Refined control of thermoresponsive swelling/deswelling and drug release properties of poly(N-isopropylacrylamide) hydrogels using hydrophilic polymer crosslinkers

Thermoresponsive poly(N-isopropylacrylamide) (PNIPAm)-based hydrogels are widely investigated for their ability to alter their physical properties (e.g. dimensions, swelling/deswelling) in response to change in temperature. Despite extensive research efforts, it is still challenging to control various aspects of thermoresponsive physical properties of PNIPAm hydrogels in an efficient and comprehensive manner using conventional small molecular crosslinkers due to their limited solubility and functional groups. Herein, thermoresponsive swelling/deswelling behavior of PNIPAm hydrogels is tuned in a wide range by hydrophilic polymeric crosslinkers with varying chain lengths. The concentration and molecular weight of the poly(ethylene glycol) (PEG) crosslinker are varied to control the swelling/deswelling behavior, drug release, and lower critical solution temperature (LCST) of PNIPAm-PEG hydrogels. Compared with PNIPAm hydrogels crosslinked with a conventional small molecular crosslinker, N,N′-methylenebisacrylamide, greater degree and range of thermoresponsive swelling/deswelling as well as tunable LCST are demonstrated for PNIPAm-PEG hydrogels. In addition, more swelling-controlled PNIPAm-PEG hydrogels displayed more sustained and variable thermoresponsive drug release based on their crosslinking density, by modulating the hydrophobic transition of PNIPAm chains with hydrophilic PEG chains. In sum, various thermoresponsive properties of PNIPAm hydrogels could be controlled by hydrophilic polymeric crosslinkers, and this strategy could be applied to various hydrogel systems to control their physical properties for biomedical applications.     

Building a polysaccharide hydrogel capsule delivery system for control release of ibuprofen

Development of a delivery system which can effectively carry hydrophobic drugs and have pH response is becoming necessary. Here we demonstrate that through preparation of β-cyclodextrin polymer (β-CDP), a hydrophobic drug molecule of ibuprofen (IBU) was incorporated into our prepared β-CDP inner cavities, aiming to improve the poor water solubility of IBU. A core-shell capsule structure has been designed for achieving the drug pH targeted and sustained release. This delivery system was built with polysaccharide polymer of Sodium alginate (SA), sodium carboxymethylcellulose (CMC) and hydroxyethyl cellulose (HEC) by physical cross-linking. The drug pH-response control release is this hydrogel system’s chief merit, which has potential value for synthesizing enteric capsule. Besides, due to our simple preparing strategy, optimal conditions can be readily determined and the synthesis process can be accurately controlled, leading to consistent and reproducible hydrogel capsules. In addition, phase-solubility method was used to investigate the solubilization effect of IBU by β-CDP. SEM was used to prove the forming of core and shell structure. FT-IR and ¹H-NMR were also used to perform structural characteristics. By the technique of UV determination, the pH targeted and sustained release study were also performed. The results have proved that our prepared polysaccharide hydrogel capsule delivery system has potential applications as oral drugs delivery in the field of biomedical materials.     

PEG-g-chitosan thermosensitive hydrogel for implant drug delivery: cytotoxicity,in vivo degradation and drug release

Thermosensitive hydrogels based on chitosan are of great interests for injectable implant drug delivery. The poly(ethylene glycol)-grafted-chitosan (PEG-g-CS) hydrogel was reported as a potential thermosensitive system. The objective of the present study is to evaluate the cytotoxicity, in vivo degradation and drug release of PEG-g-CS hydrogel. Cytotoxicity was evaluated using L929 murine fibrosarcoma cell line. Degradation and drug release in vivo were investigated by subcutaneous injection of the hydrogel into Sprague-Dawley rats. PEG-g-CS polymer exhibits no significant cytotoxicity when its concentration is less than 3 mg mL^?1. After being implanted, PEG-g-CS hydrogel maintains its integrity for two weeks and collapses, merging into the tissue, in the third week. It causes moderate inflammatory response but no fibrous encapsulation around the hydrogel is found. The hydrogel presents a three-week sustained release of cyclosporine A with no significant burst release in vitro and produces the effective drug concentration in blood for more than five weeks in vivo, performing almost the same bioavailability to chitosan/glycerophosphate hydrogel. Further modifications of PEG-g-CS hydrogel might be necessary to modulate the degradation and to mitigate the fluctuations in blood drug concentration.     

