Magnetite/poly(alkylcyanoacrylate) (core/shell) nanoparticles as 5-Fluorouracil delivery systems for active targeting

In this article, a reproducible emulsion polymerization process is described to prepare core/shell colloidal nanospheres, loaded with 5-Fluorouracil, and consisting of a magnetic core (magnetite) and a biodegradable polymeric shell [poly(ethyl-2-cyanoacrylate), poly(butylcyanoacrylate), poly(hexylcyanoacrylate), or poly(octylcyanoacrylate)]. The heterogeneous structure of these carriers can confer them both the possibility of being used as drug delivery systems and the responsiveness to external magnetic fields, allowing an active drug targeting without a concurrent systemic distribution. Zeta potential determinations as a function of ionic strength showed that the surface behaviour of the core/shell particles is similar to that of pure cyanoacrylate particles. The first magnetization curve of both magnetite and magnetite/polymer particles demonstrated that the polymer shell reduces the magnetic responsiveness of the particles, but keeps unchanged their ferrimagnetic character. Two drug loading mechanisms were studied: absorption or entrapment in the polymeric network, and surface adsorption. We found that the acidity of the medium had significant effects on the drug absorption per unit mass of polymer, and needs to be controlled to avoid formation of macroaggregates and to reach significant 5-Fluorouracil absorption. The type of polymer and the drug concentration are also main factors determining the drug incorporation to the core/shell particles. 5-Fluorouracil release evaluations showed a biphasic profile affected by the type of polymeric shell, the type of drug incorporation and the amount of drug loaded.     

Ftorafur loading and controlled release from poly(ethyl-2-cyanoacrylate) and poly(butylcyanoacrylate) nanospheres

In the present work, a method is described to prepare polymeric colloidal nanospheres, consisting of poly(ethyl-2-cyanoacrylate) (PE-2-CA) or poly(butylcyanoacrylate) (PBCA), loaded with the anticancer drug ftorafur. The method is based on the anionic polymerization procedure, often used in the synthesis of poly(alkylcyanoacrylate) nanospheres for drug delivery. A detailed investigation of the capabilities of both polymeric nanoparticles to load this drug is shown. The effect of synthesis residuals and degradation products on the absorbance of supernatants was considered in the loading and release measurement methodologies, because of their potential perturbing influence on the determination of ftorafur concentration in solution. We found the existence of two mechanisms of drug incorporation: absorption or entrapment in the polymeric network, and surface adsorption, detectable by means of zeta potential and spectrophotometric measurements. Among the factors affecting the drug incorporation to the polymer network, the type of polymer, the pH and the drug concentration are the main determining ones. Moreover, the acidity of the medium needs to be controlled in order to avoid the formation of macroaggregates of solids. The optimum loading conditions were used to perform ftorafur release evaluations from polymeric particles, and the influence of the mechanism of drug incorporation, the amount of drug loaded, and the type of polymer on the drug release were studied.     

Freeze-drying of liposomes using tertiary butyl alcohol/water cosolvent systems

Polyacrylamide (pAAm) particles crosslinked with N,N-methylenebis-acrylamide/ethylene glycol dimethacrylate (NNMBA/EGDMA) have been prepared in water–methanol medium by the dispersion polymerization using poly(vinyl pyrrolidone), PVP as a steric stabilizer. 5-fluorouracil an anticancer drug, has been loaded in situ into the crosslinked pAAm particles. Plain as well as drug loaded microparticles have been characterized by differential scanning calorimetry (DSC) and X-ray diffraction studies (XRD) and scanning electron microscopy (SEM). DSC and XRD studies have indicated a molecular level dispersion of the drug in pAAm particles during in situ loading and SEM pictures have shown the formation of spherical and oval-shaped particles. In vitro release of 5-fluorouracil from the crosslinked pAAm particles has been carried out in 7.4 pH buffer medium. Both encapsulation efficiency and release patterns are found to depend on the nature of the crosslinking agent, amount of crosslinking agent used and the amount of drug loaded. In vitro release studies indicated the controlled release of 5-fluorouracil up to 12 h.     

