pH dependent poly[2-(methacryloyloxyethyl)trimetylammonium chloride-co-methacrylic acid]hydrogels for enhanced targeted delivery of 5-fluorouracil in colon cancer cells

Stimuli responsive hydrogels have shown enormous potential as a carrier for targeted drug delivery. In this study we have developed novel pH responsive hydrogels for the delivery of 5-fluorouracil (5-FU) in order to alleviate its antitumor activity while reducing its toxicity. We used 2-(methacryloyloxyethyl) trimetylammonium chloride a positively charged monomer and methacrylic acid for fabricating the pH responsive hydrogels. The released 5-FU from all except hydrogel (GEL-5) remained biologically active against human colon cancer cell lines [HT29 (IC₅₀ = 110–190 μg ml^?1) and HCT116 (IC₅₀ = 210–390 μg ml^?1)] but not human skin fibroblast cells [BJ (CRL2522); IC₅₀ ≥ 1000 μg ml^?1]. This implies that the copolymer hydrogels (1–4) were able to release 5-FU effectively to colon cancer cells but not normal human skin fibroblast cells. This is probably due to the shorter doubling time that results in reduced pH in colon cancer cells when compared to fibroblast cells. These pH sensitive hydrogels showed well defined cell apoptosis in HCT116 cells through series of events such as chromatin condensation, membrane blebbing, and formation of apoptotic bodies. No cell killing was observed in the case of blank hydrogels. The results showed the potential of these stimuli responsive polymer hydrogels as a carrier for colon cancer delivery.     

Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B₁₂ and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B₁₂ and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).     

Rapidly in situ forming adhesive hydrogel based on a PEG-maleimide modified polypeptide through Michael addition

Polyethylene glycol-maleimide modified ε-polylysine (EPL-PEG-MAL) with a unique comb-shaped structure was designed and used as a novel crosslinker for thiolated chitosan (CSS). Novel polysaccharide/polypeptide bionic hydrogels based on CSS and EPL-PEG-MAL could form rapidly in situ within 1 min via Michael addition under physiological conditions. Rheological studies showed that introduction of PEG can dramatically improve the storage modulus (G′) of the hydrogels and the optimal hydrogel system showed superior G′ of 1,614 Pa. The maximum adhesion strength reached 148 kPa, six times higher than that of fibrin glue. Cytotoxicity test indicated that the hydrogel is nontoxic toward growth of L929 cells. Gelation time, swelling ratio, storage modulus and adhesion strength of the hydrogels can be modulated by the content of PEG-maleimide, CSS concentration and molar ratio of maleimide group to thiol group. Benefiting from the fast gelation behaviors, desirable mechanical properties, relatively high adhesive performance and no cytotoxicity, these hydrogels have the potential applications as promising biomaterials for tissue adhesion and sealing.     

Poly (vinyl alcohol) hydrogels for pH dependent colon targeted drug delivery

Oral drug administration is convenient with pH dependent drug delivery system since the drug has to pass through different pH environments in gastro intestinal (GI) tract. The pH dependent swelling/shrinking behavior of hydrogel drug carrier controls the drug release without affecting the function of drug. pH dependent hydrogels of poly (vinyl alcohol) (PVA) were prepared by cross linking with maleic acid (MA). The hydrogels were characterized by attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, DSC, porosimetry, SEM, TEM, biocompatibility study and by measuring their swelling behavior in water, simulated gastric fluid (SGF) and intestinal fluid (SIF). Swelling of the hydrogels was found to be highest in SIF (pH: 7.5) and lowest in SGF (pH: 1.2) resembling that required in colon targeted drug delivery systems. Since the swelling behavior of the gel is pH dependent, these hydrogels were studied for colon targeted drug delivery in an in-vitro set-up resembling the condition of GI tract. The ratio of PVA and MA in the hydrogel was varied to study the effect on the drug diffusion rate. For drug delivery study, vitamin B12 and salicylic acid were used as model drugs. The hydrogel, loaded with model drugs vitamin B12 and salicylic acid also demonstrated colon specific drug release with a relatively higher drug release in SIF (pH: 7.5) than that in SGF (pH: 1.2).     

