Formation of mesoglobules in aqueous media from thermo-sensitive poly(ethoxytriethyleneglycol acrylate)

A series of six poly(ethoxytriethyleneglycol acrylate) (PETEGA) homopolymers were synthesized by atom transfer radical polymerization, reversible addition-fragmentation transfer polymerization, and anionic polymerization in order to cover a molecular weight range from 7,000 to 40,000 Da. The polymers exhibited a lower critical solution temperature (LCST) behavior in water, which was observed by the occurrence of a cloud point (CP) at around 35 °C. The transmittance of visible light versus temperature dependence overlapped during the cooling and the heating cycles, showing almost a complete lack of hysteresis. Moreover, instead of the occurrence of an uncontrolled macroscopic phase separation, stable colloidal aggregates (mesoglobules) of narrow distribution in particle size were formed in water at temperatures above the LCST of PETEGA at 1 g L⁻¹ solutions. The dimensions of the mesoglobules ranged from 91 to 235 nm, and particle size was not influenced by the molecular weight of PETEGA. Temperature changes caused considerable variations of the mesoglobules dimensions, which were smaller at higher temperatures. The addition of an anionic surfactant simultaneously increased the CP values by 4–6 °C and lowered the dimensions of the mesoglobules.     

Multifunctional and thermoresponsive unimolecular micelles for tumor-targeted delivery and site-specifically release of anticancer drugs

Considering the fact that tumors have a lower pH value and a higher temperature than a normal tissue, a new type of thermoresponsive and biodegradable micelles, based on the H40-poly(?-caprolactone)-b-poly(N-isopropylacrylamide-co-acrylamide)-fluorescein methyl ester/b′-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate (i.e., H40-PCL-b-P(NIPAAm-co-AAm)-FL/b′-MPEG/PEG-FA (HPPNAP-FA)) with imaging and targeting moieties on the periphery were developed for the tumor-targeted delivery and temperature-induced site-specifically release of hydrophobic anticancer drugs. The amphiphilic HPPNAP-FA copolymer was able to self-assemble into unimolecular micelles in aqueous solution with an average diameter of 65 nm. The lower critical solution temperature (LCST) of micelles was around 39.5 °C. The anticancer drug, paclitaxel (PTX), was encapsulated into the multifunctional micelles. In vitro release studies demonstrated that the drug-loaded delivery system is relatively stable at physiologic conditions but susceptible to mild acidic environments and temperatures above LCST which would trigger the release of encapsulated drugs. Both flow cytometry and fluorescent microscopy showed that the cellular uptake of the PTX-loaded HPPNAP-FA micelles is higher than that of the PTX-loaded HPPNAP because of the folate receptor mediated endocytosis. The efficacy of this thermoresponsive drug delivery system was also evaluated at temperatures above the LCST (40 °C); the results demonstrated that the cellular uptake and the cytotoxicity of PTX-loaded micelles increase prominently. These results indicate that these multifunctional and thermoresponsive unimolecular micelles are promising biomaterials to improve the delivery efficiency and cancer specificity of hydrophobic chemotherapeutic drugs.     

Thermo- and pH-responsive HPC-g-AA/AA hydrogels for controlled drug delivery applications

This paper describes smart hydrogels composed of pH-sensitive poly(acrylic acid) (PAA) and biodegradable temperature-sensitive hydroxypropylcellulose-g-acrylic acid (HPC-g-AA) for controlled drug delivery applications. In a pH-responsive manner, the hydrogels with the higher HPC-g-AA content resulted in the lower equilibrium swelling. Although temperature had little influence on the swelling of the hydrogels, optical transmittance of the hydrogels was changed as a function of temperature, which reflecting that the HPC parts of hydrogel became hydrophobic at temperature above the lower critical solution temperature (LCST). Scanning electron microscopic analysis revealed that the pore size and the morphology of the hydrogels could be controlled by changing the composition of AA and the crosslinking density. Using BSA as a model drug, in vitro drug release experiment was carried out in artificial gastric juice (pH = 1.2) for the first 2 h and then in artificial intestinal liquid (pH = 6.8) for the subsequent 6 h. The release profiles indicated that both HPC-g-AA and AA contents played important roles in the drug release behaviors. The temperature- and pH-responsive HPC-g-AA/AA hydrogels might be exploited for wide applications in controlled drug delivery.     

