Simultaneous determination of estramustine phosphate and its four metabolites in human plasma by liquid chromatography-ionspray mass spectrometry

A sensitive and selective method, using liquid chromatography-ionspray mass spectrometry, was developed and validated for the simultaneous determination of Estracyt (estramustine phosphate) and its four metabolites, estramustine, estromustine, estrone and estradiol, in human plasma. Deuterated internal standards were available for all analytes. The five compounds were extracted from plasma by protein precipitation with acetonitrile. The chromatographic separation was performed using a Zorbax SB C18, (150 x 4.6 mm i.d., 5 microm) reversed-phase column under gradient conditions with a mobile phase containing 2 mm ammonium acetate buffer (pH 6.8) and acetonitrile. MS detection was by electrospray ionization with multiple reaction monitoring in the positive ion mode for estramustine phosphate, estromustine and estramustine, and in the negative ion mode for estrone and estradiol. The limit of quantitation was 10 ng/mL for estramustine phosphate, 3 ng/mL for estromustine, estramustine and estrone and 30 ng/mL for estradiol. Linearity was verified from these LLOQs up to about 4000 ng/mL for the parent drug and 2000 ng/mL for the metabolites. Inter-day precision and accuracy values were all less than 15%. This assay was applied successfully to the routine analysis of human plasma samples collected in cancer patients administered estramustine phosphate intravenously.     

Drug release from hydrogel devices with ratecontrolling barriers

Zero order release of a drug from monolithic polymer devices fails because the drug concentration gradient within the matrix falls with time. In principle, it should be possible to maintain this concentration gradient constant via the introduction of a ratelimiting barrier to solute diffusion at the surface of the device. In this study, progesterone-dispersed monolithic devices were prepared from either polyhydroxyethyl methacrylate (HEMA) or a copolymer of HEMA and methoxyethoxyethyl methacrylate (MEEMA). These monolithic devices were soaked in an ethanol solution of ethylene glycol dimethacrylate (EGDMA) followed by exposure to UV light to create a crosslinked zone at the outer edge. The cross-linked zone has a much lower permeability to solute than the central region of the device and therefore serves as a rate-limiting barrier. Progesterone release studies demonstrated a zero order release from devices with the crosslinked outer layer. Drug release rates were dependent upon the UV treatment time, the EGDMA concentration, and the device soaking time in the EGDMA solution.     

Methotrexate polymer implant for the treatment of head and neck cancer

A biodegradable polymeric device releasing methotrexate (MTX) for the treatment of cancer of the head and neck was evaluated in vitro and in vivo. The polymer used for the preparation of the device was a copolyanhydride based on dimer erucic acid and sebacic acid loaded with 2–20% MTX. The drug was released constantly for about two weeks from small discs (1 × 3 mm) with complete degradation of the polymer when placed in phosphate buffer pH 7.4 at 37°C. The release and degradation rate was similar for all drug loading. MTX-loaded discs implanted subcutaneously in mice released the drug for about ten days with about 50% elimination of the device from the implantation site. The drug concentration was the highest in the tissue in contact with the device and decreased at distance from the device following a first order kinetics. The LD50 of MTX in polymer when implanted in mice was between 20 and 40 mg per kg. (1994)     

Transdermal drug transfer from a polymer device: study of the polymer and the process

Special polymer devices containing a drug are able to deliver the drug to the patient through transdermal delivery. Two points are of interest: the nature of the polymer device, and the process of drug delivery. The polymer device considered in this paper is able to maintain a constant drug concentration on the patient's skin surface. The process of drug delivery is studied through in vitro and in vivo tests. In vitro tests show that the skin plays the role of a membrane, with a steady state for the drug transfer following a non-steady state. The parameters of diffusion through the skin are thus calculated from this test. In vivo tests are described by a process of drug transfer consisting of two stages: the stages of absorption into, and elimination out of, the blood. The polymer device plays a major role, as it should maintain a constant concentration of drug on the skin.     

Tuning the release rate of acidic degradation products through macromolecular design of caprolactone-based copolymers

Macromolecular engineering is presented as a tool to control the degradation rate and release rate of acidic degradation products from biomedical polyester ethers. Three different caprolactone/1,5-dioxepan-2-one (CL/DXO) copolymers were synthesized: DXO/CL/DXO triblock, CL/DXO multiblock, and random cross-linked CL/DXO copolymer. The relation of CL and DXO units in all three copolymers was 60/40 mol %. The polymer discs were immersed in phosphate buffer solution at pH 7.4 and 37 degrees C for up to 364 days. After different time periods degradation products were extracted from the buffer solution and analyzed. In addition mass loss, water absorption, molecular weight changes, and changes in thermal properties were determined. The results show that the release rate of acidic degradation products, a possible cause of acidic microclimates and inflammatory responses, is controllable through macromolecular design, i.e., different distribution of the weak linkages in the copolymers.     

