (semi-IPNs) system has been developed to provide a capsule network which shows pH-sensitive swelling behavior. The first network consists of sodium alginate which disintegrates in the intestinal fluid. The other is a polyacrylic acid which provides pH-sensitive swelling capacity to the capsule network. The drug delivery system in this study showed a pH-sensitive drug release pattern which was due both to the diffusion of drug through the capsule network and to the escape of drug from the surface which underwent disintegration after swelling depending on the chemical composition of the capsule network and the pH of release media.

In vitro and in vivo evaluation of progesterone implants based on new biodegradable poly(glutamic and glutamate esters) copolymers.

New biodegradable polypeptidic copolymers of glutamic acid and tert-butyloxycarbonylmethyl glutamate were evaluated as implantable drug delivery systems. Three copolymers varying in degrees of esterification, which is inversely proportional to the number of glutamic residues, were selected for their range of hydrophilicity and biodegradation rates. Progesterone-containing implants were then prepared by means of an extrusion process and both in vitro and in vivo evaluations were performed. The effects of drug loading, nature, and pH of release medium were investigated. In vitro/in vivo correlations were established for some types of implants. Finally, mathematical fitting of the data, using published models, helped to better understand the mechanisms governing release.