Revisiting the time for removing the unloaded drug by dialysis method based on a biocompatible and biodegradable polymer vesicle

Polymer vesicles have been widely explored as drug delivery carriers. However, there are still several notable problems in the determination of the drug loading content (DLC) and the drug loading efficiency (DLE) of the drug delivery vehicles. Presented in this paper is the reconsideration of various important factors in the measurement of the DLC and DLE based on an ‘instant’ biocompatible and biodegradable polymer vesicle which can be directly dissolved in water, with a focus on the study on the time for removing the free drug. Firstly, an anti-cancer drug, doxorubicin (DOX), was successfully encapsulated into a highly biocompatible and biodegradable poly(ε-caprolactone)-block-poly[2-(methacryloyloxy)ethyl phosphorylcholine] (PCL-b-PMPC) diblock copolymer vesicle. Secondly, a specific methodology for removing the unencapsulated drug by dialysis method before the drug release experiment has been established to verify the DLC and the DLE of DOX. A number of important factors have been investigated, such as the period of time for removing the free drug, the temperature and the volume of water outside the dialysis tube, etc. Finally, the DOX release experiment was carried out at pH 5.0 and pH 7.4 with the cumulative release percentages of 55% and 35% after 24 h when the DOX feeding was 1.0 mg. As PCL-b-PMPC vesicles absorb UV light, the DOX encapsulated in polymer vesicles was calculated by subtracting the UV absorbance of vesicle solution from the UV absorbance of DOX-loaded vesicle solution at different DOX feedings of 1.0, 3.0 and 5.0 mg. We also found the appropriate calibration curves at different solution conditions were of great significance for the calculation of DLC and DLE.     

Effect of poly(ethylene glycol)-derived crosslinkers on the properties of thermosensitive hydrogels

Three crosslinkers, poly(ethylene glycol) diacrylate (PEGDA), glycerol ethoxylate triacrylate (GETA) and citric acid-(PEG acrylate)₃ (CA-PEGTA) derived from poly(ethylene glycol) (PEG) were synthesized at first. The three series of poly (N-isopropylacrylamide) (PNIPAAm) hydrogels were prepared by photopolymerization with the crosslinkers and compared with a hydrogel based on commercial crosslinker, N,N′-methylene bis-acrylamide (NMBA). The influence of the crosslinker structures and contents on the swelling behaviour, mechanical properties, and drug release of the hydrogels was investigated. The results showed that the hydrogels based on PEGDA and NMBA exhibited the highest and the lowest swelling ratio, respectively. The content of crosslinker of all hydrogel series showed good thermosensitivity and thermo-reversibility. The critical gel transition temperature (CGTT) appeared at 32 °C for the hydrogel based on NMBA, but appeared at about 34 °C for other hydrogels due to higher hydrophilicity of the crosslinker. In the mechanical properties, three-arms crosslinker GETA and CA-PEGTA led to higher mechanical strength than a linear crosslinker PEGDA. A hydrogel based on GETA (NG6) showed the highest shear modulus of 656.9 kPa and Young’s modulus of 1655.0 kPa. The hydrogels containing higher content of crosslinker revealed lower swelling ratio and higher mechanical strength. In the drug release, the hydrogels with higher swelling ratios showed higher drug absorbed. The highest release percentage of caffeine and vitamin B12 for hydrogel based on PEGDA (NP6) could reach 68.3% and 75.4%, respectively. In addition, the bound water and toxicity of the hydrogels were also investigated.

