Release Of Dextran Research Articles

Multimodal delivery of irinotecan from microparticles with two distinct compartments

In the last several decades, research in the field of drug delivery has been challenged with the fabrication of carrier systems engineered to deliver therapeutics to the target site with sustained and controlled release kinetics. Herein, we report the fabrication of microparticles composed of two distinct compartments: i) one compartment containing a pH responsive polymer, acetal-modified dextran, and PLGA (polylactide-co-glycolide), and ii) one compartment composed entirely of PLGA. We demonstrate the complete release of dextran from the microparticles during a 10-hour period in an acidic pH environment and the complete degradation of one compartment in less than 24h. This is in congruence with the stability of the same microparticles in neutral pH over the 24-hour period. Such microparticles can be used as pH responsive carrier systems for drug delivery applications where their cargo will only be released when the optimum pH window is reached. The feasibility of the microparticle system for such an application was confirmed by encapsulating a cancer therapeutic, irinotecan, in the compartment containing the acetal-modified dextran polymer and the pH dependent release over a 5-day period was studied. It was found that upon pH change to an acidic environment, over 50% of the drug was first released at a rapid rate for 10h, similar to that observed for the dextran release, before continuing at a more controlled rate for 4days. As such, these microparticles can play an important role in the fabrication of novel drug delivery systems due to the selective, controlled, and pH responsive release of their encapsulated therapeutics.

Materials characterization of the low temperature sensitive liposome (LTSL): effects of the lipid composition (lysolipid and DSPE–PEG2000) on the thermal transition and release of doxorubicin

This paper describes how we have used material science, physical chemistry, and some luck, to design a new thermal-sensitive liposome (the low temperature sensitive liposome (LTSL)) that responds at clinically attainable hyperthermic temperatures releasing its drug in a matter of seconds as it passes through the microvasculature of a warmed tumor. The LTSL is composed of a judicial combination of three component lipids, each with a specific function and each affecting specific material properties, including a sharp thermal transition and a rapid on-set of membrane permeability to small ions, drugs and small dextran polymers. Experimentally, the paper describes how bilayer-concentration changes involving the lysolipid and the presence or absence of DSPE-PEG2000 affect both the lipid transition temperature and the drug release. While the inclusion of 4 mol% DSPE-PEG2000 raises the transition temperature peak (T(m)) by about 1 degrees C, the inclusion of 5.0, 9.7, 12.7 and 18.0 mol% MSPC slightly lowered this peak back to 41.7 degrees C, while not further broadening the peak breadth. As for drug release, in the absence of MSPC, the encapsulated doxorubicin-citrate is hardly released at all. Increasing the composition of MSPC in the lipid mixture (5.0, 7.4, 8.5 and 9.3 mol% MSPC) shows faster and faster initial doxorubicin release rates, with 8.5 and 9.3 mol% MSPC formulations giving 80% of encapsulated drug released in 4 and 3 min, respectively. The Thermodox formulation (9.7 mol% MSPC) gives 60% released in the first 20 s. The presence of PEG-lipid is found to be essential in order for the lysolipid-induced permeability to reach these very fast times. From drug and dextran release experiments, and estimates of the molecular and pore size, the conclusions are that: in order to induce lasting nanopores in lipid bilayers -10 nm diameter, they initially require the presence (from the solid phase structure) of grain boundary defects at the DPPC transition and the permeabilizing component(s) can either be a pore forming lysolipid/surfactant plus a PEG-lipid, or can be generated by a PEG-surfactant incorporated at -4-5 mol%. The final discussion is centered around the postulated defect structures that result in membrane leakage and the permeability of doxorubicin and H+ ions.

Temperature-responsive electrospun nanofibers for ‘on–off’ switchable release of dextran

We propose a new type of ‘smart’ nanofiber (NF) with dynamically and reversibly tunable properties for the ‘on–off’ controlled release of the polysaccharide dextran. The fibers are produced by electrospinning copolymers of N-isopropylacrylamide (NIPAAm) and N-hydroxymethylacrylamide (HMAAm). The OH groups of HMAAm are subsequently crosslinked by thermal curing. The copolymers were successfully fabricated into a well-defined nanofibrous structure with a diameter of about 600–700 nm, and the fibers preserved their morphology even after thermal curing. The resulting crosslinked NFs showed rapid and reversible volume changes in aqueous media in response to cycles of temperature alternation. The fibrous morphology was maintained for the crosslinked NFs even after the cycles of temperature alternation, while non-crosslinked NFs collapsed and dispersed quickly in the aqueous solution. Dextran-containing NFs were prepared by electrospinning the copolymers blended with fluorescein isothiocyanate (FITC)-dextran, and the ‘on–off’ switchable release of FITC-dextran from the crosslinked NFs was observed. Almost all the FITC-dextran was released from the NFs after six heating cycles, whereas only a negligible amount of FITC-dextran was evolved during the cooling process. The reported incorporation of smart properties into NFs takes advantage of their extremely large surface area and porosity and is expected to provide a simple platform for on–off drug delivery.

