Hollow,pH‐sensitive calcium–alginate/poly(acrylic acid) hydrogel beads as drug carriers for vancomycin release

In this study, hollow calcium–alginate/poly(acrylic acid) (PAA) hydrogel beads were prepared by UV polymerization for use as drug carriers. The hollow structure of the beads was fortified by the incorporation of PAA. The beads exhibited different swelling ratios when immersed in media at different pH values; this demonstrated that the prepared hydrogel beads were pH sensitive. A small amount (<9%) of vancomycin that had been incorporated into the beads was released in simulated gastric fluid, whereas a large amount (≤67%) was released in a sustained manner in simulated intestinal fluid. The observed drug‐release profiles demonstrated that the prepared hydrogel beads are ideal candidate carriers for vancomycin delivery into the gastrointestinal tract. Furthermore, the biological response of cells to these hydrogel beads indicated that they exhibited good biological safety and may have additional applications in tissue engineering. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Thermoresponsive/low‐fouling Zwitterionic hydrogel for controlled drug release

A controlled/ living free‐radical polymerization technique was introduced to prepared a homogeneous poly(N‐isopropylacrylamide)‐g‐poly(sulfobetaine methacrylate) hydrogel (RG) possessing a highly porous architecture via two steps. Compared to a poly(N‐isopropylacrylamide)‐co‐poly(sulfobetaine methacrylate) hydrogel (CG) prepared by conventional radical polymerization, RG exhibited a much faster shrinking rate (it lost over 72% of the water in 15 min) in response to the temperature changes. The release behaviors of tetracycline hydrochloride (TCHC) of the hydrogels indicated the TCHC release from the RG could be prolonged to 48 h at 37°C; this was much longer than that for CG (5 h at 37°C). Bovine serum albumin (BSA) was chosen as the model protein to examine the low‐fouling properties of the RG. The BSA adsorption data showed that improved antifouling properties could be achieved by the RG at both 25 and 37°C. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39816.     

Dual responsive polymeric bionanocomposite gel beads for controlled drug release systems

Scientists are searching potential solutions for cancer treatments as well as ways to avoid the side effects of anti‐cancer agents, via targeted drug delivery. The aim of this research is to propose dual responsive beads based on sodium alginate (SA), methylcellulose (MC), and magnetic iron oxide nanoparticles (MIONs) for controlled release of 5‐Fluorouracil (5‐FU) as model drug. The beads were prepared by the dual crosslinking of SA and MC in the presence of MIONs. The structural, thermal, morphological, magnetic characteristics as well as the release profile of 5‐FU were studied. The characterization results showed that the drug molecules and MIONs were well dispersed in the polymeric matrix. The cumulative release percentage was ca. 80% at pH = 4.2 and 40% at pH = 7.2 after 6 h. Thus, the sensitivity of beads on the pH value was verified. Moreover, the release profile exhibited reduction with an increase in the concentration of MIONs under an external magnetic field. The obtained results confirmed the dual sensitive release of 5‐FU (i.e., PH/magnetic) that can be used for the targeted and controlled drug delivery systems. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 45143.     

Development of pH‐sensitive nanogels for cancer treatment using crosslinked poly(aspartic acid‐graft‐imidazole)‐block‐poly(ethylene glycol)

pH‐sensitive nanogels (NGs) based on poly(aspartic acid‐graft‐imidazole)‐poly(ethylene glycol) were developed using linear PEG with different molecular weights (2000 and 4000 Da) as crosslinkers. The pH‐sensitive NGs showed reversible size changes during continuously alternating pH changes. The anticancer treatment potential of pH‐sensitive NGs was studied using a model drug, irinotecan (IRI). IRI‐loaded NGs (ILNs) showed different drug release kinetics in acidic versus neutral pH, in addition to pH‐dependent cytotoxicity. Due to its longer crosslinker, ILN 4 (crosslinked with PEG 4000) showed faster IRI release and a greater magnitude of IRI release than ILN 2 (crosslinked with PEG 2000), resulting in greater cytotoxicity against HCT 116 colorectal cancer cells. These pH‐sensitive NGs could potentially be used in cancer treatment by mediating the accumulation and release of IRI from ILNs in the acidic tumor environment and by reducing systemic toxicity due to reversible swelling–shrinkage. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46268.     