Development and evaluation of a novel polymeric hydrogel of sucrose acrylate-co-polymethylacrylic acid for oral curcumin delivery

A monomer of sucrose acrylate (AC-sucrose) was synthesized by conjugating starting compound sucrose with methyl acrylate (MA). The obtained AC-sucrose was characterized by mass spectrometry (MS) and Fourier transform infrared (FTIR) spectroscopy. AC-sucrose was selected as a monomer to fabricate a novel pH sensitive hydrogel via free radical polymerization. The inner morphology of the final hydrogel was observed with an S-4800 scanning electron microscope (SEM). The swelling and de-swelling behaviors of the hydrogel chips were also studied. Curcumin (CUR) was selected as a model drug and loaded into the final hydrogel. The release profiles of CUR were performed via dialysis method in pH 1.2, 6.8 and 7.4 buffers, respectively. Mass and FTIR spectra confirmed the synthesis of AC-sucrose. SEM photographs showed that poly(AC-sucrose-co-MAA) hydrogels had many 3D meshes. In pH 1.2 buffer, the hydrogel chips showed the biggest swelling ratio (SR) of 34.4 ± 1.9%. However, in pH 7.4 buffer, the SRs of the hydrogel chips reached to 368.7 ± 28.0%, which suggested that the hydrogel had an excellent pH sensibility. The releasing profiles showed that only 4.6 ± 0.4% of CUR was released in pH 1.2 buffer but 93.7 ± 4.7% of CUR was diffused into pH 7.4 buffer. These data suggested that the CUR-loaded poly (AC-sucrose-co-MAA) hydrogel could direct CUR to release in basic environments.     

Macroporous poly(sucrose acrylate) hydrogel for controlled release of macromolecules

We have studied the controlled release of proteins from poly(sucrose acrylate) hydrogels. The hydrogels were prepared by a two-step procedure in which sucrose was first acylated to sucrose-1′-acrylate followed by free radical polymerization. By adjusting the cross-link ratio and initial monomer concentration, the swelling ratio of the hydrogel was varied from five to 28. The mechanical strength of these hydrogels was comparable to that of other hydrogels with approximately the same swelling ratio. Scanning electron micrographs and mesh size calculations indicate that the hydrogel is macroporous, suggesting it may be suitable for a variety of biomedical applications. The release kinetics of β-lactoglobulin, bovine serum albumin and γ-globulin were studied as a function of initial monomer concentrations for the sucrose-based hydrogel. All of the release profiles were characterized by an initial burst of protein in the first 25 h followed by a long period of sustained release (s> 500 h). The magnitude of the initial burst was reduced by increasing the initial monomer concentration and by increasing the molecular weight of the protein. A quantitative model based on the heterogeneous nature of the hydrogel was developed to explain the observed release kinetics.     

Self-assembled nanoparticles made from a new PEGylated poly(aspartic acid) graft copolymer for intravaginal delivery of poorly water-soluble drugs

New amphiphilic PEGylated poly(aspartic acid) graft copolymer (PASP-PEG-Ph) was synthesized as a nanocarrier for intravaginal drug delivery of poorly water-soluble drugs. PASP-PEG-Ph self-assembled into negatively charged spherically shaped nanoparticles in the presence of pH 4.5 and pH 7.0 vaginal fluid simulants with a diameter of approximately 200 nm as evidenced by Zeta-potentiometer, scanning electron microscope (SEM), dynamic light scattering (DLS) analysis. A significant number of stable NPs could be maintained at pH 4.5, 37 °C for 13 days. The PASP-PEG-Ph NP showed no significant cytotoxicity toward the T-cell line SupT1 and human vaginal epithelial cell line Vk2/E6E7 up to 1 mg/mL. The highest encapsulation efficiency of the model drug coumarin 6 (C6) by PASP-PEG-Ph was 92.0 ± 5.7%. The sustained release profile of the encapsulated C6 was demonstrated by an in vitro release study. An in vitro cellular uptake study revealed strong cellular uptake of the C6 loaded NP by SupT1 cells within 2 h.     