Design of core–shell gel beads for time‐programmed protein release

Calcium alginate gel beads were coated with calcium poly(γ-glutamate) (Ca-γ-PGA) or its alkylate to modulate a release onset time of macromolecular drugs like proteins. Dextran release from coated alginate gel beads with γ-PGA increased the onset release time from 13 min for bare alginate beads to 49 min for γ-PGA-coated alginate gel beads with diameters of about 0.6 mm. The γ-PGA coating may act as a barrier to disintegration due to the swelling of alginate gels through ion exchange of Ca(2+) with Na(+) . As the osmotic pressure increases inside the γ-PGA capsule, the γ-PGA layer eventually delaminates to form flakes and enables drug release. To further increase the onset release time, we modified the carboxyl groups of γ-PGA with 1-bromobutane to increase the hydrophobicity of the coating layers. By incorporating 20 mol % butyl groups, the onset release time increased to 87 min. Even for proteins, the hydrophobic polymer coating of the gels was effective at increasing the lag time. Similar to the release of dextran, proteins, albumin (bovine serum albumin), immunoglobulin G, and fibrinogen showed an S-shaped release curve with onset release time, in which the onset release time depends on the molecular weight and their conformation. In conclusion, we successfully prepared modified alginate gel beads with injectable bead diameters and modulated the onset release time of macromolecular drugs.

Drug Release from a pH-Sensitive Multiblock Co-Polymer Thermogel

A Pluronic®-based pH-sensitive multiblock co-polymer thermogel has been proposed for sustained release of therapeutic agents. Hydrophobic small-molecule drugs (paclitaxel and camptothecin) and model hy-drophilic macromolecules (fluorescein-labeled dextrans of molecular mass 10, 20, 40, 150 and 250 kDa) were successfully loaded into and released from the thermogels. Drug-loaded polymer solutions were characterized for gelation behavior and micelle size. Drug loading increased the size of the multiblock co-polymer micelles from 20 to 100 nm. The co-polymer improved paclitaxel and camptothecin loading in an aqueous solution by 6900- and 1050-fold, respectively, compared to their solubility in water. The ther-mogels released loaded drugs in a pH-dependent fashion, regardless of their properties. At pH 5.0 and 6.5, paclitaxel and camptothecin completely released in 4 and 15 days, respectively, by a combined mechanism of diffusion and erosion. At neutral pH, diffusion predominated gel erosion to sustain the drug release up to 40 days. Fluorescein-labeled dextran release from the thermogels showed a similar pH-dependent trend as the hydrophobic small molecule drugs. However, dextran release at neutral pH was entirely dependent on the molecular mass of the dextran. Low-molecular-mass (10 and 20 kDa) dextrans were completely released in 12 and 21 days, respectively, while high-molecular-mass (⩾40 kDa) dextrans being continuously released over 36 days, indicating that the threshold of molecular weight necessary for sustained release of a hydrophilic macromolecule from this thermogel (e.g., enzymes, monoclonal antibodies and immunotoxins) is 40 kDa. Taken together, the MBCP thermogel showed potential as a controlled drug-delivery system that showed sustained release of both hydrophilic and lipophilic molecules.

Silk fibroin/poly(vinyl alcohol) photocrosslinked hydrogels for delivery of macromolecular drugs