Thermoresponsive hyperbranched copolymer with multi acrylate functionality for in situ cross-linkable hyaluronic acid composite semi-IPN hydrogel

Thermoresponsive polymers have been widely used for in situ formed hydrogels in drug delivery and tissue engineering as they are easy to handle and their shape can easily conform to tissue defects. However, non-covalent bonding and mechanical weakness of these hydrogels limit their applications. In this study, a physically and chemically in situ cross-linkable hydrogel system was developed from a novel thermoresponsive hyperbranched PEG based copolymer with multi acrylate functionality, which was synthesized via an ‘one pot and one step’ in situ deactivation enhanced atom transfer radical co-polymerization of poly(ethylene glycol) diacrylate (PEGDA, M_n = 258 g mol⁻¹), poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, M_n = 475 g mol⁻¹) and (2-methoxyethoxy) ethyl methacrylate (MEO₂MA). This hyperbranched copolymer was tailored to have the lower critical solution temperature to form physical gelation around 37°C. Meanwhile, with high level of acrylate functionalities, a chemically cross-linked gel was formed from this copolymer using thiol functional cross-linker of pentaerythritol tetrakis (3-mercaptopropionate) (QT) via thiol-ene Michael addition reaction. Furthermore, a semi-interpenetrated polymer networks (semi-IPN) structure was developed by combining this polymer with hyaluronic acid (HA), leading to an in situ cross-linkable hydrogel with significantly increased porosity, enhanced swelling behavior and improved cell adhesion and viability both in 2D and 3D cell culture models.     

Hydroxybutyl chitosan thermo-sensitive hydrogel: a potential drug delivery system

Drug delivery mediated by hydrogel has shown great promise in controlled drug release field. We report here the development of a hydroxybutyl chitosan (HBC) thermo-sensitive gel to deliver doxorubicine hydrochloride (DOX·HCl) for cancer treatment. Concentrated HBC aqueous solution could transform into hydrogel within 30 s after injection under physiological temperature in non-chemical fashion. The properties of the HBC gels including chemical structure, surface morphology, and rheologic properties were studied. Gelation temperature and gelation time of HBC could be adjusted by HBC concentrations. The gel erosion rate in vivo was faster than solubilization rate in vitro. The mild inflammatory response caused by implantation of the hydrogel was acceptable. The DOX·HCl (1 mg/ml) loaded HBC gels displayed slow release rates that were independent of the HBC concentration, and significantly reduced viability of 4T-1 cells compared with the HBC gels after 1 day incubation. These results indicate that thermo-sensitive HBC hydrogels have promising potential as an injectable drug carrier for pharmaceutical applications.     

Investigation of charge effects on drug release behavior for ionic thermosensitive hydrogels

The influence of various drugs with different charges on the drug release behavior in porous ionic thermosensitive hydrogels was investigated. The present hydrogels were prepared from N-isopropylacrylamide (NIPAAm) and cationic monomer, trimethyl (acrylamido propyl) ammonium iodide (TMAAI), or anionic monomer, acrylic acid (AA), or zwitterionic monomer, N′,N′-dimethyl (acrylamido propyl) ammonium propane sulfonate (DMAAPS), or nonionic monomer, poly(ethylene glycol) methylether acrylate (PEGMEA), and pore-forming agent, poly(ethylene glycol) (PEG) with different molecular weights. Caffeine as a nonionic drug, crystal violet (CV) as a cationic drug solute, and phenol red as an anionic drug solute were chosen as model drugs to perform the drug release experiment. Results show that the release ratio of caffeine in the hydrogels is not affected by the ionicity of hydrogels. The CV strongly interacted with the anionic hydrogel; thus, the CV release ratio is very low. CV is only adsorbed on the skin layer of the cationic hydrogel due to charge repulsion and is released rapidly. The result of phenol red (anionic solute) release in the hydrogels is contrary to CV. In addition, the partition coefficients (K_d) and the drug delivery behavior of the present gels were also investigated.     

A comparative study of chitosan and poloxamer based thermosensitive hydrogel for the delivery of PEGylated melphalan conjugates

Abstract

Objective: Although the melphalan (ML) used extensively for the management of breast cancer, its clinical application is limited due to significant hemolytic activity. In the present work, a comparative analysis of two distinct in situ-based thermogelling polymers of PEGylated ML was performed.