Synthesis of poly(glutamic acid)-tyramine hydrogel by enzyme-mediated gelation for controlled release of proteins

An in situ-formed hydrogel was synthesized by enzymatic cross-linking of poly(γ-glutamic acid)–tyramine conjugates (PGA–Tyr) using horseradish peroxidase (HRP) and hydrogen peroxide (H₂O₂). The gelation time ranged from 25 s to 5 min was accomplished by tuning the concentration of HRP, H₂O₂/Tyr molar ratio and the degree of substitution (DS) of Tyr groups. The storage modulus (G′), cross-link density, and mesh size can be tailored by controlling the H₂O₂/Tyr ratio and DS. The rheological analysis indicated that the storage modulus (G′) can be tailored from approximately 40 to over 1100 Pa with the increasing H₂O₂/Tyr ratio and DS. The bovine serum albumin (BSA) was used as model protein and encapsulated into the hydrogel during the enzyme-mediated cross-linking reaction. Controlled release of BSA in vitro from the PGA–Tyr hydrogel was obtained. The release rate and cumulative release amount of encapsulated BSA were manipulated by controlling the H₂O₂/Tyr ratio and DS. More than 90% of encapsulated BSA was released from the hydrogel with low cross-link density and lager mesh size in 60 h, while only 68% of BSA was released from the hydrogel with high cross-link density and small mesh size. The results indicated that the PGA–Tyr hydrogel is a promising material for the controlled release of therapeutic protein or peptides.     

A facile method to fabricate thermo- and pH-sensitive hydrogels with good mechanical performance based on poly(ethylene glycol) methyl ether methacrylate and acrylic acid as a potential drug carriers

Abstract

A thermo- and pH-sensitive hydrogel was prepared by a facile free aqueous radical copolymerization of PEGMA and AAc without any crosslinkers for controlled drug delivery. The successful fabrication of hydrogels was confirmed by Fourier transform infrared spectroscopy (FT-IR) and thermo gravimetric analysis (TGA) measurements. The morphological, mechanical and swelling properties of the obtained hydrogels were studied systematically. The results showed that the morphological and mechanical behaviors of the resultant hydrogels were strongly affected by the content of AAc. Moreover, the obtained hydrogels showed an excellent thermo-, pH- and salinity sensitivities. Release profiles of 5-Fu were studied at different pH (gastric pH 1.2 and intestinal pH 7.4) and temperatures (25?°C and 37?°C). The results showed that the release is very low at pH 1.2/37?°C and high at pH 7.4/25?°C. The cytotoxicity of hydrogels to cells was determined by an MTT assay. The result demonstrated that the blank hydrogels had negligible toxicity to cells, whereas the 5-Fu-loaded hydrogels remained high in cytotoxicity for LO2 and HepG-2 cells. Results of the present investigation exemplify the potential of this novel thermo- and pH-sensitive hydrogel for the controlled and targeted delivery of the anti cancer drug 5-Fu.     