Development of implantable antitumor devices based on polyphosphazenes

Polyphosphazenes containing amino acid ester substituents are of considerable interest as bioerodible matrix systems for controlled release of drugs. In order to develop locally acting antitumor devices, a model anticancer agent, melphalan, was physically incorporated in three different polyphosphazene polymers. For studying the release rate of melphalan from the three polymers and the extent of degradation of melphalan during this sustained release process, a flow through-system was used. This system is characterized by low flow rates, in order to approximate the in vivo implantation situation. Eluents were used, with pH 7.0 and 5.0, showing a melphalan degradation half time (respectively 2.0 and 1.9 hours) comparable with those observed in vitro in human plasma. Polymer 1 (poly[bis(glycine ethyl ester)phosphazene]) released after one week 35% and 42% unhydrolyzed melphalan, at pH 7.0 and pH 5.0 respectively, in a gradual manner. Considerable lower release rates were observed using polymers 2 and 3. Polymer 2 (50% substituted with glutamic acid diethyl ester, 50% with glycine ethyl ester) showed release percentages of 10 and 14%, polymer 3 (50% substituted with phenylalanine ethyl ester, 50% with glycine ethyl ester) 12 and 14% after one week at pH 7.0 and 5.0, respectively. Melphalan concentrations were measured by applying a High Pressure Liquid Chromatography method with fluorescence detection. By this method also the two degradation products mono- and dihydroxy-melphalan could be measured. Considering the release profiles of these degradation products, the conclusion may be drawn that either melphalan is stabilized in the three polymers, or that melphalan is less exposed to the aqueous environment than is the case when used as a solution. These results justify expectations that it should be possible to develop locally acting tumor devices, being able to release an unstable anticancer agent in a gradual manner for several weeks or months and resulting in locally effective drug concentrations during this period.     

Drug release and biocompatibility of self‐assembled micelles prepared from poly (ɛ‐caprolactone/glycolide)‐poly (ethylene glycol) block copolymers

A series of poly(?‐caprolactone/glycolide)‐poly(ethylene glycol) (P(CL/GA)‐PEG) diblock copolymers were prepared by ring opening polymerization of a mixture of ?‐caprolactone and glycolide using mPEG as macro‐initiator and stannous octoate as catalyst. Self‐assembled micelles were prepared from the copolymers using nanoprecipitation method. The micelles were spherical in shape. The micelle size was larger for copolymers with longer PEG blocks. In contrast, the critical micelle concentration of copolymers increased with decreasing the overall hydrophobic block length. Drug loading and drug release studies were performed under in vitro conditions, using paclitaxel as a hydrophobic model drug. Higher drug loading was obtained for micelles with longer poly(ε‐caprolactone) blocks. Faster drug release was obtained for micelles of mPEG2000 initiated copolymers than those of mPEG5000 initiated ones. Higher GA content in the copolymers led to faster drug release. Moreover, drug release rate was enhanced in the presence of lipase from Pseudomonas sp., indicating that drug release is facilitated by copolymer degradation. The biocompatibility of copolymers was evaluated from hemolysis, dynamic clotting time, and plasma recalcification time tests, as well as MTT assay and agar diffusion test. Data showed that copolymer micelles present outstanding hemocompatibility and cytocompatibility, thus suggesting that P(CL/GA)‐PEG micelles are promising for prolonged release of hydrophobic drugs.     

Modulation of Tenoxicam release from hydrophilic matrix: modulator membrane versus rate-controlling membrane