     

Dual-sensitive and folate-conjugated mixed polymeric micelles for controlled and targeted drug delivery

For this study, we prepared a new type of drug carrier with the characteristics of stimuli-responsive transition and tumor-specific recognition through the co-assembly of two series of amphiphilic block copolymers, poly(ε-caprolactone)-b-poly[triethylene glycol methacrylate-co-N-methacryloyl caproic acid] and poly(ε-caprolactone)-b-poly[triethylene glycol methacrylate-co-N-(2-(methacrylamido)ethyl) folatic amide]. The pH-dependent thermal transition and the content of the targeting ligands of the mixed polymeric micelles are well correlated with the chemical structures and compositions of these two copolymers. Doxorubicin-loaded mixed polymeric micelles are stable at body temperature in the neutral condition for prolonged circulation in blood vessels, and demonstrated rapid drug release at acidic pH levels. The cumulative drug release profiles showed a relatively slow release at pH 7.4, and a quick release of 85% in 3 h at pH 5.3. The cytotoxicity tests against FA-positive (HeLa) and FA-negative (HT-29) tumor cell lines suggest that this mixed polymeric micelle system has potential merits as a controlled and targeted drug delivery system.     

Bioinspired photo-degradable amphiphilic hyperbranched poly(amino ester)s: Facile synthesis and intracellular drug delivery

A novel amphiphilic photo-degradable hyperbranched polymer was reported at the first time. The hyperbranched o-nitrobenzyl containing poly(amino ester)s (HPAE) were prepared by one-pot Michael addition polymerization. The photo-induced degradation of hyperbranched poly(amino ester)s was confirmed by gel permeation chromatography (GPC) and UV-vis spectra. Bioinspired phosphorylcholine grafted HPAE (HPAE-PC) was synthesized via thiol-ene click chemistry. HPAE-PC can self-assemble to micelles and the micelles could be disassembled under UV irradiation because of the photo-degradation of HPAE. HPAE-PC micelles were used to load anticancer drug Doxorubicin (DOX). In vitro drug release studies showed that the release of DOX was much faster in the presence of UV irradiation than that without UV irradiation. The fluorescence microscope results indicated that DOX-loaded micelles exhibited faster drug release in A549 cells after UV irradiation. Moreover, the DOX-loaded HPAE-PC micelles under UV irradiation exhibited better anticancer activity against A549 cells than that of the nonirradiated ones. The novel amphiphilic photo-degradable hyperbranched polymers can be used to construct spatiotemporal on-demand drug delivery system for cancer therapy.     

Synthesis and characterisation of stimuli-responsive poly(N,N′-diethylacrylamide) hydrogels

Stimuli-responsive poly(N,N′-diethylacrylamide) gels were prepared by free radical polymerisation in aqueous solution, using N,N-methylenebisacrylamide as crosslinking agent. The gels were compared with the corresponding poly(N-isopropylacrylamide)-based gels. In particular, the swelling ratio of both gel types including the effect of the crosslinker content, their swelling and deswelling kinetics, their permeability and finally their drug (insulin) storage and controlled release ability were compared. In spite of the similarity in the monomer/crosslinker ratio, the deswelling kinetics and the critical temperatures (ca. 30-32 °C in pure water), some differences could be observed. Compared to poly(N-isopropylacrylamide)-based gels, poly(N,N′-diethylacrylamide)-based gels show a broader phase transition temperature interval, a more pronounced dependency of the swelling ratio on the crosslinker content, slower reswelling kinetics, a higher ingress percentage for dextran standards ranging from 5 to 70 kD, but lower ingress percentages for proteins (BSA, insulin) and much faster drug (insulin) release kinetics. While a non-linear release kinetic was observed in the case of the poly(N-isopropylacraylamide)-based gels both in water and in PBS (phosphate buffered saline), this was not the case for the poly(N,N′-diethylacrylamide)-based gels.     

Super porous α-, β-, γ-cyclodextrin cryogels with high active agent loading and controllable release profiles