Hydrogels are three-dimensional polymer networks widely used in biomedical applications as drug delivery and tissue engineered scaffolds to effectively repair or replace damaged tissue. In this paper we demonstrate a newly synthesized cytocompatible and drug releasing photo-crosslinked hydrogel based on poly(vinyl alcohol) methacrylate and silk fibroin which possesses tailorable structural and biological properties. The initial silk fibroin content was 0%, 10%, 20%, 30%, 40% and 50% with respect to the weight of poly(vinyl alcohol) methacrylate. The prepared hydrogels were characterized with respect to morphology, crystallinity, stability, swelling, mass loss and cytotoxicity. FITC–dextrans of different molecular weights were chosen as model drugs molecules for release studies from the hydrogels. The hydrogels containing different silk fibroin percentages showed differences in pore size and distribution. X-ray diffraction analysis revealed that amorphous silk fibroin in poly(vinyl alcohol) methacrylate is crystallized to β-sheet secondary structure upon gelation. The sol fraction increased with increasing fibroin concentration in the co-polymer gel (from 18% to 45%), although the hydrogel extracts were non-cytotoxic. Similarly, the addition of silk fibroin increased water uptake by the gels (from 7% to 21%). FITC–dextran release from the hydrogels was dependent on the silk fibroin content and the molecular weight of encapsulated molecules. The study outlines a newer type of photo-crosslinked interpenetrating polymer network hydrogel that possess immense potential in drug delivery applications.

Hydrogel of β-cyclodextrin-Grafted Polyethyleneimine: pH-Sensitive Release

Novel pH-sensitive hydrogels were prepared by grafting β-cyclodextrin (βCD) to polyethyleneimine (PEI) and cross-linking βCD using epichlorohydrin (EPI). While the molar ratio of βCD to PEI was kept to 1:50, the molar ratio of EPI to βCD was varied so that it was 3/1, 5/1, and 10/1. When the EPI to βCD ratio was higher, the degree of equilibrium swelling and the percentage release were lower, possibly due to a higher cross-linking density. The % release of blue dextran was much less than that of fluorescein isothiocyanate-dextran (FITC-dextran). The electrostatic interaction of blue dextran with the hydrogel is believed to suppress the release of the dye. Among the hydrogels prepared in this work, the hydrogel prepared using the βCD to EPI ratio of 1/5 was the most pH sensitive in terms of the degree of swelling and the degree of FITC-dextran release.

Magnetic field dependence of the diffusion of single dextran molecules within a hydrogel containing magnetite nanoparticles

We consider the effect of applied magnetic fields on the diffusion of single dextran molecules labeled with fluorescein isothiocyanate within a ferrogel [a composite of magnetite nanoparticles in a poly(methacrylic acid) hydrogel] using fluorescence correlation spectroscopy. We show that the mesh size of the ferrogel is controlled by the applied magnetic field, B, and scales as exp(-(4)√ξ(3)B(2)/2μ(0)k(B)T), where ξ is a correlation length, μ(0) the magnetic constant, k(B) the Boltzmann constant, and T is the absolute temperature. The diffusion coefficient of the dextran can be modeled with a simple Stokes-Einstein law, containing the same scaling behavior with magnetic field as the swelling of the hydrogel. Furthermore, the magnetic field-dependent release of dextran from the hydrogel is also controlled by the same relationship. The samples were characterized by small angle x-ray scattering (SAXS) and magnetometry experiments. Magnetic hysteresis loops from these ferrogels and zero field cooled∕field cooled measurements reveal single domain ferromagnetic behavior at room temperature with a similar coercivity for both as-prepared and fully swollen ferrogels, and for increasing magnetic nanoparticle concentration. SAXS experiments, such as the hysteresis loops, show that magnetite does not aggregate in these gels.

β -Cyclodextrin hydrogel incorporating hydrophobically modified poly(N -isopropylacrylamide) for a temperature-dependent release

Hydrogels exhibiting a temperature-dependent release were prepared by incorporating hydrophobically modified poly(N-isopropylacrylamide) (HmPNIPAM) into β-cyclodextrin hydrogels (β-CD hydrogels). The specific loading of HmPNIPAM was about 0.0069 g HmPNIPAM/g β-CD hydrogels. The incorporation of the polymer was qualitatively conformed by FT-IR spectroscopy and SEM. The percent release of blue dextran in 24 hr at 20°C (about 77%) was markedly higher than those obtained at 35°C and 45°C (about 53 and 55%, respectively). At the higher temperatures, the volume of the hydrogel could decrease upon the thermal contraction of HmPNIPAM, leading to a smaller mesh and a suppressed release. In fact, the swelling ratio in 24 hr at 35°C and 45°C (about 396% and 405%, respectively) was obviously lower than that obtained at 20°C (about 465%). Copyright © 2011 John Wiley & Sons, Ltd.