Synthesis,characterization and controlled drug release from temperature-responsive poly(ether-urethane) particles based on PEG-diisocyanates and aliphatic diols

A series of linear amphiphilic poly(ether-urethane)s with alternative hydrophilic/hydrophobic segments based on PEG-diisocyanates and aliphatic diols is developed. The molecular structures of the copolymers were confirmed with nuclear magnetic resonance, Fourier transform infrared spectra and gel permeation chromatography. Nanoparticles prepared by self-assembly of the resulting copolymers show sharp temperature-responsive phase transition. The phase transition temperature could be easily modulated by the length of hydrophilic or hydrophobic segments of the polymer. The mechanism of the temperature-responsive behaviour is discussed. In the presence of these obtained poly(ether-urethane)s, doxorubicin (DOX) could be dispersed into aqueous solution. The ratio of DOX release from polymeric particles increased sharply above the phase transition temperature, while the release was suppressed below the phase transition temperature. A controlled drug release can be achieved by changing the environmental temperature. The easy-prepared polymeric nanoparticles, with features of biocompatibility, biodegradability and tail-made temperature responsiveness, are a kind of promising carriers for temperature-controllable drug release.     

A dual-application poly (dl-lactic-co-glycolic) acid (PLGA)-chitosan composite scaffold for potential use in bone tissue engineering

The development of patient-friendly alternatives to bone-graft procedures is the driving force for new frontiers in bone tissue engineering. Poly (dl-lactic-co-glycolic acid) (PLGA) and chitosan are well-studied and easy-to-process polymers from which scaffolds can be fabricated. In this study, a novel dual-application scaffold system was formulated from porous PLGA and protein-loaded PLGA/chitosan microspheres. Physicochemical and in vitro protein release attributes were established. The therapeutic relevance, cytocompatibility with primary human mesenchymal stem cells (hMSCs) and osteogenic properties were tested. There was a significant reduction in burst release from the composite PLGA/chitosan microspheres compared with PLGA alone. Scaffolds sintered from porous microspheres at 37 °C were significantly stronger than the PLGA control, with compressive strengths of 0.846 ± 0.272 MPa and 0.406 ± 0.265 MPa, respectively (p < 0.05). The formulation also sintered at 37 °C following injection through a needle, demonstrating its injectable potential. The scaffolds demonstrated cytocompatibility, with increased cell numbers observed over an 8-day study period. Von Kossa and immunostaining of the hMSC-scaffolds confirmed their osteogenic potential with the ability to sinter at 37 °C in situ.     

Cyclodextrin/poly(anhydride) nanoparticles as drug carriers for the oral delivery of atovaquone

The aim was to study the ability of bioadhesive cyclodextrin-poly(anhydride) nanoparticles as carriers for the oral delivery of atovaquone (ATO). In order to increase the loading capacity of ATO by poly(anhydride) nanoparticles, the following oligosaccharides were assayed: 2-hydroxypropyl-β-cyclodextrin (HPCD), 2,6-di-O-methyl-β-cyclodextrin (DCMD), randomly methylated-β-cyclodextrin (RMCD) and sulfobuthyl ether-β-cyclodextrin (SBECD). Nanoparticles were obtained by desolvation after the incubation between the poly(anhydride) with the ATO-cyclodextrin complexes. For the pharmacokinetic studies, ATO formulations were administered orally in rats. Overall, ATO displayed a higher affinity for methylated cyclodextrins than for the other derivatives. However, for in vivo studies, both ATO-DMCD-NP and ATO-HPCD-NP were chosen. These nanoparticle formulations showed more adequate physicochemical properties in terms of size (<260 nm), drug loading (17.8 and 16.9 μg/mg, respectively) and yield (>75%). In vivo, nanoparticle formulations induced higher and more prolonged plasmatic levels of atovaquone than control suspensions of the drug in methylcellulose. Relative bioavailability of ATO when loaded in nanoparticles ranged from 52% (for ATO-HPCD NP) to 71% (for ATO-DMCD NP), whereas for the suspension control formulation the bioavailability was only about 30%. The encapsulation of atovaquone in cyclodextrins-poly(anhydride) nanoparticles seems to be an interesting strategy to improve the oral bioavailability of this lipophilic drug.     