Poly(N‐isopropylacrylamide) hydrogel: Effect of hydrophilicity on controlled release of ibuprofen at different pH

Stimuli‐sensitive drug delivery systems (DDSs) have attracted considerable attention in medical and pharmaceutical fields; thermo‐sensitive DDS dealing with poly(N‐isopropylacrylamide) (PNIPAM) have been widely studied. Hydrogels composed of temperature‐sensitive NIPAM and biocompatible and pH‐sensitive maleic acid (MAc) were synthesized by sedimentation polymerization. Experiments on drug release from the crosslinked NIPAM‐co‐MAc hydrogel loaded with ibuprofen into different pH buffer solutions were successfully carried out at temperature swing between 25 and 40°C. The in vitro release studies have showed that the release rate depended on acidity or basicity (polarity) of the medium and the gel and swelling ratio of the gel network as a function of the environmental pH and temperature. The SEM image of the dry bead gave more insight into the surface architecture and the thermal studies shine light on the decomposition pattern and glass transition temperature of the gel. The mechanism of the drug release was discussed in relation to the diffusion rate and the abrupt change in the pH of the medium. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Self-assembled poly(ethylene glycol) methyl ether-grafted gelatin nanogels for efficient delivery of curcumin in cancer treatment

Curcumin (CUR) is a natural active ingredient that attracted much attention for its chemotherapeutic activity against tumors without causing toxicity in healthy cells. However, it has certain limitations for being used in chemotherapy such as low aqueous solubility and hydrolytic instability in the physiological environment. In this study, self-assembled poly(ethylene glycol) methyl ether-grafted gelatin (Gel-mPEG) nanogels were fabricated as delivery systems to improve the applicability of CUR in cancer treatment. CUR-loaded Gel-mPEG nanogels exhibited desired size range, relatively colloidal stability, and provided enhanced CUR stability in aqueous solutions. Especially, they showed significant high CUR loading capacity and better anticancer activity than free CUR as compared to previously reported CUR-loaded nanogels according to the best of our knowledge. Moreover, the in vitro release of CUR from the nanogels was controlled and prolonged up to 96 h. These results demonstrated that Gel-mPEG nanogels are the promising modality for the efficient delivery of CUR in cancer treatment. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019 , 136, 47544.     

Independent control of lower critical solution temperature and swelling behavior with pH for poly(N‐isopropylacrylamide‐co‐maleic acid)

Polymer solutions that gel in response to changes in temperature and pH are of interest for various forms of drug delivery, and it is desirable to increase swelling for diffusion‐controlled release without bringing the lower critical solution temperature (LCST) above 37°C. N‐isopropylacrylamide (NIP) was polymerized with maleic acid (MAc), a diprotic acid, and acrylic acid (AAc), a monoprotic acid, to compare swelling and temperature response with changes in pH. For samples with equal acid contents and almost identical LCST responses to pH, poly(N‐isopropylacrylamide‐co‐maleic acid) (pNIP MAc) demonstrated greater swelling than poly(N‐isopropylacrylamide‐co‐acrylic acid) (pNIP AAc). The LCST increase for MAc occurred at a pH corresponding to the deprotonation of almost all of the first acid groups. Further increases in pH led to the deprotonation of the second ? COOH and only served to increase the charge concentration at a given location. These results provide strong support for the theory that LCST results largely from uninterrupted chain lengths of NIP and that swelling results from the actual charge density of acid groups along the chain. Because the use of a diprotic acid copolymer allows swelling to be decoupled from LCST, pNIP MAc may be an appropriate candidate for pH‐sensitive drug‐delivery applications. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2110–2116, 2004     

Sustained release behavior of pH‐responsive poly(vinyl alcohol)/poly(acrylic acid) hydrogels containing activated carbon fibers