BH3 Domains other than Bim and Bid Can Directly Activate Bax/Bak

Bcl-2 family proteins regulate a critical step in apoptosis referred to as mitochondrial outer membrane permeabilization (MOMP). Members of a subgroup of the Bcl-2 family, known as the BH3-only proteins, activate pro-apoptotic effectors (Bax and Bak) to initiate MOMP. They do so by neutralizing pro-survival Bcl-2 proteins and/or directly activating Bax/Bak. Bim and Bid are reported to be direct activators; however, here we show that BH3 peptides other than Bim and Bid exhibited various degrees of direct activation of the effector Bax or Bak, including Bmf and Noxa BH3s. In the absence of potent direct activators, such as Bim and Bid, we unmasked novel direct activator BH3 ligands capable of inducing effector-mediated cytochrome c release and liposome permeabilization, even when both Bcl-xL- and Mcl-1-type anti-apoptotic proteins were inhibited. The ability of these weaker direct activator BH3 peptides to cause MOMP correlated with that of the corresponding full-length proteins to induce apoptosis in the absence of Bim and Bid. We propose that, in certain contexts, direct activation by BH3-only proteins other than Bim and Bid may significantly contribute to MOMP and apoptosis.

Anionic and cationic dextran hydrogels for post-loading and release of proteins

In this study, post-loading of proteins in and release from chemically crosslinked dextran hydrogels exploiting reversible electrostatic interactions was investigated. Methacrylated dextran (Dex-MA) was co-polymerized with methacrylic acid (MA) or dimethylaminoethyl methacrylate (DMAEMA) to form negatively and positively charged hydrogels, respectively. Incubation of negatively charged hydrogels in a low ionic strength (10 mM HEPES, pH 7.4) solution of cytochrome C (isoelectric point ( pI) 10.2) led to quantitative absorption of the protein in the hydrogel. BSA ( pI 4.8) and myoglobin ( pI 7.2) were post-loaded into positively charged gels at neutral pH and negatively charged gels at pH 5, respectively. Loading efficiency and protein distribution in the gels were dependent on network charge (maximum loading efficiency at 100–150 μmol charged monomer/g gel) and crosslink density (higher and more homogenous loading at lower crosslink density) and on the ionic strength during loading (lower but more homogenous loading at higher ionic strength). Diffusion controlled release of the loaded protein was triggered by incubation of the hydrogel in HEPES buffered saline (HBS) pH 7.4. The amount of released cytochrome C in HBS varied from 94% to 70% from gels containing 60 and 150 MA/g, respectively. Importantly, quantitative release was obtained in 1 M NaCl, indicating that post-loading led to neither the formation of insoluble protein aggregates nor irreversible immobilization of the protein in the matrix. ESI-MS analysis of the released cytochrome C revealed that post-loading did not result in oxidation of the protein, as opposed to loading during preparation of the gels. In conclusion, this paper shows that post-loading of proteins in dextran hydrogels and release exploiting reversible charge interactions can be applied for efficient loading of proteins that are negative, positive or neutral at physiological pH. Importantly, our data demonstrate that using this loading method no chemical modification to the protein occurred.

A MATHEMATICAL MODEL CHARACTERIZING THE DIFFUSION PROPERTIES OF MICROCAPSULES

In this article, we present a mathematical model to describe the diffusion of dextran through spherical microcapsules. Dextran was first allowed to diffuse into the microcapsules for a certain length of time (loading period). After the loading process was complete, the microcapsules were immersed in water medium, and the released concentration of dextran in the medium was measured over time. To demonstrate the applicability of the diffusion model, it was fit to the dextran release data (Gupta et al., 2004), and estimates of the diffusion coefficients in the core and wall of a microcapsule were obtained. From such estimates, one may be able to characterize the diffusion (or release) properties of microcapsules with different wall or membrane thicknesses, wall constitutions, loading times, and dextran molecular weights. Results from such a model can help in the planning and design of experiments.

PH-Dependent release of blue dextran from carboxymethyl-β-cyclodextrin hydrogels

Carboxymethyl-β-cyclodextrin (CM-β-CD) hydrogel was prepared by cross-linking β-CD and substituting the hydroxyl groups with carboxymethyl group. Epichlorohydrin (EPI) was used as a cross-linker and the molar ratio of EPI to β-CD was 10:1. The number of carboxymethyl group per β-CD residue was determined by a back-titration method and the value was 0.86. The swelling ratio of CM-β-CD hydrogel increased as the pH of medium increased. The carboxyl group will be ionized with increasing pH and an electrostatic repulsion developed within the hydrogels would be responsible for a higher swelling ratio at a higher pH. The degree of release of blue dextran from the hydrogel also increased as the pH of medium increased. The pH-dependent swelling ratio could account for the pH-sensitive release.