This paper describes the preparation of two layered device comprising of tenoxicam containing layer and a drug free membrane layer based on Geomatrix Technology. Our device based on bilaminated films which produced by a casting/solvent evaporation technique. The drug-hydroxypropyl methylcellulose (HPMC) layer was covered by drug free membrane layer composed of a mixture of different ratios of HPMC and ethyl cellulose (EC). The prepared devices were evaluated for thickness, weight, drug content uniformity, water absorption capacity and in-vitro drug release. The films were also evaluated for appearance, smoothness and transparency. The influence of drug free membrane layer composition and thickness on the drug release pattern was studied on 12 devices (D1 to D12). The results indicate that, the release of drug from HPMC matrixes without the drug free membrane layer was fast and follows diffusion controlled mechanism. The release of drug from the devices D1, D4, D9 and D12 follow the same mechanism, while the release of drug from other devices become linear with time (zero order) and extended for long time especially when thickness and the ratio of EC was increased in the drug free membrane layer. From this study it is concluded that, changing the geometry of drug layer by addition of drug free membrane layer and changing its composition and thickness plays an important role in determining whether the drug free membrane layer is rate-controlling or modulator membrane. Hence it can facilitate the development of different pharmaceutical products with different release pattern.     

Fabrication of an ��-lipoic acid-eluting poly-(D,L-lactide-co-caprolactone) cuff for the inhibition of neointimal formation

The purpose of this study was to develop a novel polymer cuff for the local delivery of α-lipoic acid (ALA) to inhibit neointimal formation in vivo. The polymer cuff was fabricated by incorporating the ALA into poly-(_D,L-lactide-co-caprolactone) 40:60 (PLC), with or without methoxy polyethylene glycol (MethoxyPEG). The release kinetics of ALA and in vitro degradation by hydrolysis were analyzed by HPLC and field emission scanning electron microscopy (FE-SEM), respectively. In vivo evaluation of the effect of the ALA-containing polymer cuff was carried out using a rat femoral artery cuff injury model. At 24 h, 48% or 87% of the ALA was released from PCL cuffs with or without MethoxyPEG. FE-SEM results indicated that ALA was blended homogenously in the PLC with MethoxyPEG, whereas ALA was distributed on the surface of the PLC cuff without MethoxyPEG. The PLC cuff with MethoxyPEG showed prolonged and controlled release of ALA in PBS, in contrast to the PLC cuff without MethoxyPEG. Both ALA-containing polymer cuffs had a significant effect on the inhibition of neointimal formation in rat femoral artery. Novel ALA-containing polymer cuffs made of PLC were found to be biocompatible and effective in inhibiting neointimal formation in vivo. Polymer cuffs containing MethoxyPEG allowed the release of ALA for one additional week, and the rate of drug release from the PLC could be controlled by changing the composition of the polymer. These findings demonstrate that polymer cuffs may be an easy tool for the evaluation of anti-restenotic agents in animal models.     

hGH release from directly compressed hGH-PLGA biodegradable implantable tablets: Influence of physicomechanical factors

The incidence of compression conditions, porosity and polymer degradation on human growth hormone (hGH) release from PLGA implantable tablets was evaluated with the aim of gaining insight in the mechanism involved in drug delivery from biodegradable matrices. Tablets elaborated by direct compression of hGH with PLGA, applying various compression forces for different times, kept the integrity and the stability of the hormone. Tablet dimensions, viscoelastic properties, glass to rubber transition temperature (T_g), PLGA degradation rate and water uptake were analyzed in the freshly prepared implantable tablets as well as at several times during release test in phosphate buffer pH 7.4. Placebo tablets were also prepared to evaluate the incidence of hGH on the physicomechanical properties of the device and PLGA degradation rate. Porosity remarkably determined the amount of hGH released, through an effect on the easiness of water penetration in the tablet and on the beginning of PLGA degradation. The decrease in PLGA molecular weight during the first days in the release medium, despite of being minor, significantly conditioned hGH release rate. The more dramatic changes in PLGA molecular weight observed after 20 days in the release medium notably reduced the T_g and the viscous and elastic moduli of the tablets. The overall analysis of the events underwent by the tablets in contact with the aqueous medium was used to explain the drug release profile and may help to optimize the design of the PLGA-based implantable tablets as peptidic drug delivery systems.     

Design of a rate- and time-programming drug release device using a hydrogel: pulsatile drug release from kappa-carrageenan hydrogel device by surface erosion of the hydrogel