Methods: Briefly, the PEGylated conjugate of the melphalan (MLPEG 5000) for local and sustained drug release action is loaded into two different thermogelling polymeric systems, namely chitosan- and poloxamer-based systems. The synthesized conjugate was loaded to a chitosan (MLP 5000) and poloxamer-based (MPX-CG) thermogelling injectable hydrogels. These thermogelling hydrogels were evaluated for in vitro hydrolysis, in vitro hemolytic activity. and in vitro anticancer activity.

Results: The lower percent cumulative hydrolysis was witness for both the hydrogels. MPX-CG and MLP 5000 hydrogels as predicted had shown lower percent cumulative hydrolysis of 3.31?±?0.1 and 1.67?±?0.1 after 6?h. The percentage hemolysis of MPX-CG and MLP 5000 even at a concentration of 32?µg/ml was found to be 39.23?±?1.24% and 34.23?±?2.24%, observed at 1?h, respectively. Both the hydrogels showed similar anticancer pattern, the MPX-CG hydrogel showed low cell viability of 8.4?±?1.1% at a concentration of 150?µM and the MLP-5000 hydrogel showed slight higher cell viability (13.12?±?5.4%) as compared with MPX-CG hydrogel.

Conclusion: Hence, from the present study it can be well understood that both the chitosan- and the poloxamer-based thermogelling hydrogel proves to be an effective drug delivery systems for the delivery of the PEGylated conjugates.     

Carboxymethyl derivative of scleroglucan: a novel thermosensitive hydrogel forming polysaccharide for drug delivery applications

A carboxymethyl derivative of scleroglucan (Scl-CM) with a derivatization degree of 65 ± 5% was synthesized. The rheological behaviour of this novel polymer was studied and compared with that of the starting polymer. We observed that the charged moieties carried on the chains could prevent the triple helix formation of Scl. Scl-CM aqueous solutions behave like true polymer solutions up to 1% w/v, whereas above this concentration a weak gel behaviour was observed. CaCl₂ addition to aqueous Scl-CM solutions led to a physical gel formation; the hydrogel strength was related to polymer and CaCl₂ concentrations. Temperature sweeps, registered at 1 Hz on hydrogels differing in CaCl₂ concentration, evidenced a gel → sol transition in the range of 30–40°C, depending on the molar ratio between carboxylic groups and Ca⁺². In order to verify a possible use of these hydrogels as drug delivery systems, acyclovir was loaded into the network. Rheological analysis evidenced that the loaded drug can affect the hydrogel elastic modulus. The release of acyclovir in phosphate buffer was evaluated at different temperatures in order to assess the suitability of this novel drug delivery system in topical applications.     

A novel pH-responsive hydrogel-based on calcium alginate engineered by the previous formation of polyelectrolyte complexes (PECs) intended to vaginal administration

This work aimed to develop a calcium alginate hydrogel as a pH responsive delivery system for polymyxin B (PMX) sustained-release through the vaginal route. Two samples of sodium alginate from different suppliers were characterized. The molecular weight and M/G ratio determined were, approximately, 107?KDa and 1.93 for alginate_S and 32?KDa and 1.36 for alginate_V. Polymer rheological investigations were further performed through the preparation of hydrogels. Alginate_V was selected for subsequent incorporation of PMX due to the acquisition of pseudoplastic viscous system able to acquiring a differential structure in simulated vaginal microenvironment (pH 4.5). The PMX-loaded hydrogel (hydrogel_PMX) was engineered based on polyelectrolyte complexes (PECs) formation between alginate and PMX followed by crosslinking with calcium chloride. This system exhibited a morphology with variable pore sizes, ranging from 100 to 200?μm and adequate syringeability. The hydrogel liquid uptake ability in an acid environment was minimized by the previous PECs formation. In vitro tests evidenced the hydrogels mucoadhesiveness. PMX release was pH-dependent and the system was able to sustain the release up to 6 days. A burst release was observed at pH 7.4 and drug release was driven by an anomalous transport, as determined by the Korsmeyer–Peppas model. At pH 4.5, drug release correlated with Weibull model and drug transport was driven by Fickian diffusion. The calcium alginate hydrogels engineered by the previous formation of PECs showed to be a promising platform for sustained release of cationic drugs through vaginal administration.     