Cyclodextrins (CDs) are truncated cone-like structures that are natural cyclic oligosaccharides. Here, a simple preparation method for super porous poly(α-CD), poly(β-CD), and poly(γ-CD) cryogels crosslinking with divinyl sulfone at 150%, 100% and 125% mole ratios with respect to the α-CD, β-CD, and γ-CD molecules, respectively, under cryogenic conditions, is reported. The interconnected homogeneous pore distribution of CD-based cryogels with pore sizes in the range of 5–100 μm is confirmed by SEM analysis. The CD-based cryogels weighing 10 mg are determined as hemocompatible with <1% hemolysis ratios and >79% blood clotting indexes; whereas the same materials weighing 1 mg are biocompatible with >75% cell viability on L929 fibroblasts. Additionally, active agent adsorption/delivery efficiencies of CD-based cryogels utilizing two active agents, Bisphenol A (BPA, a carcinogenic compound) and Curcumin (CUR, a polyphenolic compound), are individually evaluated. It was revealed that p(γ-CD) cryogels exhibited the highest active agent loading capacity for BPA, 87 ± 13 mg/g, whereas p(α-CD) cryogels showed the highest loading capacity for CUR, 136 ± 4 mg/g. Moreover, the active agent release from p(α-CD), p(β-CD), and p(γ-CD) cryogel networks at pH 7.4 and 37°C were determined as 40.6 ± 2, 35.3 ± 2, and 34 ± 1 mg/g for BPA, and 1.07 ± 0.2, 1.27 ± 0.1, and 1.37 ± 0.1 mg/g for CUR, respectively, within 96 h.     

Super-macroporous composite cryogels based on biodegradable dextran and temperature-responsive poly(N-isopropylacrylamide)

This contribution describes the fabrication of super-macroporous cryogels comprising an interpenetrating network of biodegradable dextran and temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) segments. Cryogels were prepared from nonmodified dextran and N-isopropylacrylamide (NIPAAm) via cryogenic treatment of their aqueous solutions and subsequent irradiation with Ultraviolet light. The weight ratio of the two precursors was varied in order to find out the proper conditions for producing cryogels of high gel fraction yield and favorable physico-mechanical properties. Temperature-responsive behavior and enhanced elastic modulus were established for cryogel materials containing ≥50 wt% PNIPAAm. Scanning electron microscopy study revealed an open-porous structure of cryogels below and above the temperature of volume phase transition. Such morphology featured a very quick response of the material to temperature changes. The capability of dextran/PNIPAAm cryogels for instant release of water-soluble substances was demonstrated as well.     

Development of a novel smart carrier for drug delivery: Ciprofloxacin loaded vaterite/reduced graphene oxide/PCL composite coating on TiO2 nanotube coated titanium

In the field of orthopaedic implants, post-surgery infections and biocompatibility are the most challenging obstacles. Sustained and controlled antibiotic release is a key factor in novel drug delivery systems. A novel drug delivery system combined with vaterite microsphere, graphite oxide (GO), reduced graphene oxide (rGO) incorporated in a polycaprolactone (PCL) matrix on TiO₂ nanotube coated Ti (TNT-Ti) is established. Anodization was employed to develop TiO₂ nanotubular arrays on Ti. Ciprofloxacin hydrochloride (CPF–HCl) loaded vaterite microspheres were synthesized by in situ precipitation method. Deposition of vaterite/PCL, vaterite-GO/PCL and vaterite-rGO/PCL composite coating on TNT-Ti was carried out by dip coating method. The composite coatings were characterized for their phase content, morphological features and functional groups. Among the three types of composite coatings, vaterite-rGO/PCL composite coating is found to be capable of encapsulating CPF-HCl to a level of 75.14 μg. The drug release profile of CPF-HCl from the vaterite-rGO/PCL composite coating exhibits a controlled release amounting to only 35.02 % of release at the end of 120 h. The vaterite-rGO/PCL composite coating exhibits a low dissolution rate and possesses adequate bioactivity in HBSS and SBF solutions at 37 °C for 14 and 10 days, respectively. The in situ loaded CPF-HCL drug on vaterite microspheres, PCL polymer matrix and GO/rGO nanofillers does not affect the cytocompatibility and all the composite coatings supported cell viability and proliferation. The ability of vaterite-rGO/PCL composite coating to provide a slow and steady release of antibiotics with sufficient bioactivity and biocompatibility at the tissue implant interface makes it a promising for osteomyelitis infection of bone tissue implant materials.     