We have found that a repetitive pulsatile drug release with a certain time interval is observed from a monolithic hydrogel device by surface erosion of the hydrogel. As a model system of pulsatile drug release, dibucaine hydrochloride and kappa-carrageenan hydrogel were chosen as a drug and a device, respectively. Electrostatic interactions between dibucaine hydrochloride and kappa-carrageenan polymer segments are strong, since dibucaine hydrochloride is positively charged and each disaccharide repeating unit of kappa-carrageenan chains has one sulfate group. Dibucaine hydrochloride was loaded into the hydrogel by immersing dry kappa-carrageenan hydrogel disks in a dibucaine hydrochloride solution for 24 h. The pulsed release of dibucaine hydrochloride from the device was observed every 50 min between 30 and 250 min after the release starts. The weight of kappa-carrageenan hydrogel decreases in an oscillatory manner with time in distilled water. The oscillatory changes observed in the hydrogel weight in distilled water are considered to be caused by influx and efflux of water molecules into and from the surface and core of the hydrogel and by polymer liberation from the hydrogel. This phenomenon was well explained by our kinetic model [Colloids and Surfaces B 8 (1996) 93-100]. The time interval between pulses observed in drug release coincides with that observed in the oscillatory weight change of the hydrogel. From these, it was concluded that the pulsatile release of dibucaine hydrochloride from the device was caused by the pulsatile liberation of swollen kappa-carrageenan hydrogel from the surface of the device.     

Investigation of drug release and 1H‐NMR analysis of the in situ forming systems based on poly(lactide‐co‐glycolide)

In situ forming biodegradable polymeric systems loaded with betamethasone (BTM) and betamethasone acetate (BTMA) were prepared using poly(DL ‐lactide‐co‐glycolide) (PLGA), ethyl heptanoate (EH), and N‐methyl‐2‐pyrrolidone (NMP) as the biodegradable polymer, additive, and solvent, respectively. The drug release studies were carried out in buffer (pH = 7.4, 37°C) using high performance liquid chromatography (HPLC). ¹H‐NMR was used to determine the polymer degradation behavior, release mechanism, and interactions between the polymer and drug. The ¹H‐NMR spectra showed that all interactions between the polymer and drug were hydrogen bonding. Hydroxyl groups and fluorine in drugs were involved in hydrogen bonding with PLGA polymer. In ¹H‐NMR studies, we found that the degradation rate in the systems loaded with BTMA was higher than the systems loaded with BTM because BTMA is only slightly soluble and accelerates the hydrolysis of PLGA chains. The formulations loaded with BTM had obviously lower burst release compared with BTMA loaded samples. With respect to ¹H‐NMR spectra, the mechanism of BTM release is controlled by two effective factors: solvent removal and polymer degradation. Copyright © 2008 John Wiley & Sons, Ltd.     

Controlled delivery achieved with bi-layer matrix devices produced by co-injection moulding

The aim of this study was to design new soy protein-based bi-layered co-injection moulded matrix systems aimed to achieve controlled drug delivery. The devices consisted of a drug-free outer layer (skin) and a drug-containing core. The systems overcame the inherent disadvantage of non-linear release associated with diffusion-controlled single-layer matrix devices by providing additional releasing area with time to compensate for the decreasing release rate. As expected, the bi-layer devices presented a significant decrease in drug release rate when compared with a correspondent single layer matrix system. The skin thickness and the degree of crosslinking of the core appeared to be very important tools to tailor the release patterns. Furthermore, due to the amphoteric nature of the soy protein, the developed devices evidenced a pH-dependent behaviour. The mechanisms of drug release were also elucidated at two different pH values: i) pH 5.0, near the isoelectric point of soy (low matrix solubility); and ii) pH 7.4, physiological pH (high matrix solubility). Consequently, changing the release medium from pH 5.0 to pH 7.4 after two hours, led to an abrupt increase in drug release and the devices presented a typical controlled drug delivery profile: slow release/fast release. These evidences may provide for the development of individual systems with different release onsets that in combination may exhibit drug releases at predetermined times in a pre-programmed way. Another possibility is the production of three-layer devices presenting bimodal release profiles (fast release/slow release/fast release) by similar technologies. Scanning electron micrograph of a developed bi-layer device.     