Development of carbonyl iron/ethylcellulose core/shell nanoparticles for biomedical applications

A reproducible method for the preparation of mixed colloidal nanoparticles, consisting of a magnetic carbonyl iron nucleus and a biocompatible ethylcellulose latex shell, is described in this article. The heterogeneous structure of the particles can confer them both the possibility of being used as drug delivery systems and the responsiveness to external magnetic fields, allowing a selective guidance of drug molecules to specific target tissues without a concurrent increase in its level in healthy tissues. The preparation method is based on an emulsion solvent evaporation process. A complete physicochemical characterization of the composite particles was carried out, and this preliminary investigation showed that the surface behavior of the core/shell particles is similar to that of bare ethylcellulose particles. This was confirmed, in particular, by zeta potential determinations as a function of pH and ionic strength. This fact points to the ethylcellulose shell efficiently coating carbonyl iron, and leading to composite particles which, from the electrokinetic point of view, are almost indistinguishable from latex. The thermodynamic analysis agrees with the electrokinetic one in suggesting that the coverage has been complete, since the components of the surface free energy of mixed particles coincide almost exactly with those corresponding to the cellulose-based pseudolatex. Moreover, the hydrophilic nature of carbonyl iron is modified and the particles become hydrophobic, just like the latex, when they are covered by ethylcellulose. The magnetic behaviors of the carbonyl iron and composite particles were also checked, and the similarities between both types of particles were demonstrated, except that the polymeric shell reduces the magnetization of the sample.     

PCL/PEG core/sheath fibers with controlled drug release rate fabricated on the basis of a novel combined technique

A novel core/sheath fiber preparation method, which included the processes of blend electrospinning to produce the core fiber and UV-induced graft polymerization to fabricate the outer polymeric shell, was presented to provide designated fibers with different shell thicknesses. A hydrophilic drug, salicylic acid (SA), was loaded in the representative poly(?-caprolactone) (PCL)/polyethylene glycol (PEG) core/sheath fibers, performed according to this combined technique. FTIR analysis indicated that the existence of hydrogen bonds between SA and the PCL matrix improved drug compatibility. Field emission scanning electron microscopy (FESEM) images indicated that the morphology and the diameter distribution of fibers changed significantly after the graft polymerization procedure. All the core/sheath fibers became more flexible and thicker compared with the core fiber. The water contact angle (WCA) test also noted the differences of these two fibers: PCL/PEG core/sheath fibers with cross-linked PEG surface exhibited more hydrophilic property. Moreover, in vitro SA release tests were conducted to explore the relationship between the PEG shell thickness and the drug release rate. A typical biphasic release mechanism was observed for the PCL/PEG core/sheath fibers, and their sustained release rates were controlled by the PEG shell thickness in a linear correlation.     

Preparation, characterization and dielectric studies on carbonyl iron/cellulose acetate hydrogen phthalate core/shell nanoparticles for drug delivery applications

A method to prepare composite colloidal nanoparticles, consisting of a magnetic core (carbonyl iron) and a biodegradable polymeric shell (cellulose acetate hydrogen phthalate) was described and also particle size was characterized by Optical Microscope and Scanning Electron Microscopy. Dielectric properties of Cellulose Acetate Hydrogen Phthalate (CAP) and carbonyl iron/CAP (core/shell) tablets were studied in the frequency range of 70 Hz-400 kHz at 300 K using LCR meter and compared the dielectric parameters of core/shell and ordinary phase of CAP tablets. From the dielectric results, the importance of core/shell nanoparticles in controlled drug delivery was discussed.     

酸敏性葡聚糖纳米凝胶的制备与释药性质考察

目的制备具有酸敏特性的聚（甲基丙烯酸缩水甘油酯修饰葡聚糖,dex GMA）/（丙烯酸,AAc）纳米凝胶,研究其降解和释药性质。方法乳液聚合法制备poly(dex GMA/AAc)纳米凝胶,测定不同pH值下的粒度分布,以红霉素（EM）为药物模型,动态透析法测定纳米凝胶在不同pH值下的释药性质。结果poly(dex GMA/AAc)纳米凝胶的平均粒径约为100 nm,包裹率、载药率分别为90.7%和1.06%。在无酶人工胃液 (SGF) 2 h纳米凝胶的药物累积释放率分别为7.0%,之后在无酶人工肠液(SIF)里4 h 内增加到37.0%。结论poly(dex GMA/AAc)纳米凝胶具有酸敏特性,在SGF里释放少量药物,在SIF里凝胶溶胀、降解,药物释放量明显增大。poly(dex GMA/AAc)纳米凝胶是潜在的结肠靶向载体。     