The composites of pH‐responsive poly(vinyl alcohol)/poly(acrylic acid) hydrogel and activated carbon fibers (ACFs) were prepared as sustained drug release system with excellent mechanical properties. The mechanical properties of hydrogels were improved greatly by addition of ACFs. The thinner ACFs were more effective in increasing the mechanical properties of composite hydrogels. The cumulative amount of release and the release period were dependent on the surface area and the pore volume of ACFs. The drug release was maximized at basic condition due to the pH‐sensitive hydrogel matrices and the initial bust phenomenon was alleviated by incorporating ACFs in the hydrogels. The drug release was sustained about four times longer and the mechanical property was increased about 2.6 times higher because ACFs worked as drug reservoir and reinforcement. Cytotoxicity evaluation confirmed the biocompatible characteristics of the ACFs‐containing hydrogels. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Kinetics study of isothermal nicotine release from poly(acrylic acid) hydrogel

The isothermal kinetic of the release of nicotine from a poly(acrylic acid) (PAA) hydrogel was investigated at temperature range from 26°C to 45°C. Specific shape parameters of the kinetic curves, the period of linearity and saturation time were determined. The change in the specific shape parameters of the kinetic curves with temperature and the kinetic parameters of release of nicotine E_a and ln A were determined. By applying the “model fitting” method it was established that the kinetic model of release of nicotine from the PAA hydrogel was [1 − (1 − α)^1/3] = k_Mt. The limiting stage of the kinetics release of nicotine was found to be the contracting volume of the interaction interface. The distribution function of the activation energy was determined and the most probable values of activation energies of 25.5 kJ mol⁻¹ and 35 kJ mol⁻¹ were obtained. Energetically heterogeneity of the interaction interface was explained by the existence of the two different modes of bonding the nicotine molecules onto the hydrogel network by hydrogen bond and electrostatic forces. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Epoxidized poly(N‐isopropyl acrylamide)‐b‐epoHTPB‐b‐poly(N‐isopropyl acrylamide) triblock copolymer micelle nanoparticles for 10‐hydroxycamptothecin drug release

Thermoresponsive poly(N‐isopropyl acrylamide) (PNIPAM)‐block‐hydroxy‐terminated polybutadine‐block‐PNIPAM triblock copolymers were synthesized by atom transfer radical polymerization; this was followed by the in situ epoxidation reaction of peracetic acid. The copolymers were characterized by ¹H‐NMR, Fourier transform infrared spectroscopy, and size exclusion chromatography measurements, and their physicochemical properties in aqueous solution were investigated by surface tension measurement, fluorescent spectrometry, ultraviolet–visible transmittance, transmission electron microscopy observations, dynamic light scattering, and so on. The experimental results indicate that the epoxidized copolymer micelle aggregates retained a spherical core–shell micelle structure similar to the control sample. However, they possessed a decreased critical aggregate concentration (CAC), increased hydrodynamic diameters, and a high aggregation number and cloud point because of the incorporation of epoxy groups and so on. In particular, the epoxidized copolymer micelles assumed an improved loading capacity and entrapment efficiency of the drug, a preferable drug‐release profiles without an initial burst release, and a low cytotoxicity. Therefore, they were more suitable for the loading and delivery of the hydrophobic drug as a controlled release drug carrier. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41877.     

Dual‐stimuli‐responsive polymer‐coated mesoporous silica nanoparticles used for controlled drug delivery

In this article, a temperature‐ and pH‐responsive delivery system based on block‐copolymer‐capped mesoporous silica nanoparticles (MSNs) is presented. A poly[2‐(diethylamino)ethyl methacrylate)] (PDEAEMA)‐b‐poly(N‐isopropyl acrylamide) (PNIPAM) shell on MSNs was obtained through the surface‐initiated atom transfer radical polymerization. The block copolymer PDEAEMA‐b‐PNIPAM showed both temperature‐ and pH‐responsive properties. The release of the loaded model molecules from PDEAEMA‐b‐PNIPAM‐coated MSNs could be controlled by changes in the temperature or pH value of the medium. The as‐desired drug‐delivery carrier may be applied to biological systems in the future. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42395.     

Biocompatible and biodegradable alginate/poly(N‐isopropylacrylamide) hydrogels for sustained theophylline release

Mixed‐interpenetrated polymeric networks based on sodium alginate (ALG) and poly(N‐isopropylacryl amide) (PNIPAAm) covalently cross‐linked with N,N'‐methylenebisacrylamide are studied for their biocompatibility, nontoxicity, and biodegradability aiming their application in drug delivery. The presence of drug‐polymeric matrix interactions and the distribution of the drug in the polymeric network for theophylline‐loaded ALG/PNIPAAm hydrogels are also investigated by spectroscopic and microscopic methods. The quantitative evaluation of theophylline loaded hydrogels performed by NIR‐CI technique shows a better drug entrapment and a higher homogeneity of the samples with increased alginate content. The thermal behavior of the hydrogels is significantly modified by theophylline presence. The application of the ALG/PNIPAAm hydrogels as carriers for sustained drug release formulations was assessed by the theophylline release tests performed both by in vitro and in vivo studies. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40733.     