Niemann-Pick C1 Functions Independently of Niemann-Pick C2 in the Initial Stage of Retrograde Transport of Membrane-impermeable Lysosomal Cargo

The rare neurodegenerative disease Niemann-Pick Type C (NPC) results from mutations in either NPC1 or NPC2, which are membrane-bound and soluble lysosomal proteins, respectively. Previous studies have shown that mutations in either protein result in biochemically indistinguishable phenotypes, most notably the hyper-accumulation of cholesterol and other cargo in lysosomes. We comparatively evaluated the kinetics of [(3)H]dextran release from lysosomes of wild type, NPC1, NPC2, and NPC1/NPC2 pseudo-double mutant cells and found significant differences between all cell types examined. Specifically, NPC1 or NPC2 mutant fibroblasts treated with NPC1 or NPC2 siRNA (to create NPC1/NPC2 pseudo-double mutants) secreted dextran less efficiently than did either NPC1 or NPC2 single mutant cell lines, suggesting that the two proteins may work independently of one another in the egress of membrane-impermeable lysosomal cargo. To investigate the basis for these differences, we examined the role of NPC1 and NPC2 in the retrograde fusion of lysosomes with late endosomes to create so-called hybrid organelles, which is believed to be the initial step in the egress of cargo from lysosomes. We show here that cells with mutated NPC1 have significantly reduced rates of late endosome/lysosome fusion relative to wild type cells, whereas cells with mutations in NPC2 have rates that are similar to those observed in wild type cells. Instead of being involved in hybrid organelle formation, we show that NPC2 is required for efficient membrane fission events from nascent hybrid organelles, which is thought to be required for the reformation of lysosomes and the release of lysosomal cargo-containing membrane vesicles. Collectively, these results suggest that NPC1 and NPC2 can function independently of one another in the egress of certain membrane-impermeable lysosomal cargo.

Intraparticle Transport and Release of Dextran in Silica Spheres with Cylindrical Mesopores

The transport of oligomeric molecules in silica spheres with cylindrical mesopores has been quantified and related to the structural features of the spherical particles and the interactions at the solid-liquid interface. An emulsion-solvent evaporation method was used to produce silica spheres having cylindrical mesopores with an average pore diameter of 6.5 nm. The transport of dextran molecules (fluorescently tagged) with molecular weights of 3000 and 10,000 g/mol was quantified using confocal laser scanning microscopy (CLSM). The intraparticle concentration profiles in the dextran-containing spheres were flat at all times, suggesting that the release is not isotropic and not limited by diffusion. The release of dextran into the solution is characterized by an initial burst, followed by long-term sustained release. The release follows a logarithmic time dependency, which was rationalized by coupling concentration-dependent effective diffusion constants with adsorption/desorption.

A novel thermosensitive polymer with pH-dependent degradation for drug delivery

A class of thermosensitive biodegradable multiblock copolymers with acid-labile acetal linkages were synthesized from Pluronic ® triblock copolymers (Pluronic ® P85 and P104) and di-(ethylene glycol) divinyl ether. The novel polymers were engineered to form thermogels at body temperature and degrade in an acidic environment. The Pluronic ®-based acid-labile polymers were characterized using nuclear magnetic resonance, gel permeation chromatography and differential scanning calorimetry. In vitro biocompatibility of the synthesized polymers was evaluated using calorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The polymers showed reverse thermogelling behavior in water around body temperature. The sol–gel transition temperatures of the polymers synthesized from Pluronic ® P85 and P104 were lowered from 70.3 to 30 °C and from 68.5 to 26.9 °C, respectively, when the synthesized polymers were compared with corresponding Pluronic ® block copolymers at a concentration of 25 wt.%. The hydrophobic dye solubilization confirmed the formation of polymeric micelles in the aqueous solution. The sizes of the multiblock copolymers increased on a rise in temperature, indicating that thermal gelation was mediated by micellar aggregation. The thermally driven hydrogels showed preferential polymer degradation at acidic pH. At pH 5.0 and 6.5, the release of 40 kDa fluorescein isothiocyanate–dextran (FITC–dextran) from the thermally formed hydrogels was completed within 2 and 9 days, respectively. However, FITC–dextran was continuously released up to 30 days at neutral pH. The mechanism of FITC–dextran release at pH 5.0 was mainly an acid-catalyzed degradation, whereas both diffusion and pH-dependent degradation resulted in FITC–dextran release at pH 6.5. The novel polymers hold great potential as a pH-sensitive controlled drug delivery system owing to their interesting phase transition behavior and biocompatibility.