Control of mesoporous properties of carbon cryogels prepared from wattle tannin and furfural

Wattle tannin–furfural (TFu) carbon cryogels are synthesized by sol–gel polycondensation of wattle tannin with furfural by using sodium hydroxide (NaOH) as a catalyst, dried by freeze-drying technique and then pyrolyzed under inert atmosphere, respectively. The amounts of wattle tannin (T), furfural (Fu), NaOH (C) and distilled water (W) are changed for preparing the mesoporous TFu carbon cryogels. The mole ratio of tannin to catalyst T/C plays a crucial role for the synthesis of TFu organic and carbon cryogels. The results suggest that the T/C ratio should be above 0.25 but <1.0 to prepare the mesoporous and homogeneous cryogels. Although TFu carbon cryogels have the broad mesopore size distribution, the mesoporous structure is controllable by the synthesis conditions. The carbon cryogels possess the mesopore volume less than 0.56 cm³/g and the BET surface area less than 600 m²/g. Moreover, the ratio of catalyst to water C/W can be used to prepare the homogeneous and mesoporous carbon cryogels, and to control the mesopore radius of carbon cryogels in the range of 1.6–9.6 nm.     

Polypropylene grafted with NIPAAm and APMA for creating hemocompatible surfaces that load/elute nalidixic acid

Polypropylene (PP) films grafted with N-isopropylacrylamide (NIPAAm) and N-(3-aminopropyl) methacrylamide hydrochloride (APMA) were tested as components of medical devices able to load and to sustain the release of the antimicrobial agent nalidixic acid. A pre-irradiation method was applied for grafting PP films with two NIPAAm:APMA weight ratios and to various extents. The grafting composition was analyzed recording FTIR–ATR spectra. PP-g-(1NIPAAm-r-0.5APMA) exhibited the temperature-responsiveness of PNIPAAm, while the grafting with a greater content in APMA led to that PP-g-(1NIPAAm-r-1APMA) remained highly swollen at 37 °C. The greater the content in APMA on the PP surface, the higher the amount of nalidixic acid loaded (up to 0.036 mg/cm²) and the slower the release rate in phosphate buffer pH 7.4. Coating with carboxymethyl-dextran (CM-dextran) of some drug-loaded films led to minor drug unloading while remarkably high amounts of dextran were deposited (up to 0.50 mg/cm²). This coating did not significantly modify the drug release rate neither the hemocompatibility of the PP-g-(NIPAAm-r-APMA) films, which was per se very good. Drug-loaded films remarkably inhibited the growth of Escherichia coli in in vitro microbiological tests.     

Drug release kinetics from monolayer films of glucose-sensitive microgel

To study the drug release behaviors of glucose-sensitive poly(N-isopropylacrylamide-co-3-acrylamidophenylboronic acid) (P(NIPAM-PBA)) microgels, P(NIPAM-PBA) microgel monolayers were prepared by the modification of poly(N-isopropylacrylamide-co-acrylic acid) microgel monolayers with 3-aminophenylboronic acid under EDC catalysis. Alizarin Red S (ARS) and FITC-labeled insulin (FITC-insulin) were loaded in the monolayers respectively. Their release kinetics under various conditions were measured. For both drugs, at low temperature, the drug release can be described as passive diffusion of the drugs. At temperature higher than the phase transition temperature, however, the drugs are released via a “squeeze-out” mechanism. Glucose-regulated release for both drugs was observed. At all temperatures glucose enhances the release of ARS because it competes with ARS for binding with PBA groups. For FITC-insulin, glucose enhances its release at 4 °C, but retards at 37 °C. These results will guide the design of self-regulated insulin release systems based on P(NIPAM-PBA) microgels.     

Poly(Caprolactone)‐Poly(N‐Isopropyl Acrylamide)‐Fe3O4 Magnetic Nanofibrous Structure with Stimuli Responsive Drug Release

Poly(caprolactone; PCL)—poly(N‐isopropylacrylamie; PNIPAAm)—Fe₃O₄ fiber, that can be magnetically actuated, is reported. Here, a structure is engineered that can be utilized as a smart carrier for the release of chemotherapeutic drug via magneto‐thermal activation, with the aid of magnetic nanoparticles (MNPs). The magnetic measurement of the fibers revealed saturation magnetization values within the range of 1.2–2.2 emu g^?1. The magnetic PCL‐PNIPAAm‐Fe₃O₄ scaffold shows a specific loss power value of 4.19 W g^?1 at 20 wt% MNPs. A temperature increase of 40 °C led to a 600% swelling after only 3 h. Doxorubicin (DOX) as a model drug, demonstrates a controllable drug release profile. 39% ± 0.92 of the total drug loaded is released after 96 h at 37 °C, while 25% drug release in 3 h at 40 °C is detected. Cytotoxicity results show no significant difference in cell attachment efficiency between the MNP‐loaded fibers and control while the DOX‐loaded fibers effectively inhibited cell proliferation at 24 h matching the drug release profile. The noncytotoxic effect, coupled with the magneto‐thermal property and controlled drug release, renders excellent potential for these fibers to be used as a smart drug‐release agent for localized cancer therapy.     