Effect of formulation and processing variables on the characteristics of microspheres for water-soluble drugs prepared by w/o/o double emulsion solvent diffusion method

80% except for acetaminophen, due to its lower solubility in water and higher solubility in corn oil. The release profile of the drug was pH dependent. In acidic medium, the release rate was much slower, however, the drug was released quickly at pH 7.4. Tacrine showed unexpected release profiles, probably due to ionic interaction with polymer matrix and the shell structure and the highest release rate was obtained at pH 2.0. The prepared microspheres had a sponge-like inner structure with or without central hollow core and the surface was dense with no apparent pores.     

Ciproflexacin-loaded polyisobutylcyanoacrylate nanoparticles: Preparation and characterization

Experimental conditions for attachment of ciprofloxacin hydrochloride to poly(isobutylcyanoacrylate) (PIBCA) nanoparticles (NP) and release of drug were studied. Attachment of the drug was performed by the incorporative and adsorptive processes. The pH, and to a lesser degree the drug concentration in the reaction medium, were shown to be important factors in controlling the size of NP only in the incorporative process. The diameter of NP increased when the initial drug concentration was higher than 1.2 mg/ml. Ciproflaxacin content of NP was influenced by the drug concentration in the polymerization and incubation media. The binding capacity in the adsorptive process was not influenced by the pH. In contrast, the entrapment of ciprofloxacin in the NP by incorporation was greatly influenced by the pH in the range 1.5-4. Thin layer chromatography (TLC) of NP prepared by incorporation showed new products suggesting interactions between ciprofloxacin and isobutylcyanoacrylate. Ciprofloxacin release from nanoparticles prepared by the incorporating process was found to be slower as compared to nanoparticles produced by adsorptive process from which the drug release was practically complete within 1 h in absence of esterases in the release medium. Drug release from the two types of NP was accelerated in the presence of esterases in the release medium.     

Novel PLA modification of organic microcontainers based on ring opening polymerization: synthesis, characterization, biocompatibility and drug loading/release properties

In the current study, poly lactic acid (PLA) modified hollow crosslinked poly(hydroxyethyl methacrylate) (PHEMA) microspheres have been prepared, in order to obtain a stimulus-responsive, biocompatible carrier with sustained drug release properties. The synthetical process consisted of the preparation of poly(methacrylic acid)@poly(hydroxyethyl methacrylate-co-N,N'-methylene bis(acrylamide)) microspheres by a two stage distillation-precipitation polymerization technique using 2,2'-azobisisobutyronitrile as initiator. Following core removal, a PLA coating of the microspheres was formed, after ring opening polymerization of DL-lactide, attributing the initiator's role to the active hydroxyl groups of PHEMA. The anticancer drug daunorubicin (DNR) was selected for the study of loading and release behavior of the coated microspheres. The loading capacity of the PLA modified microspheres was found to be four times higher than that of the parent ones (16% compared to 4%). This coated microspherical carrier exhibited a moderate pH responsive drug release behavior due to the pH dependent water uptake of PHEMA, and PLA hydrolysis. The in vitro cytotoxicity of both the parent and the DNR-loaded or empty modified hollow microspheres has been also examined on MCF-7 breast cancer cells. The results showed that although the empty microspheres were moderately cytotoxic, the DNR-loaded microspheres had more potent anti-tumor effect than the free drug. Therefore, the prepared coated microspheres are interesting drug delivery systems.     

Controlled release of lipase from Candida rugosa loaded into hydrogels of N-isopropylacrylamide and itaconic acid

The series of poly(N-isopropylacrylamide-co-itaconic acid) hydrogels, with lipase from Candida rugosa as a model protein, were synthesized by free radical copolymerization. The composition of hydrogels was varied by monomers ratio, crosslinking agent concentration and amounts of lipase, which was loaded by in situ polymerization. All samples were characterized regarding morphology. The investigation of hydrogel swelling properties revealed their pH and temperature sensitive character. Protein loading efficiency, release profiles and the specific activity yield of the released lipase were also investigated as a function of hydrogel composition, protein content and pH, at the physiological temperature of 37°C. Copolymers of N-isopropylacrylamide and itaconic acid presented high lipase loading efficiency. Another very important feature of these copolymers was that the protein release kinetic strongly depended on the pH value of the medium. The diffusion exponents values around 1 denoted that these hydrogel compositions could be adjusted to follow near zero-order kinetics. Namely, hydrogel formulations released low amounts of lipase at pH 2.20, but much higher released protein quantities were observed at pH 6.80 enabling these copolymers to be attractive candidates as site specific protein oral drug delivery systems.     