Poly(methyl methacrylate)/poly(ethylene glycol)/poly(ethylene glycol dimethacrylate) micelles: Preparation,characterization, and application as doxorubicin carriers

A crosslinked amphiphilic copolymer [poly(ethylene glycol) (PEG)–poly(methyl methacrylate) (PMMA)–ethylene glycol dimethacrylate (EGDM)] composed of PMMA, PEG, and crosslinking units (EGDM) was synthesized by atom transfer radical polymerization to develop micelles as carriers for hydrophobic drugs. By adjusting the molar ratio of methyl methacrylate and EGDM, three block copolymer samples (P0, P1, and P2) were prepared. The measurement of gel permeation chromatography and ¹H‐NMR indicated the formation of crosslinked structures for P1 and P2. Fluorescence spectroscopy measurement indicated that PEG–PMMA–EGDM could self‐assemble to form micelles, and the critical micelle concentration values of the crosslinked polymer were lower than those of linear ones. The prepared PEG–PMMA–EGDM micelles were used to load doxorubicin (DOX). The drug‐loading efficiencies of P1 and P2 were higher than that of P0 because the crosslinking units enhanced the micelles' stability. With increasing drug‐loading contents, DOX release from the micelles in vitro was decreased, and in the crosslinked formulations, the release rate was also slower. An in vitro release study indicated that DOX release from the micelles for the linear samples was faster than that for crosslinked micelles. The drug feeding amount increased and resulted in an increase in the drug‐loading content, and the loading efficiency decreased. These PEG–PMMA–EGDM micelles did not show toxicity in vitro and could reduce the cytotoxicity of DOX in the micelles; this suggested that they are good candidates as stable drug carriers. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39623.     

Biomineralized hyaluronic acid/poly(vinylphosphonic acid) hydrogel for bone tissue regeneration

Novel biomineralized hydrogels composed of hyaluronic acid (HA) and vinyl phosphonic acid (VPAc) were designed with the aim of developing a biomimetic hydrogel system to improve bone regeneration by local delivery of a protein drug including bone morphogenetic proteins. We synthesized crosslinked hydrogels composed of methacrylated HA and poly(VPAc) [P(VPAc)], which serves as a binding site for calcium ions during the mineralization process. The HA/P(VPAc) hydrogels were biomineralized by a urea‐mediation method to create functional polymer hydrogels that can deliver the protein drug and mimic the bone extracellular matrix. The water content of the hydrogels was influenced by the HA/P(VPAc) composition, crosslinking density, biomineralization, and ionic strength of the swelling media. All HA/P(VPAc) hydrogels maintained more than 84% water content. Enzymatic degradation of HA/P(VPAc) hydrogels was dependent on the concentration of hyaluronidase and the crosslinking density of the polymer network within the hydrogel. In addition, the release behavior of bovine serum albumin from the HA/PVPAc hydrogels was mainly influenced by the drug loading content, water content, and biomineralization of the hydrogels. In a cytotoxicity study, the HA/P(VPAc) and biomineralized HA/P(VPAc) hydrogels did not significantly affect cell viability. These results suggest that biomineralized HA/P(VPAc) hydrogels can be tailored to create a biomimetic hydrogel system that promotes bone tissue repair and regeneration by local delivery of protein drugs. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41194.     