Glycol chitin/PAA hydrogel composite incorporated bio-functionalized PLGA microspheres intended for sustained release of anticancer drug through intratumoral injection

Abstract

A novel anti-hepatoma drug release hybrid system is prepared by using poly(acrylic acid) (PAA) and glycol chitin as substrate in combination with Paclitaxel (PTX)-loaded bio-biofunctionalized poly(lactic-co-glycolic acid) (PLGA) micro-particles, which is intended for cancer therapy through intratumoral injection. The rheological behavior of glycol chitin (7?wt%)/PAA illustrates that it has low gelling temperature (i.e. 17?°C at pH 7.56) which ensures that the formulation turns to gel at physiological condition. The gelling time of glycol chitin/PAA is 16?minutes at 25?°C and 3?minutes at 37?°C, which is convenient for doctors to inject the in-situ gel formulations into the tumor location of patient. The drug release behavior reveals that the system can dramatically postpone the drug release. The cell viability test indicates that the micro-particles with drug still have 62% inhibitory effect on hepatoma cells in the fourteenth day after combing with hydrogel. This system is a promising approach for cancer therapy through intratumoral injection of in-situ gel formulations to extend retention time at tumor sites.     

Synthetic biodegradable hydrogel delivery of demineralized bone matrix for bone augmentation in a rat model

There exists a strong clinical need for a more capable and robust method to achieve bone augmentation, and a system with fine-tuned delivery of demineralized bone matrix (DBM) has the potential to meet that need. As such, the objective of the present study was to investigate a synthetic biodegradable hydrogel for the delivery of DBM for bone augmentation in a rat model. Oligo(poly(ethylene glycol) fumarate) (OPF) constructs were designed and fabricated by varying the content of rat-derived DBM particles (either 1:3, 1:1 or 3:1 DBM:OPF weight ratio on a dry basis) and using two DBM particle size ranges (50–150 or 150–250 μm). The physical properties of the constructs and the bioactivity of the DBM were evaluated. Selected formulations (1:1 and 3:1 with 50–150 μm DBM) were evaluated in vivo compared to an empty control to investigate the effect of DBM dose and construct properties on bone augmentation. Overall, 3:1 constructs with higher DBM content achieved the greatest volume of bone augmentation, exceeding 1:1 constructs and empty implants by 3- and 5-fold, respectively. As such, we have established that a synthetic, biodegradable hydrogel can function as a carrier for DBM, and that the volume of bone augmentation achieved by the constructs correlates directly to the DBM dose.     

磁性多孔PLGA微球制备及其功能化研究

磁性微球是一种具有磁响应性的复合功能材料.以共沉淀法制备的Fe3O4纳米颗粒为铁磁性原料,通过溶剂挥发法制备Fe3O4/PLGA磁性高分子复合微球.光镜及扫描电镜观察微球形貌并测定元素组成,确定合成了粒径约为15 μm的磁性高分子复合微球;激光共聚焦观察磁性微球孔洞结构;Micro-CT及紫外可见分析碘及罗丹明B的吸附...     

PLGA/O-CMC载药纳米微粒的体外降解及释药行为研究

本研究以聚乳酸-乙醇酸共聚物（PLGA）和自行制备的O-羧甲基壳聚糖（O-CMC）为原料，以5-氟尿嘧啶（5-FU）为抗癌药物模型，采用自身设计的改良复乳法制备了载药纳米微粒。微粒平均粒径为98.5nm，粒径分布指数为0.192，粒子表面∈电位为61．48eV，载药率高达18.9％。然后用SEM动态监测载药纳米粒子降解过程中表面形貌的变化，并连续追踪粒子降解过程中的质量损失和降解介质的pH变化。载药纳米粒子在PBS中的释药行为研究表明，（1）前12h的释药动力学符合Huguchi方程，具有一级释放特性；（2）在20d内的释药动力学符合零级释放特性。细胞凋亡实验结果表明载药纳米粒子对TJ905脑胶质瘤细胞增殖有明显的抑制作用。     

Long-term in vivo performance and biocompatibility of poly(vinyl alcohol) hydrogel macrocapsules for hybrid-type artificial pancreas