An acryl resin-based swellable microneedles for controlled release intradermal delivery of granisetron

Swellable microneedles (SMNs) are made of hydrogels and can deliver drug with controlled delivery rate by the cross-link density of the hydrogel. In this study, an acryl resin-based SMNs was developed for poorly water-soluble drugs. The making process of the SMNs is very simple and only need 60?min. The SMNs has high mechanical strength and is not easily broken. In-vitro release of SMNs-loaded model drug, granisetron base (GRB), was investigated. The results showed that seven days controlled release of GRB was obtained when SMNs contained pore-foaming agents (1.5% dicalcium phosphate (CaHPO₄) and 1.5% polyvinylpyrrolidone (PVP)). The maximum amount delivered into skin was 86.158?±?7.82% of the initial GRB (2.1?mg) loaded on SMNs preparation. Pharmacokinetics study in rats indicated a dose-dependent profile of plasma GRB concentrations and that the controlled release of 2.1?mg dose was observed for 144?hours. In conclusion, these SMNs provided a potential minimally invasive route for controlled-release systemic delivery of poorly water-soluble drugs.     

A covalently crosslinked polysaccharide hydrogel for potential applications in drug delivery and tissue engineering

The development of non-cytotoxic hydrogels that can allow for the controlled release of molecules has important clinical and therapeutic applications. In this paper, we developed a series of in situ hydrogels by combining N,O-carboxymethyl chitosan and oxidized alginate without additional crosslinking agents. The rheological properties of these hydrogels as well as their gelling time, swelling ratio, and in vitro degradation behavior were investigated. We observed that although gelation was rapid at physiological temperature, it was even faster in the presence of higher oxidization degree of alginate. In vitro cytotoxicity study showed that the developed hydrogels were not cytotoxic after 24?h of culturing with NIH-3T3 cells. Additionally, bovine serum albumin was released from the hydrogels initially by diffusion at early stages followed by a degradation-dependent mechanism at later stages. In conclusion, the developed hydrogel might have potential application in the drug delivery system and tissue engineering.     

Albumin-crosslinked alginate hydrogels as sustained drug release carrier

To take advantage of the drug-binding ability of albumin as a component of drug delivery system, we have prepared hydrogels consisting of alginic acid (AL) and recombinant human serum albumin (rHSA) by dehydrating condensation using N-hydroxysuccininimide and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. As rHSA content increased, the swelling ratio of the hydrogel decreased, indicating rHSA functioned as a crosslinker. In fact, trypsin treatment solubilized the hydrogel. Salicylic acid, which has high affinity for rHSA, was loaded most on the hydrogel of the highest rHSA content despite the lowest swelling ratio. Meanwhile, drugs with less affinity for HSA such as o-anisic acid and benzoic acid were preferably loaded on the hydrogel having the highest swelling ratio but the lowest HSA content. The release of salicylic acid from the hydrogel sustained longer than o-anisic acid and benzoic acid, reflecting the affinity of the drug for HSA. Furthermore, the hydrogel could carry much of positively charged dibucaine by the interaction with anionic alginic acid and showed highly sustained release. Since the safety of AL and rHSA in medical use is guaranteed, rHSA-crosslinked AL hydrogel is expected to use as a sustained drug release carrier for drugs having affinity for HSA and those with cationic charge.     

Optoregulated Drug Release from an Engineered Living Material: Self‐Replenishing Drug Depots for Long‐Term,Light‐Regulated Delivery

On‐demand and long‐term delivery of drugs are common requirements in many therapeutic applications, not easy to be solved with available smart polymers for drug encapsulation. This work presents a fundamentally different concept to address such scenarios using a self‐replenishing and optogenetically controlled living material. It consists of a hydrogel containing an active endotoxin‐free Escherichia coli strain. The bacteria are metabolically and optogenetically engineered to secrete the antimicrobial and antitumoral drug deoxyviolacein in a light‐regulated manner. The permeable hydrogel matrix sustains a viable and functional bacterial population and permits diffusion and delivery of the synthesized drug to the surrounding medium at quantities regulated by light dose. Using a focused light beam, the site for synthesis and delivery of the drug can be freely defined. The living material is shown to maintain considerable levels of drug production and release for at least 42 days. These results prove the potential and flexibility that living materials containing engineered bacteria can offer for advanced therapeutic applications.     