Synthesis and physicochemical characterization of amphiphilic block copolymers bearing acid-sensitive orthoester linkage as the drug carrier

Amphiphilic block copolymers bearing an acid-sensitive orthoester linkage, composed of hydrophilic poly(ethylene glycol) (PEG) and hydrophobic poly(γ-benzyl L-glutamate) (PBLG), were prepared as the carrier capable of selectively releasing the hydrophobic drug at the mildly acidic condition. Diblock copolymers with various lengths of PBLG were synthesized via ring opening polymerization of benzyl glutamate NCA in the presence of the acid-labile PEG as a macroinitiator. Owing to their amphiphilicities, the copolymers formed spherical micelles in aqueous conditions, and their particle sizes (22-106 nm in diameter) were dependent on the block length of PBLG. These nanoparticles were stable in the physiological buffer (pH 7.4), whereas they were readily decomposed under the acidic condition. In particular, the block copolymer with a smaller hydrophobic portion was rapidly disassembled under the acidic condition. Doxorubicin (DOX), chosen as the model anti-cancer drug, was effectively encapsulated into the hydrophobic core of the micelles using the solvent casting method. The loading efficiency depended on the hydrophobic block length of the copolymer; i.e., the longer hydrophobic block allowed for loading of larger amounts of the drug. In vitro release studies demonstrated that DOX was slowly released from the pH-sensitive micelles in the physiological buffer (pH 7.4), whereas the release rate of DOX significantly increased under the acidic condition (pH 5.0). From the in vitro cytotoxicity test, it was found that DOX-loaded pH-sensitive micelles showed higher toxicity to SCC7 cancer cells than DOX-loaded micelles without the orthoester linker. These results suggest that the amphiphilic block copolymer bearing the orthoester linkage is useful for pH-triggered delivery of the hydrophobic drug.     

Improvement of mesoporosity of carbon cryogels by acid treatment of hydrogels

Wattle tannin–furfural (TFu) gels are synthesized by the sol–gel polycondensation of wattle tannin with furfural by using sodium hydroxide as a catalyst and cured at 363 K. After cured, the TFu hydrogels are treated in hydrochloric acid (HCl) solutions with various variables as follows: aging temperature, HCl concentration and pH. TFu cryogels aged are then freeze-dried and pyrolyzed under an inert atmosphere to obtain TFu carbon cryogels. The TFu and carbon cryogels were characterized by N₂ adsorption and scanning electron microscope. The high HCl concentration yields the increase of mesopore volume almost twice especially at high temperature and the mesopore size distribution can be greatly developed sharper and narrower when the high concentration of HCl or/and the high temperature are used. Moreover, this method is the versatile approach for developing the mesopore structure of the low and high porous TFu hydrogels and has no serious problem of weight loss after treatment.     

Preparation of reduction-triggered degradable microcapsules for intracellular delivery of anti-cancer drug and gene

The reduction-triggered degradable poly(methacrylic acid-co-N,N-bis(acryloyl)cystamine)/polyethyleneimine (P(MAA-co-BAC)/PEI) microcapsules were prepared by distillation–precipitation polymerization for delivery of anti-cancer drug and gene. N,N-bis(acryloyl)cystamine (BAC) as a crosslinker containing a disulfide bond can be triggered by reductive agents, such as glutathione (GSH) and dithiothreitol (DTT), to endow the functional microcapsules with reduction-triggered drug release. The P(MAA-co-BAC)/PEI microcapsules were characterized by transmission electron microscopy (TEM), Fourier-transform infrared spectra (FT-IR), laser particle size analyzer and elemental analysis. The degradable behavior of microcapsules was investigated by analysis of UV-vis spectroscopy. The controlled drug release behavior for P(MAA-co-BAC)/PEI microcapsules was strongly dependent on the absence/presence of GSH and the pH values with doxorubicin hydrochloride (DOX) as a model drug molecule. The in vitro gene transfection ability was evaluated by Hela cells with the transfection of plasmid DNA (pDNA) encoded with green fluorescent protein (GFP) and the transfection efficiency was determined by confocal fluorescence microscopy. Furthermore, the cytotoxicities of (P(MAA-co-BAC)/PEI) microcapsules before and after loading of DOX were assessed via WST-1 assay. The P(MAA-co-BAC)/PEI microcapsules provide the potential novel vectors for delivery of drugs and genes, promising for future applications in anticancer drug and gene combined therapy.     