Thermosensitive poly(n‐isopropylacrylamide) hydrogels bonded on cellulose supports

A two‐step initiation and polymerization process was developed for the preparation of two series of hydrogel–cellulose composites with distinctively different morphologies and swelling behaviors. Hydroentangled cotton cellulose fibers were optimally initiated in 20 mM aqueous ammonium cerium(IV) nitrate for 15 min and then polymerized in aqueous solutions of N‐isopropylacrylamide (NIPAAm) monomer and N,N′‐methylene bisacrylamide (BisA) crosslinker. The extents of hydrogels on the cellulose solids could be controlled by variations in the concentrations of the monomer and crosslinker as well as the NIPAAm/BisA solution‐to‐solid ratios. The two series of hydrogel–cellulose composites formed were hydrogel‐covered/filled cellulose (I) and cellulose‐reinforced hydrogel (II) composites. Series I composites were synthesized with NIPAAm/BisA solutions below the liquid saturation level of the cellulose; this led to pore structures (size and porosity) that depended on both the extent and swelling of the grafted hydrogels. Series II composites were polymerized in the presence of excessive NIPAAm/BisA solutions to produce cellulose solids completely encapsulated in the hydrogels. All the cellulose‐supported hydrogels exhibited lower extents of phase transition over a wider temperature range (28–40°C) than the free poly(N‐isopropylacrylamide) hydrogels (32°C). These findings demonstrate that hydrogels can be used to control the pore structure of cellulose and can be supported with cellulose fibers. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 89: 999–1006, 2003     

Preparation and characterization of thermo‐sensitive poly(vinyl alcohol)‐based hydrogel as drug carrier

Poly(vinyl alcohol)s (PVA) with high and low molecular weights were chemically modified by introducing acetaldehyde onto the polymer backbone to induce thermal‐responsive properties. The influence of both molecular weight ( ) and acetalization degree on the lower critical solution temperature (LCST) of thermo‐sensitive polymer was investigated. Moreover, a temperature responsive hydrogel was prepared by controlled cross‐linking of acetalized poly(vinyl alcohol) (APVA) and glutaraldehyde. As a model drug, ciprofloxacin was introduced into the prepared thermal sensitive hydrogel to reveal the drug loading and release behaviors. The structure, thermo‐sensitivity, swelling/deswelling kinetics, morphology, and drug loading/release behaviors were also investigated. The results indicated that the APVA polymer solution exhibited temperature responsivity, and APVA with high acetalization degree showed low LCST, whereas those with high PVAs showed high LCST. Meanwhile, morphology study was identical with the swelling/de‐swelling behavior. The loading and release of ciprofloxacin were controllable. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39720.     

Fabrication of thermoresponsive,core‐crosslinked micelles based on poly[N‐isopropyl acrylamide‐co‐3‐(trimethoxysilyl)propylmethacrylate]‐b‐poly{N‐[3‐(dimethylamino)propyl]methacrylamide} for the codelivery of doxorubicin and nucleic acid

Thermoresponsive amphiphilic copolymer, poly[N‐isopropyl acrylamide‐co‐3‐(trimethoxysilyl)propylmethacrylate]‐b‐poly{N‐[3‐(dimethylamino)propyl]methacrylamide} with a branched structure was designed and synthesized by consecutive reversible addition–fragmentation chain‐transfer polymerization. The further hydrolysis of trimethoxysilyl functions in 3‐(trimethoxysilyl) propyl methacrylate units led to the fabrication of core‐crosslinked (CCL) micelles with silica crosslinks at temperatures above the lower critical solution temperature of the poly(N‐isopropyl acrylamide) block. The thermally induced structural and morphological changes of the CCL micelles in aqueous solution were investigated by transmission electron microscopy and ¹H‐NMR analyses. The resulting CCL micelles were further explored as nanocarriers for the codelivery of an anticancer drug and nucleic acid for enhanced therapeutic efficacy. The CCL micelles effectively condensed the nucleic acid and mediated higher gene transfer in the presence of serum than in serum‐free transduction. A cytotoxicity study revealed that whereas the pure CCL micelles exhibited unapparent cytotoxicity, the codelivery of p53 and doxorubicin with the CCL micelle formulation resulted in better treatment efficiency than sole chemotherapy. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41752.     