Three-dimensional porous HPMA-co-DMAEM hydrogels for biomedical application

The aim of this work is to develop a novel biocompatible drug delivery carrier and tissue engineering scaffold with the ability of controlled drug release and also tissue regeneration. We have synthesized N-(2-hydroxypropyl)methacrylamide and 2-(dimethylamino)ethyl methacrylate copolymer-based hydrogels loaded with doxorubicin and tested in vitro. The manifestation of temperature sensitivity is noted with a sharp decrease or increase in hydrogel optical transparency that happens with the temperature exceeding a critical transition value. The drug release profile exhibited pH-sensitive behavior of the hydrogel. The hydrolytic degradation of gel and in vitro studies of polymer–doxorubicin conjugate and doxorubicin release from hydrogel matrix indicated that hydrogels were stable under acidic conditions (in buffers at pH 4.64 and 6.65). In both drug forms, polymer–doxorubicin conjugate and free doxorubicin could be released from the hydrogel scaffold at a rate depending directly on either the rate of drug diffusion from the hydrogel or rate of hydrogel degradation or at rate controlled by a combination of the both processes. In vitro analysis showed homogenous cell attachment and proliferation on synthesized hydrogel matrix. In vivo implantation demonstrated integration of the gel with the surrounding tissue of mice within 2 weeks and prominent neo-angiogenesis observed in the following weeks. This multifunctional hydrogels can easily overcome biological hurdles in the in vivo conditions where the pH range changes drastically and could attain higher site-specific drug delivery improving the efficacy of the treatment in various therapeutical applications, especially in cancer therapy, and could also be used as tissue engineering scaffold due to its porous interconnected and biocompatible behavior.     

Poly(D,L-lactide-co-glycolide)/hydroxyapatite core-shell nanosphere. Part 2: Simultaneous release of a drug and a prodrug (clindamycin and clindamycin phosphate)

The novel concept of a simultaneous, controlled release of a drug and a prodrug with different physico-chemical properties was applied in order to prolong the release period of antibiotics and estimate their high local concentrations, which are the necessary preconditions for the treatment of some chronic infection diseases. For this purpose poly(D,L-lactide-co-glycolide)/hydroxyapatite (PLGA/HAp) core-shell nanostructures were used as the carrier of clindamycin-base, as a drug, and clindamycin-2-phosphate, as a prodrug model. As a result, a two-step release was observed: the controlled release of the more soluble phosphate form and the sustained release of the less-soluble base form of clindamycin, resulting in a high overall concentration of the released drug during the period of 30 days in vitro. The HAp phase within the PLGA core-shells, applied as a drug carrier, delayed the process of the degradation of the polymer; however, the presence of the drug affected the process of degradation and this influence was the dominant factor in the control over the degradation of the polymer phase of PLGA/HAp and the consequent kinetics of the drug release.     

聚环氧乙烷-g-聚己内酯两亲性接枝共聚物的合成及药物释放行为

通过环氧丙醇(GL)与环氧乙烷(EO)的阴离子顺序开环聚合制备了水溶性嵌段共聚物PEO-b-PGL, 以PGL嵌段每个重复单元的侧羟基为引发点进一步引发ε-己内酯(CL)的开环聚合, 合成了结构规整的以聚环氧乙烷(PEO)为主链的两亲性接枝共聚物(PEO-b-PGL-g-PCL). 研究了PEO-b-PGL-g-PCL在水相中的自组装行为, 采用稳态荧光探针法测定了胶束的临界胶束浓度(cmc). 以疏水性药物阿霉素(DOX)为模型药物, 研究了两亲性接枝共聚物的化学组成对药物的扩散释放以及降解释放行为的影响.     

Temperature- and pH-responsive star amphiphilic block copolymer prepared by a combining strategy of ring-opening polymerization and reversible addition-fragmentation transfer polymerization

The star-shaped poly(ε-caprolactone)-b-poly(2-(dimethylamino)ethyl methacrylate) (HPs-Star-PCL-b-PDMAEMA) was synthesized by ring-opening polymerization and reversible addition-fragmentation chain transfer (RAFT) polymerization. Star-shaped polycaprolactones (HPs-Star-PCL) were synthesized by the bulk polymerization of ε-caprolactone (CL) with a hyperbranched polyester initiator and tin 2-ethylhexanoate as a catalyst. The number-average molecular weight of these polymers linearly increased with the increase of the molar ratio of CL to hyperbranched initiator. HPs-Star-PCL was converted into a HPs-star-PCL-RAFT by an esterification of HPs-Star-PCL and 4-cyanopentanoic acid dithiobenzoate. Star amphiphilic block copolymer HPs-Star-PCL-b-PDMAEMA was obtained via RAFT polymerization of 2-(dimethylamino)ethyl methacrylate (DMAEMA). The molecular weight distribution of HPs-Star-PCL-b-PDMAEMA was narrow. Furthermore, the micellar properties of HPs-Star-PCL-b-PDMAEMA in water were studied at various temperatures and pH values by means of dynamic light scattering (DLS). The results indicated that the star copolymers had the pH- and temperature-responsive properties. The release behaviors of model drug aspirin from the star polymer indicated that the rate of drug release could be effectively controlled by pH value and temperature.     