Preparation and characterization of protein loaded microspheres based on a hydroxylated aliphatic polyester, poly(lactic-co-hydroxymethyl glycolic acid)

The purpose of this study was to investigate the suitability of a novel hydroxylated aliphatic polyester, poly(lactic-co-hydroxymethyl glycolic acid) (PLHMGA), as controlled release system for pharmaceutical proteins. Dextran Blue (as a macromolecular model compound) and lysozyme-loaded PLHMGA and PLGA (control formulation) microspheres were prepared by a solvent evaporation technique. The Dextran Blue and lysozyme loaded PLHMGA microspheres prepared with 10% polymer solution showed, because of a high porosity, a high burst release (35–75%) and the remaining content was released in a sustained manner for 15–20 days. The microspheres prepared with 15 and 20% polymer solution had a lower porosity and showed a pulsed release after day 8 and in 27 days they released more than 90% of Blue Dextran. The release of lysozyme was incomplete, likely due to aggregation of part of the encapsulated protein. Spectroscopic analysis of the released lysozyme indicated fully preserved secondary/tertiary structure and an enzyme activity assay showed that the specific activity of the released protein was maintained. An in vitro degradation study showed that the release of Blue Dextran and lysozyme is essentially controlled by the degradation of the microspheres. This study shows that microspheres made of the hydroxylated aliphatic polyester, poly(lactic-co-hydroxymethyl glycolic acid), are promising systems for the controlled release of pharmaceutical proteins.

MODELING MASS TRANSFER OF FITC-LABELED DEXTRAN FROM POLYELECTROLYTE MICROCAPSULES

Layer-by-layer adsorption of oppositely charged polyelectrolytes has been used for the manufacturing of hollow microspheres or capsules for controlled release studies. Using this self-assembly technique, microsphere core material was encapsulated with poly styrenesulfonate (PSS) and poly allylamine (PAH) multilayers or PAH and polyvinyl sulfate (PVS) multilayers and the core dissolved to produce hollow microcapsules. The microspheres were loaded with fluorescein-isothiocyanate (FITC)-labeled dextran of different molecular weights for different lengths of time to quantify the release properties. After loading, the capsules were immersed in water and the FITC-dextran was allowed to diffuse into the mother liquor. The FITC-dextran concentration of the mother liquor was measured over a period of hours and days. In this study, one- and two-compartment models were developed, based on a species mass balance, to predict the concentration of dextran release from the microcapsules over time. The two-compartment model was found to be superior to the one-compartment model in its fit to the observed data. The model was applied to experimental data in order to characterize the release properties of microcapsules with different numbers of layers and constituent architectures.

A microscopic view on photo-induced polyplex release from endosomes

Abstract summary Photoinduced endosomal release of dextran and LPEI, PLL and PDL polyplexes was examined by means of real time fluorescence microscopy. Dextran was released within 100 ms and diffused freely throughout the cytoplasm. Polyplexes showed distinguishable release patterns due to differences in DNA condensation and biodegradability. In addition, cellular effects of the photosensitizer on microtubules and endosomal movement were observed.

Release behavior of freeze‐dried alginate beads containing poly(N‐isopropylacrylamide) copolymers

AbstractBeads composed of alginate, poly(N‐isopropylacrylamide) (PNIPAM), the copolymers of N‐isopropylacrylamide and methacrylic acid (P(NIPAM‐co‐MAA)), and the copolymers of N‐isopropylacrylamide, methacrylic acid, and octadecyl acrylate (P(NIPAM‐co‐MAA‐co‐ODA)), were prepared by dropping the polymer solutions into CaCl2 solution. The beads were freeze‐dried and the release of blue dextran entrapped in the beads was observed in distilled water with time and pH. The degree of release was in the order of alginate bead < alginate/PNIPAM bead ≈ alginate/P(NIPAM‐co‐MAA) bead < alginate/P(NIPAM‐co‐MAA‐co‐ODA) bead. On the other hand, swelling ratios reached steady state within 20 min, and the values were 200–800 depending on the bead composition. The degree of swelling showed the same order as that of release. Among the beads, only alginate/P(NIPAM‐co‐MAA‐co‐ODA) bead exhibited pH‐dependent release. At acidic condition, inter‐ and intraelectrostatic repulsion is weak and P(NIPAM‐co‐MAA‐co‐ODA) could readily be assembled into an aggregate due to the prevailing hydrophobic interaction of ODA. Thus, it could block the pore of bead matrix, leading to a suppressed release. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008