Effects of crosslinking ratio,model drugs,and electric field strength on electrically controlled release for alginate-based hydrogel

The drug release characteristics of calcium alginate hydrogels, (Ca-Alg), under an electric field assisted transdermal drug delivery system were systematically investigated. The Ca-Alg hydrogels were prepared by the solution-casting using CaCl₂ as a crosslinking agent. The diffusion coefficients and the release mechanism of the anionic model drugs, benzoic acid and tannic acid, and a cationic model drug, folic acid on the Ca-Alg hydrogels were determined and investigated using a modified Franz-Diffusion cell in an MES buffer solution of pH 5.5, at a temperature of 37°C, for 48 h. The influences of the crosslinking ratio, —the mole of the crosslinking agent to the mole of the alginate monomer—mesh size, model drug size, drug charge, electric field strength, and electrode polarity were systematically studied. The drug diffusion coefficient decreased with an increasing crosslinking ratio and drug size for all of the model drugs. The drug diffusion coefficient is precisely controlled by an applied electric field and the electrode polarity depending on the drug charge, suitable for a tailor-made transdermal drug delivery system.     

Evaluation of Polyvinyl Alcohol Hydrogel as Sustained-Release Vehicle for Transdermal Sytem of Bunitrolol-HCL

In order to evaluate a bunitrolol (β-blocker preparation using poly(vinyl alchol) (PVA) hydrogel for hypertension as a transdermal delivery system, in vitro release characteristics and the permeation of bunitrolol through rat sking from hydrogel and the bunitrolol plasma profile after application onto abdominal skin in rats were examined. The PVA hydrogel containing bunitrolol-HCl was prepared by a low temperature crystallization method. The release of bunitrolol from PVA hydrogel followed with Ficklan diffusion (Higuchi model); the drug relaase, profile versus square root of relase. The release rate and premeation through rat skins of bunitrolol from hydrogels affected with preparation at various physical and chemical states. Longer freezing times, higher polymerization and higher concentration of PVA resulted in lower permeation. These results had relations with the results of release tests. Higher pH of preparation resulted in a higher permeation of bunitrolol, which did not have a relaion with the results of release tests. The plasma concentration of bunitrolol after application of hydrogel preparation onto the abdominal skins were relatively high at early times and sustained a plateau level during 48 h in rates. In conclusion, transdermal delivery system using PVA hydrogel is favorable with prolonged action for low available drugs such as bunitrolol-HCl.     

Synthesis and characterization of carboxymethyl chitosan hydrogel: Application as site specific delivery for lercanidipine hydrochloride

In the present study, carboxymethylchitosan (CMCS) was prepared from chitosan, crosslinked with glutaraldehyde and evaluated in vitro as a potential carrier for site specific drug delivery of lercanidipine hydrochloride (LERH). LERH was incorporated at the time of crosslinking of CMCS. The chitosan was evaluated for its degree of deacetylation (DD) and average molecular weight, which were found to be 84·6% and 3·5 × 10⁴ Da, respectively. The degree of substitution on prepared CMCS was found to be 0·68. All hydrogel formulations showed more than 86% and 77% yield and drug loading, respectively. The swelling behaviour of prepared hydrogels were checked in different pH values, 1·2, 6·8 and 7·4, indicated pH responsive swelling characteristic with very less swelling at pH 1·2 and quick swelling at pH 6·8 followed by linear swelling at pH 7·4 with slight increase. In vitro release profile was carried out at the same conditions as in swelling and drug release was found to be dependent on swelling of hydrogels and showed biphasic release pattern with non-fickian diffusion kinetics at higher pH. The carboxymethylation of chitosan, entrapment of drug and its interaction in prepared hydrogels were checked by FTIR, ¹H-NMR, DSC and p-XRD studies, which confirmed formation of CMCS from chitosan and absence of any significant chemical change in LERH after being entrapped in crosslinked hydrogel formulations. The surface morphology of formulation S6 was checked before and after dissolution, revealed open channel like pores formation after dissolution.     