A bag-shaped macrocapsule suitable for Langerhans islets entrapment and immunoisolation was constructed using a semipermeable hydrogel membrane of poly(vinyl alcohol) (PVA) cross-linked chemically and sterilized by a radiation method. Empty (not seeded with Langerhans islets), sealed, sterile macrocapsules were implanted into the intraperitoneal cavity of adult female Buffalo rats for periods of up to 6.5 months. Long-term in vivo performance of the macrocapsule membrane was evaluated on the basis of the permeability measurements of glucose and albumin. The results of experiments revealed the progressive, disadvantageous alterations of the PVA hydrogel membrane resulting in a decrease in the permeability of solutes. Histochemical examinations of the cellular enzyme activities in the implant-encapsulating tissue, regarding the acid and alkaline phosphatases, were performed to evaluate the activity of cells involved in the inflammatory response to the long-term macrocapsule implantation.     

壳聚糖-明胶/聚乳酸-羟基乙酸联合载药水凝胶的体外抗结核作用

文题释义：基质细胞衍生因子1：是一种参与免疫细胞活化、分化和迁移及伤口愈合、角膜上皮再生和组织修复等过程的趋化因子,能促进干细胞的生长和发育,参与调节成骨分化,可通过细胞归巢提高干细胞向病灶区的趋化作用。而基质细胞衍生因子1的失活会损害成骨细胞的发育和分化。此外,其还与血管生成密切相关。 异烟肼：具有较高的杀菌活性,是治疗结核病的一线药物。世卫组织建议将异烟肼作为结核病的标准疗法,用于潜伏性结核病感染者的预防治疗,与利福平、吡嗪酰胺和乙胺丁醇一起用于治疗活动性肺结核。异烟肼的活化形式与脂肪酸生物合成Ⅱ型系统中的NADH依赖型烯醇酰基载体蛋白还原酶异烟肼a结合,阻断细菌细胞壁关键成分支原体酸的合成。 背景：抗结核化疗是目前治疗骨关节结核的主要手段,然而全身给药难以维持病灶区的有效浓度,治疗效果欠佳。 目的：制备一种原位、长期释放抗结核药物且兼备促成骨作用的壳聚糖-明胶/聚乳酸-羟基乙酸联合载药水凝胶。 方法：将亲水性的抗结核药物异烟肼和疏水性的基质细胞衍生因子通过复乳法负载到聚乳酸-羟基乙酸中,制备聚乳酸-羟基乙酸载药微球,共混至壳聚糖-明胶水凝胶支架中,制备壳聚糖-明胶/聚乳酸-羟基乙酸联合载药水凝胶。检测聚乳酸-羟基乙酸载药微球、壳聚糖-明胶/聚乳酸-羟基乙酸联合载药水凝胶的体外释药与抗结核杆菌的能力。将成骨前体细胞MC3T3-E1分别接种于载药微球与联合载药水凝胶表面,CCK-8法检测细胞活力,碱性磷酸酶活性检测细胞的成骨性能。 结果与结论：①载药微球中异烟肼1 h内的突释约为23.3%,2 d内的释放率约为42.6%,随后进入缓释期,25 d后进入平台期;基质细胞衍生因子1在1 h内的累积释放率约为19.8%,2 d内的释放率约为44.7%,随后进入缓释期,25 d后进入平台期;联合载药水凝胶中异烟肼和基质细胞衍生因子1最初1 h的释放分别为8.3%和8.5%,第2天的累计释放率分别为15.2%和17.6%,远低于聚乳酸-羟基乙酸微球;②体外4周后,联合载药水凝胶的抑菌直径大于载药微球,抑菌率高于载药微球(P < 0.05);③联合载药水凝胶与载药微球均具有良好的细胞相容性,细胞活力均约为100%;④培养5,10 d后,联合载药水凝胶表面的细胞碱性磷酸酶活性与载药微球比较差异无显著性意义(P > 0.05);⑤结果表明,原位壳聚糖-明胶/聚乳酸-羟基乙酸联合载药水凝胶有作为治疗骨关节结核及其他骨关节感染的潜力。 ORCID: 0000-0003-4166-2492(张贺龙) 中国组织工程研究杂志出版内容重点：生物材料;骨生物材料; 口腔生物材料; 纳米材料; 缓释材料; 材料相容性;组织工程     