Bupivacaine-loaded biodegradable poly(lactic-co-glycolic) acid microspheres I. Optimization of the drug incorporation into the polymer matrix and modelling of drug release

Bupivacaine has been encapsulated by solvent evaporation method based on O/W emulsion, using poly(DL-lactic-co-glycolic) acid (PLGA) 50:50. The particle size can be controlled by changing stirring rate and polymer concentration. The encapsulation efficiency was affected by polymer concentration and burst effect of bupivacaine released from particles was affected by drug/polymer mass ratio. Orthogonal design was used to optimize the formulation according to drug content, encapsulation efficiency and burst effect. The dissolution profile and release model were evaluated with two different bupivacaine microspheres (bupi-MS) groups including low drug loading (6.41%) and high drug loading (28.92%). It was observed that drug release was affected by drug loading especially the amount of drug crystal attached on surface of bupi-MS. The drug release profile of low drug loaded bupi-MS agreed with Higuchi equation and that of high drug loaded bupi-MS agreed with first order equation.     

Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate) micelles for rapamycin delivery: in vitro characterization and biodistribution

Our objective was to synthesize an amphiphilic diblock copolymer for micellar delivery of rapamycin. Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonyl-propylene carbonate) (PEG-b-PBC) with different hydrophobic core lengths were synthesized from methoxy poly(ethylene glycol) and 2-methyl-2-benzoxycarbonyl-propylene carbonate through ring-opening polymerization using 1,8-diazabicycloundec-7-ene as a catalyst. The critical micelle concentration of PEG-b-PBC was around 10(-8) M and depends on the hydrophobic core length. Rapamycin was effectively incorporated into micelles and drug loading increased with increasing hydrophobic core length, with maximal drug loading of 10% (w/w, drug/polymer), drug loading efficiency of about 85%, and mean particle size of around 70 nm. The drug release profile was also dependent on the hydrophobic core length and the drug release from PEG(114) -b-PBC(30) micelles was the slowest. We also determined the toxicity of rapamycin micelles on insulinoma (INS-1E) β-cells and human islets. Encapsulation of rapamycin into PEG-b-PBC micelles reduced its toxicity. Biodistribution of rapamycin-loaded PEG-b-PBC micelles was determined after systemic administration into mice. Rapamycin-loaded PEG-b-PBC micelles showed little difference in pharmacokinetics and biodistribution characteristics in mice compared with rapamycin carrying nanosuspension. In conclusion, rapamycin formulated with PEG-b-PBC micelles showed significantly reduced toxicity on INS-1E β-cells and human islets, but had similar biodistribution profiles as those of nanosuspensions.     

pH-responsive polymeric micelles of poly(ethylene glycol)-b-poly(alkyl(meth)acrylate-co-methacrylic acid): influence of the copolymer composition on self-assembling properties and release of candesartan cilexetil.

The objective of the present study was to investigate the influence of chemical structure and molecular weight of pH-sensitive block copolymers on their self-assembling properties, the loading and the release of candesartan cilexetil (CDN). Block copolymers of poly(ethylene glycol) and t-butyl methacrylate, iso-butyl acrylate, n-butyl acrylate or propyl methacrylate were synthesized by atom transfer radical polymerization. pH-sensitivity was obtained by hydrolysis of t-butyl groups. The poorly water-soluble drug CDN was incorporated in the micelles and the in vitro drug release was evaluated as a function of pH. The critical aggregation concentration of hydrolyzed copolymers (pK(a)=6.2-6.6) was higher compared to the unhydrolyzed ones. Dynamic light scattering studies and atomic force microscopy images revealed uniform size micelles with aggregation numbers ranging from 60 to 160. The entrapment efficiency of CDN was generally found to be above 90%, with drug loading levels reaching approximately 20% (w/w). Differential scanning calorimetry studies showed the amorphous nature of entrapped CDN. The release of CDN from pH-sensitive micelles was triggered upon an increase in pH from 1.2 to 7.2. These findings suggest that the PEG-b-poly(alkyl(meth)acrylate-co-methacrylic acid)s can self-assemble to form micelles which exhibit high loading capacities for CDN and release the drug in a pH-dependent fashion.     