Immunoglobulin G recognition with Fab fragments imprinted monolithic cryogels: Evaluation of the effects of metal-ion assisted-coordination of template molecule

In this study, we applied the epitope imprinting approach to prepare molecularly imprinted monolithic cryogels for immunoglobulin G (IgG) recognition. In this respect, we imprinted F_ab fragments of IgG molecules instead of intact protein molecules via two different non-covalent interactions. In the first approach, we directly coordinated F_ab fragments with N-methacryloyl-L-histidine (MAH), polymerizable derivative of L-histidine, but for the second, we used cupric ions [Cu(II)] as mediator between MAH and F_ab fragments. The monolithic cryogels were characterized by Fourier transform infrared (FTIR) spectroscopy, swelling test, and scanning electron microscopy. Then, the monolithic cryogels were used for F_ab fragment adsorption from aqueous solution while evaluating the factors such as pH and F_ab fragment concentration affecting on adsorption process in continuous set-up. After that, monolithic cryogels were used for IgG adsorption by varying pH, IgG concentration, flowrate, and temperature in appropriate ranges. Maximum IgG adsorption capacities were determined as 32.4 mg/g and 49.0 mg/g for directly coordinated cryogel (MIP_Direct) and Cu(II) assisted cryogel (MIP_{Cu(II) assisted}), respectively. Non-imprinted monolithic cryogels were also prepared for control purposes. In addition to F_ab fragments and IgG molecules, albumin and F_c fragment of IgG molecules were used as competitor biomolecules in order to investigate the selectivity gained by imprinting process. Relative selectivity constants were calculated as 1.47, 2.64 and 3.89 for MIP_Direct and 2.90, 8.98, and 11.51 for MIP_{Cu(II) assisted} for F_ab/IgG, F_ab/F_c, and F_ab/albumin as biomolecule pairs, respectively. The desorption efficiency and reusability of MIP_{Cu(II) assisted} cryogel were better than that of MIP_Direct. The results reported here showed that the metal ion assistance improved the selectivity features of the imprinted cryogels and allowed to study under milder conditions with enhanced adsorptive properties.     

Mechanically Robust Shape-Memory Organohydrogels Based on Silk Fibroin with Organogel Microinclusions of Various Sizes

Organohydrogels (OHGs) are soft materials with antagonistic hydrophilic and hydrophobic domains that have great interest for many different applications. This study presents the preparation of mechanically strong OHGs with shape-memory function by incorporating semicrystalline organo-microgels within the pores of silk fibroin (SF) scaffolds. In the first step, SF cryogels with various pore diameters between 26 ± 8 and 17 ± 4 µm are synthesized by cryogelation of aqueous SF solutions at concentrations between 5 and 20 w/v%. In the second step, the pores of SF scaffolds are filled with an organogel precursor solution containing n-octadecyl acrylate (C18A), acrylic acid, N,N'-methylene(bis)acrylamide, and an initiator. Once the free-radical polymerization took place inside the pores, OHGs containing organo-microgels of various sizes are obtained. The incorporation of the organogel component in the cryogels generates crystalline areas due to the side-by-side packed C18 side chains. OHGs' melting temperature and crystallinity level can be varied from 42 to 54 °C and from 2 to 16%, respectively. The stiffness of OHGs increases from 5.9 ± 0.5 to 18 ± 1 MPa with increasing SF concentration from 5 to 20 w/v%, which is attributed to the decreasing pore size of the cryogels and increasing thickness of the pore walls.