Preparation and characterization of electrospun PLGA/gelatin nanofibers as a drug delivery system by emulsion electrospinning

Novel biocompatible poly(lactide-co-glycolide) (PLGA) nanofiber mats with favorable biocompatibility and good mechanical strength were prepared, which could serve as an innovative type of tissue engineering scaffold or an ideal controllable drug delivery system. Both hydrophobic and hydrophilic drugs, Cefradine and 5-fluorouracil were successfully loaded into PLGA nanofiber mats by emulsion electrospinning. The natural bioactive protein gelatin (GE) was incorporated into the nanofiber mats to improve the surface properties of the materials for cell adhesion. Nanofibrous scaffolds were characterized by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, contact angle and tensile measurements. Emulsion electrospun fibers with GE had perfect hydrophilic and good mechanical property. The in vitro release test showed thedrugs released from emulsion electrospun fibers, which achieved lower burst release. The cells cytotoxicity experiment indicated that emulsion electrospun fibers were less toxic and tended to promote fibroblasts cells attachment and proliferation, which implied that the electrospun fibers had promising potential application in tissue engineering or drug delivery.     

Facile synthesis of magnetic-/pH-responsive hydrogel beads based on Fe3O4 nanoparticles and chitosan hydrogel as MTX carriers for controlled drug release

In the present study, methotrexate (MTX)-encapsulated magnetic-/pH-responsive hydrogel beads based on Fe₃O₄ nanoparticles and chitosan were successfully prepared through a one-step gelation process, which is a very facile, economic and environmentally friendly route. The developed hydrogel beads exhibited homogeneous porous structure and super-paramagnetic responsibility. MTX can be successfully encapsulated into magnetic chitosan hydrogel beads, and the drug encapsulation efficiency (%) and encapsulation content (%) were 93.8 and 6.28%, respectively. In addition, the drug release studies in vitro indicated that the MTX-encapsulated magnetic chitosan hydrogel beads had excellent pH-sensitivity, 90.6% MTX was released from the magnetic chitosan hydrogel beads within 48 h at pH 4.0. WST-1 assays in human liver hepatocellular carcinoma cells (HepG2) demonstrated that the MTX-encapsulated magnetic chitosan hydrogel beads had good cytocompatibility and high anti-tumor activity. Therefore, our results revealed that the MTX-encapsulated magnetic chitosan hydrogel beads would be a competitive candidate for controlled drug release in the area of targeted cancer therapy in the near future.     

Preparation and characterization of polyelectrolyte complex nanoparticles based on poly (malic acid), chitosan. A pH-dependent delivery system

The main objective of this work was to develop polyelectrolyte complex (PEC) nanoparticles based on poly (malic acid), chitosan (PMLA/CS) as pH-dependent delivery systems. The results indicated that the PMLA/CS Nps were successfully prepared. The prepared PMLA/CS Nps showed spherical morphology with a mean diameter of 212.81 nm and negative surface charge of ?24.60 mV, and revealing significant pH-sensitive properties as the mass ratio of PMLA to CS was 5:5. The prepared PMLA/CS Nps were characterized by FT-IR, TEM and DLS. The prepared PMLA/CS Nps remained stable over a temperature range of 4–53 °C. Doxorubicin (Dox) as a model drug was loaded on the nanoparticles through the physical adsorption method. The high drug loading efficiency (16.9%) and the sustained release patterns in acidic media were observed, and the release accelerated in alkaline solutions. MTT based cytotoxic analysis also depicted the non-toxic nature of PMLA/CS Nps, while Dox-PMLA/CS Nps showed dose-dependent cytotoxicity towards MDA-MB-231 cells. Hence, the nanoparticles could be potentially applied as pH sensitive drug vehicles for controlled release.