Combined hydroxypropyl-beta-cyclodextrin and poly(alkylcyanoacrylate) nanoparticles intended for oral administration of saquinavir

The aim of this study was to prepare and characterize an hydroxypropyl-beta-cyclodextrin-saquinavir inclusion complex with the purpose of incorporating this complex into poly(alkylcyanoacrylate) nanoparticles in order to increase the drug loading. Hydroxypropyl-beta-cyclodextrin-saquinavir complex was characterized by thermal (differential scanning calorimetry), crystallographic (X-ray diffractography) and spectroscopic methods (circular dichroism, H1-NMR). Nanoparticles were prepared by polymerization of alkylcyanoacrylate monomers (isobutyl- and isohexylcyanoacrylate) in a water solution of the complex and further characterized. The apparent solubility of saquinavir was increased 400-fold at pH 7.0 in presence of hydroxypropyl-beta-cyclodextrin owing to the formation of a drug-cyclodextrin complex as demonstrated mainly by 1H NMR and confirmed by other techniques. Saquinavir-loaded nanoparticles could be easily prepared in the presence of a drug-cyclodextrin complex. It was found that large amounts of cyclodextrins remained associated with the particles, resulting in a 20-fold increase in saquinavir loading compared to nanoparticles prepared in the absence of cyclodextrins. This study has shown that the loading in saquinavir of poly(alkylcyanoacrylate) nanospheres could be dramatically improved by simultaneously increasing the apparent solubility of the drug in the preparation medium and the amount of cyclodextrin associated with the particles, making these nanospheres a promising system for oral application.     

Microencapsulation using poly(L-lactic acid) IV: Release properties of microcapsules containing phenobarbitone

Microcapsules containing phenobarbitone were prepared from poly(L-lactic acid), using a water/oil emulsification and evaporation process. Polymers of three different molecular weights were used. Particle size was found to increase with an increase in core loading and polymer molecular weight. Release studies were carried out at buffer pHs of 2 and 9 at 37 degrees C. The release mechanism was found to follow a square root of time relationship. Almost 90 per cent of the phenobarbitone was released within 2 h. The release rate was not a direct relationship with the phenobarbitone content of the microcapsules because of the differing size and surface area of the microcapsules. However, normalized release rates (release rate/specific surface area) were found to increase linearly with the increase in phenobarbitone content. First order release plots of the data were not found consistent with the core loading. The release at a buffer pH of 9 was very rapid and with some microcapsules was faster than solution of the uncoated crystalline phenobarbitone. At pH 2 release was also very rapid, due to the presence of large pores in the microcapsules of high molecular weight polymers. Release from the microcapsules prepared from low molecular weight polymer was slower than those from high molecular weight polymers. Microcapsules from the low molecular weight polymer were found to swell in the dissolution medium and finally disintegrated into smaller fragments.     

WITHDRAWN: 5-Fluorouracil-loaded iron/ethylcellulose (core/shell) nanoparticles for active targeting of cancer

Even though 5-fluorouracil has been demonstrated to display antitumor activity against a wide variety of cancers, it is needed to be administered at high doses to elicit the required therapeutic activity, simultaneously leading to severe side effects. We hypothesized that the efficient delivery of 5-fluorouracil to tumors using a magnetic colloid could reduce the dose required to bring out sufficient therapeutic response. Thus, we have formulated a 5-fluorouracil-loaded magnetic nanomedicine consisting of a magnetic core (iron) and a biocompatible polymeric shell (ethylcellulose), suitable for parenteral administration. These core/shell nanoparticles were synthesized by an emulsion solvent evaporation process. Two drug loading methods were analyzed: the first one based on 5-fluorouracil surface adsorption onto the preformed nanoparticles, and the second method being drug addition prior to the emulsion solvent evaporation process leading to drug entrapment into the polymeric network. 5-Fluorouracil entrapment into the polymeric matrix yielded a higher drug loading and a slower drug release profile as compared with drug adsorption. Finally, as a proof of concept, Prussian blue staining has demonstrated the considerable accumulation of these magnetically guided composite nanoparticles in the tumors, suggesting the potential of this stimuli-sensitive drug carrier for the efficient treatment of cancer by active targeting.     