Phototriggered release of photolabile drugs via two-photon absorption-induced cleavage of polymer-bound dicoumarin

7-(tert-Butyldimethylsiloxy)-7′-(methacryloxy)dicoumarin (TBS-Cum-D -MA) is introduced as a versatile polymerizable and photocleavable linker system for drug attachment to acrylic polymers. Following the copolymerization of the TBS-Cum-D -MA with monomeric methylmethacrylate, a model drug chlorambucil was attached in a simple reaction. Phototriggered drug release via single- and two-photon absorption induced cycloreversion of the cyclobutane of the dicoumarin part was investigated. The bound drug chlorambucil is sensitive to UV light being required for single-photon induced cleavage of the dicoumarin linker and decomposes upon UV exposure. However, under the conditions of two-photon absorption induced drug release, no photodegradation of chlorambucil was observed. As the only effective two-photon absorber in the molecule is the cyclobutane structure, even high energies of visible light do not cause any degradation of the drug. This suggests that two-photon-triggered drug release may be successfully accomplished even with UV light sensitive drugs. The concept introduced here may be a powerful strategy in polymer design for photocontrolled drug delivery devices. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2443–2452, 2007     

Design of a rate- and time-programming drug release device using a hydrogel: pulsatile drug release from κ-carrageenan hydrogel device by surface erosion of the hydrogel

We have found that a repetitive pulsatile drug release with a certain time interval is observed from a monolithic hydrogel device by surface erosion of the hydrogel. As a model system of pulsatile drug release, dibucaine hydrochloride and κ-carrageenan hydrogel were chosen as a drug and a device, respectively. Electrostatic interactions between dibucaine hydrochloride and κ-carrageenan polymer segments are strong, since dibucaine hydrochloride is positively charged and each disaccharide repeating unit of κ-carrageenan chains has one sulfate group. Dibucaine hydrochloride was loaded into the hydrogel by immersing dry κ-carrageenan hydrogel disks in a dibucaine hydrochloride solution for 24 h. The pulsed release of dibucaine hydrochloride from the device was observed every 50 min between 30 and 250 min after the release starts. The weight of κ-carrageenan hydrogel decreases in an oscillatory manner with time in distilled water. The oscillatory changes observed in the hydrogel weight in distilled water are considered to be caused by influx and efflux of water molecules into and from the surface and core of the hydrogel and by polymer liberation from the hydrogel. This phenomenon was well explained by our kinetic model [Colloids and Surfaces B 8 (1996) 93–100]. The time interval between pulses observed in drug release coincides with that observed in the oscillatory weight change of the hydrogel. From these, it was concluded that the pulsatile release of dibucaine hydrochloride from the device was caused by the pulsatile liberation of swollen κ-carrageenan hydrogel from the surface of the device.     

Dendritic polymers based on poly(ethylene glycol) -co- poly(glycolic acid) -co- methacrylate and 2.0 G -polyamidoamine- metharylamide: Design, characterization, and in vitro degradation, and drug release properties

In this paper, the properties of the complete degradation process of newly synthesized multi-block 2.0 G-polyamidoamine-double bond (PAMAM-DB) and resoluble poly (ethylene glycol) -co- poly (glycolic acid) -co- methacryloyl chloride (PEG-co-PGA-co-DB, 4KG5-DB) macromonomers were reported. Rectangular shaped samples were prepared by crosslinking the components using both chemical and photo initiators and exposure to UV light. The aims of the study were to examine the effects of the vitro degradation and drug delivery of the crosslinking group on the properties of photocrosslinked hydrogels. The experimental variable was PAMAM-DB: 4KG5-DB ratio. The effects of this variable on local PH, water uptake, mass loss, and drug release were explored. Polymers were characterized by ¹H NMR, ¹³C NMR, FT-IR, and SEM. Our study revealed that polymers with 40%, 50%, 60% 4KG5-DB (mass fraction) showed more excellent mechanical properties, 40% also showed outstanding vitro degradation properties. In vitro drug release, however, 60% drug released mechanism seemed to approach the Fickian diffusion and possessed more excellent drug release properties compared with formulation 40% and 50%. In general, an increase ratio of 4KG5-DB led to a higher density of tree-like polymer which resulted in slower of degradation and drug release. Incorporation of 4KG5-DB into the polymer was critical for maintaining integrity and increasing hydrophilicity during degradation. These results obtained suggest that this system could be potential as a material for bone replacement and controlled delivery of drugs.