Poly(N‐isopropylacrylamide‐co‐poly(ethylene glycol))‐acrylate simultaneously physically and chemically gelling polymer systems

In an effort to create an in situ physically and chemically cross‐linked hydrogel for in vivo applications, N‐isopropylacrylamide (NIPAAm) was copolymerized with poly(ethylene glycol)‐monoacrylate (PEG‐monoacrylate) and then the hydroxyl terminus of the PEG was further modified with acryloyl chloride to form poly(NIPAAm‐co‐PEG) with acrylate terminated pendant groups. In addition to physically gelling with temperature changes, when mixed with a multi‐thiol compound such as pentaerythritol tetrakis 3‐mercaptopropionate (QT) in phosphate buffer saline solution of pH 7.4, this polymer formed a chemical gel via a Michael‐type addition reaction. The chemical gelation time of the polymer was affected by mixing time; swelling of the copolymer solutions was temperature dependant. Because of its unique gelation properties, this material may be better suited for long‐term functional replacement applications than other thermo‐sensitive physical gels. Also, the PEG content of this material may render it more biocompatible than similar HEMA‐based precursors in previous simultaneous chemically and physically gelling materials. With its improved mechanical strength and biocompatibility, this material could potentially be applied as a thermally gelling injectable biomaterial for aneurysm or arteriovenous malformation (AVM) occlusion. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Synthesis and In vitro cytotoxicity of poly(ethylene glycol)–epothilone B conjugates

Natural epothilone B (EPOB) is currently in clinical trials for treatment of advanced cancers. In this study, two poly(ethylene glycol) (PEG)–EPOB conjugates were synthesized with carbodiimide chemistry with linear PEG Methoxy‐PEG‐Carboxymethy(mPEG‐COOH) with different molecular weights (5 and 20 kDa). The products were confirmed by matrix‐assisted laser desorption/ionization time‐of‐flight mass spectroscopy and ¹H‐NMR, which showed that PEGylation only took place at the 7‐OH site of EPOB. The solubilities of PEG5K–EPOB the conjugate of mPEG‐COOH (MW 5,000) and epothilone B and PEG20K–EPOB the conjugate of mPEG‐COOH (MW 20,000) and epothilone B were determined to be 4.93 × 10^?2 and 1.58 × 10^?2 mmol/mL; this showed improvements of 35 and 11 times, respectively, over that of free EPOB (1.4 × 10^?3 mmol/mL). Moreover, the conjugates were more stable than that of free EPOB in plasma. The cytotoxicity of conjugates was evaluated on human breast cancer MCF‐7 cells with an 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐ phenytetrazoliumromide(MTT) based assay. The half maximal inhibitory concentration of a substance(IC50) values of EPOB, PEG5K–EPOB, and PEG20K–EPOB were 6.0 × 10^?4, 0.57, and 8.4 × 10^?3 μM, respectively. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 41123.     

Controlled delivery of growth‐hormone‐releasing peptide 6 from the poly(lactic‐co‐glycolic acid)–poly(ethylene glycol)–poly(lactic‐co‐glycolic acid) copolymer and the effect of a growth‐hormone‐releasing peptide 6–copolymer hydrogel on the growth of rex rabbits

Growth‐hormone‐releasing peptide 6 (GHRP‐6) plays an important role in animal growth. However, there have been few studies focusing on the effect of GHRP‐6 on animal growth through controlled release systems. We synthesized the poly(lactic‐co‐glycolic acid) (PLGA)–poly(ethylene glycol) (PEG)–PLGA copolymer to investigate its controlled released effect on GHRP‐6 in vitro and to study the effect of a GHRP‐6–copolymer hydrogel on the growth of rex rabbits. The copolymer was synthesized with ring‐opening copolymerization and characterized by ¹H‐NMR. The interaction between GHRP‐6 and the copolymer was characterized by Fourier transform infrared spectroscopy and X‐ray diffraction. The body weight, serum level of insulin‐like growth factor 1 (IGF‐1), and hair coat quality were studied in rex rabbits. The results show that hydrogen bonds formed between the N? H group in GHRP‐6 and the C?O group in the copolymer. The release mechanism of GHRP‐6 was a combination of a diffusion‐controlled mechanism and an erosion‐controlled mechanism in the copolymer. The serum level of IGF‐1, hair coat quality, and body weight were all significantly higher in the GHRP‐6–copolymer hydrogel group than in the other groups. These results indicate that the copolymer effectively controlled the release of GHRP‐6. In addition, the GHRP‐6–copolymer hydrogel increased the synthesis of IGF‐1 for a prolonged period and, thereby, increased the rex rabbits' growth and hair coat quality. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40185.