Release dynamics of ciprofloxacin from swellable nanocarriers of poly(2-hydroxyethyl methacrylate): an in vitro study

Swellable polymeric nanosystems have emerged as promising materials in drug release technologies. Such systems have shown potential in releasing antibiotic drugs and to do so controllably. In the present investigation poly(2-hydroxyethyl methacrylate) nanoparticles were synthesized by suspension polymerization of 2-hydroxyethyl methacrylate and characterized by various techniques such as Fourier transform–infrared spectrometry, scanning electron microscopy, particle size analysis, and surface charge measurements. The synthesized nanoparticles were swellable in water and showed promise to function as a swelling controlled-release system. The release kinetics of drug-loaded particles was studied in phosphate-buffered saline (PBS) using ciprofloxacin as a model antibacterial drug. The chemical stability of the pure and released drug was also assessed in PBS (pH 7.4), acidic (pH 1.8), and alkaline (pH 8.6) solutions. The in vitro blood compatibility of nanoparticles was also investigated in terms of hemolysis tests. The drug-loaded nanoparticles were also examined for their antibacterial and blood-compatible behaviors.From the Clinical EditorSwellable polymeric nanosystems have emerged as promising materials in drug release technologies. In this paper, the release kinetics, antimicrobial properties and in vitro “blood compatibility” is reported for a specific swellable polymeric nanosystem.     

Mucoadhesive hydrogel microparticles based on poly (methacrylic acid-vinyl pyrrolidone)-chitosan for oral drug delivery

The study was aimed at the evaluation of N-vinyl pyrrolidone (NVP) incorporated polymethacrylic acid-chitosan microparticles for oral drug delivery applications. Poly (methacrylic acid)-chitosan (PMC) and poly(methacrylic acid-vinyl pyrrolidone)-chitosan (PMVC) microparticles were prepared by an ionic-gelation method. Mucoadhesion behaviour of these particles was evaluated by ex-vivo adhesion method using freshly excised rat intestinal tissue. Cytotoxicity and absorption enhancing property of PMC and PMVC particles were evaluated on Caco 2 cell monolayers. Protease enzyme inhibition capability and insulin loading/release properties of these hydrogel particles was evaluated under in vitro experimental conditions. Addition of NVP units enhanced the mucoadhesion behavior of PMC particles on isolated rat intestinal tissue. Both PMC and PMVC particles were found non-toxic on Caco 2 cell monolayers and PMC particles was more effective in improving paracellular transport of fluorescent dextran across Caco 2 cell monolayers as compared to PMVC particles. However, protease inhibition efficacy of PMC particles was not significantly affected with NVP addition. NVP incorporation improved the insulin release properties of PMC microparticles at acidic pH. Hydrophilic modification seems to be an interesting approach in improving mucoadhesion capability of PMC microparticles.     

Albumin release from biodegradable hydrogels composed of dextran and poly(ethylene glycol) macromer

Biodegradable hydrogels based on glycidyl methacrylate dextran (GMD) and dimethacrylate poly(ethylene glycol) (DMP) were proposed for colon-specific drug delivery. GMD was synthesized by coupling of glycidyl methacrylate with dextran in the presence of 4-(N,N-dimethyl-amino)pyridine (DMAP) using dimethylsulfoxide as a solvent. Methacrylate-terminated poly (ethylene glycol) (PEG) macromer was prepared by the reaction of PEG with methacryloyl chloride. GMD/DMP hydrogels were prepared by radical polymerization of phosphate buffer solution (0.1M, pH 7.4) of GMD and DMP, using ammonium peroxydisulfate (APS) and UV as initiating system. The synthetic GMD, DMP, and GMD/DMP hydrogels were characterized by fourier transform infrared (FT-IR) spectroscopy. The FITC-albumin loaded hydrogels were prepared by adding FITC-albumin solution before UV irradiation. Swelling capacity of GMD/DMP hydrogels was controlled not only by molecular weight of dextran, but also by incorporation ratio of DMP Degradation of the hydrogels has been studied in vitro with dextranase. FITC-albumin release from the GMD/DMP hydrogels was affected by molecular weight of dextran and the presence of dextranase in the release medium.