In vitro release dynamics of model drugs from psyllium and acrylic acid based hydrogels for the use in colon specific drug delivery

Psyllium is medicinally important gel forming polysaccharides. Keeping in view, the pharmacological importance of psyllium and drug delivery devices based on hydrogels, psyllium, if suitably tailored to prepare the hydrogels, can act as the double potential candidates for the novel drug delivery systems. Therefore, it is an attempt to prepared psyllium and acrylic acid based pH sensitive novel hydrogels by using N,N'-methylenebisacrylamide (N,N-MBAAm) as crosslinker and ammonium persulfate (APS) as initiator for the use in colon specific drug delivery. The present paper discusses the swelling kinetics of the hydrogels and release dynamics of model drugs (tetracycline hydrochloride, insulin and tyrosine) from drug-loaded hydrogels, for the evaluation of the swelling mechanism and drug release mechanism from the polymeric networks .The effect of pH on the swelling kinetics and release pattern of drugs have been studied by varying the pH of the release medium. It has been observed that swelling and release of drugs from the hydrogels occurred through non-Fickian or anomalous diffusion mechanism in distilled water and pH 7.4 buffer. It shows that the rate of polymer chain relaxation and the rate of drug diffusion from these hydrogels are comparable.     

Recent advances in ocular drug delivery

Amongst the various routes of drug delivery, the field of ocular drug delivery is one of the most interesting and challenging endeavors facing the pharmaceutical scientist. Recent research has focused on the characteristic advantages and limitations of the various drug delivery systems, and further research will be required before the ideal system can be developed. Administration of drugs to the ocular region with conventional delivery systems leads to short contact time of the formulations on the epithelium and fast elimination of drugs. This transient residence time involves poor bioavailability of drugs which can be explained by the tear production, non-productive absorption and impermeability of corneal epithelium. Anatomy of the eye is shortly presented and is connected with ophthalmic delivery and bioavailability of drugs. In the present update on ocular dosage forms, chemical delivery systems such as prodrugs, the use of cyclodextrins to increase solubility of various drugs, the concept of penetration enhancers and other ocular drug delivery systems such as polymeric gels, bioadhesive hydrogels, in-situ forming gels with temperature-, pH-, or osmotically induced gelation, combination of polymers and colloidal systems such as liposomes, niosomes, cubosomes, microemulsions, nanoemulsions and nanoparticles are discussed. Novel ophthalmic delivery systems propose the use of many excipients to increase the viscosity or the bioadhesion of the product. New formulations like gels or colloidal systems have been tested with numerous active substances by in vitro and in vivo studies. Sustained drug release and increase in drug bioavailability have been obtained, offering the promise of innovation in drug delivery systems for ocular administration. Combining different properties of pharmaceutical formulations appears to offer a genuine synergy in bioavailability and sustained release. Promising results are obtained with colloidal systems which present very comfortable conditions of use and prolonged action.     

A casein-polysaccharide hybrid hydrogel cross-linked by transglutaminase for drug delivery

A protein-polysaccharide hydrogel was reported as a biocompatible, biodegradable, and non-toxic material that had biomedical applications such as drug delivery. The hydrogel, composed of 10% casein and 1% konjac glucomannan (KGM), was formed with 0.4 wt% transglutaminase (MTG) as the cross-linker. The physicochemical properties of the protein-polysaccharide hydrogel were investigated by SEM observation, FT-IR analysis, swelling ratio test, and stability test. The results of the stability test proved that the hydrogel with KGM had an obviously improved stability. Its degradation rate also decreased from 100% to less than 60% compared with the hydrogel without KGM at the end of the test. The results of the swelling ratio test demonstrated that the addition of KGM restricted the mobility of the chains, and decreased the swelling ratio of the hydrogel. The results of the FT-IR revealed hydrogen bond interactions during the gelation process upon the addition of KGM. To investigate in vitro release behavior, docetaxel was chosen as a model drug incorporated into the casein/KGM hydrogels. The hydrogel with 1% KGM exhibited a good drug release behavior.