Release Of Bovine Serum Albumin Research Articles

Composite Fish Collagen-Hyaluronate Based Lyophilized Scaffolds Modified with Sodium Alginate for Potential Treatment of Chronic Wounds.

Chronic wounds are characterized by both decreased collagen deposition and increased collagen breakdown. It is reasonable to hypothesize that exogenous collagen can potentially promote wound healing by reducing degradation enzymes in the wound environment and disrupting the cycle of chronicity. Therefore, this study aimed to develop an optimal combination of fish collagen (FCOL), sodium alginate (SA), and hyaluronic acid (HA) loaded with bovine serum albumin (BSA) as a model protein fabricated as lyophilized scaffolds. The effects of sodium alginate (SA#) with higher mannuronic acid (M) were compared to sodium alginate (SA*) with higher guluronic acid (G). The SA* with higher G resulted in elegant scaffolds with hardness ranging from 3.74 N–4.29 N that were able to withstand the external force due to the glycosidic bonds in guluronic acid. Furthermore, the high G content also had a significant effect on the pore size, pore shape, and porosity. The water absorption (WA) ranged from 380–1382 (%) and equilibrium water content (EWC) 79–94 (%) after 24 h incubation at 37 °C. The SA* did not affect the water vapor transmission rate (WVTR) but incorporating BSA significantly increased the WVTR making these wound dressing scaffolds capable of absorbing about 50% exudate from a heavily exuding chronic wound. The protein released from the composite systems was best explained by the Korsmeyer–Peppas model with regression R2 values ranging from 0.896 to 0.971 and slope or n < 0.5 indicating that the BSA release mechanism was governed by quasi-Fickian diffusion. Cell viability assay showed that the scaffolds did not inhibit the proliferation of human dermal fibroblasts and human epidermal keratinocytes, and are therefore biocompatible. In vitro blood analysis using human whole blood confirmed that the BSA-loaded SA*:FCOL:HA scaffolds reduced the blood clotting index (BCI) by up to 20% compared to a commercially available sponge for chronic wounds. These features confirm that SA*:FCOL:HA scaffolds could be applied as a multifunctional wound dressing.

Conductive polypyrrole-coated electrospun chitosan nanoparticles/poly(D,L-lactide) fibrous mat: influence of drug delivery and Schwann cells proliferation

For nerve tissue engineering (NTE), scaffolds with the ability to release drugs under control and support the rapid proliferation of cells are very important for the repair of nerve defects. This study aimed to fabricate a conductive drug-loaded fiber mat by electrospinning and assess its potential as a scaffold for Schwann cells proliferation. The conductive polypyrrole (PPy) was coated on an electrospun poly (D, L-lactide) (PLA) fibrous mat, which was simultaneously embedded with protein-loaded chitosan nanoparticles and ibuprofen as a model small molecule drug. The fibrous mat shows suitable conductivity, mechanical properties, and hydrophilicity for NTE. For drug release and degradation studies, the fibrous mat can achieve sustained release of bovine serum albumin (BSA) and ibuprofen, and the PPy coating can increase the surface wettability and conductivity while slowing down the degradation of the fibrous mat. The application of electrical stimulation (ES) to the fibrous mat can accelerate the release of ibuprofen, but there was no significant effect on the release rate of the protein. The fibrous mat showed no cytotoxicity in vitro, and Schwann cells (SCs) can adhere, grow, and proliferate well on mats. At the 120th hour of culture in vitro, the relative growth rate of SCs on the conductive drug-loaded fibrous mat reached 198.22 ± 2.34%, which was an increase of 37.93% compared to the SCs on the drug-loaded fibrous mat with ES. The density and elongation of SCs on the conductive drug-loaded fibrous mat were greater than those on the PLA fibrous mat, indicating that the conductive polypyrrole-coated electrospun chitosan nanoparticles/PLA fibrous mat has good potential for application in nerve regeneration.

Light-Sensitive Phenacyl Crosslinked Dextran Hydrogels for Controlled Delivery.

Stimuli‐responsive soft materials enable controlled release of loaded drug molecules and biomolecules. Controlled release of potent chemotherapeutic or immunotherapeutic agents is crucial to reduce unwanted side effects. In an effort to develop controlled release strategies that can be triggered by using Cerenkov luminescence, we have developed polymer hydrogels that can release bovine serum albumin and immunoglobulin G by using light (254 nm–375 nm) as a trigger. We describe the synthesis and photochemical characterization of two light sensitive phenacyl bis‐azide crosslinkers that are used to prepare transparent self‐supporting hydrogel patches. One crosslinker was designed to optimize the overlap with the Cerenkov luminescence emission window, bearing an π‐extended phenacyl core, resulting in a high quantum yield (14 %) of photocleavage when irradiated with 375 nm light. We used the extended phenacyl crosslinker for the preparation of protein‐loaded dextran hydrogel patches, which showed efficient and selective dosed release of bovine serum albumin or immunoglobulin G after irradiation with 375 nm light. Cerenkov‐triggered release is as yet inconclusive due to unexpected side‐reactivity. Based on the high quantum yield, efficient release and large overlap with the Cerenkov window, we envision application of these photosensitive soft materials in radiation targeted drug release.

Smart pH-Sensitive Hydrogel Based on the Pineapple Peel-Oxidized Hydroxyethyl Cellulose and the Hericium erinaceus Residue Carboxymethyl Chitosan for Use in Drug Delivery.

Pineapple and hericium erinaceus (HE) produce a lot of residues in the process of food processing. These processed residues are good potential derivative precursors. In this investigation, a simple and non-toxic method was developed to prepare one new composite hydrogel by the Schiff base reaction between the aldehyde group of oxidized hydroxyethyl cellulose (OHEC) from processed pineapple peel residue and the amino group of carboxymethyl chitosan (CMCS) from processed HE residue. Subsequently, a series of experiments toward these new hydrogel polymers including structure characterization and performances were applied. The resultant hydrogel polymers were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy and confirmed with thermogravimetry. It was observed that the modification of cellulose and chitin was adequate, and the synthesis of OHEC/CMCS hydrogel polymers was successful. The gelation time experiments indicated that the shortest gel time was 33 s at a mass ratio of 4:6 (OHEC-70:CMCS). The hydrogel showed good swelling properties. The maximum swelling rate reached 11.58 g/g, and the swelling rate decreased with the increase of the oxidation degree of OHEC. The drug delivery applications of the prepared hydrogel were evaluated with bovine serum albumin (BSA) as a model drug releasing in vitro. It was discovered that the BSA release from the hydrogel was pH sensitive under simulated gastrointestinal conditions. All of these attributes indicate that the novel prepared hydrogel polymers have the potential as good carriers for oral delivery of protein-type drugs.

Microfluidic Production of Polymeric Core-Shell Microspheres for the Delayed Pulsatile Release of Bovine Serum Albumin as a Model Antigen.

For many vaccines, multiple injections are required to confer protective immunity against targeted pathogens. These injections often consist of a primer administration followed by a booster administration of the vaccine a few weeks or months later. A single-injection vaccine formulation that provides for both administrations could greatly improve the convenience and vaccinee’s compliance. In this study, we developed parenterally injectable core-shell microspheres with a delayed pulsatile release profile that could serve as the booster in such a vaccine formulation. These microspheres contained bovine serum albumin (BSA) as the model antigen and poly(dl-lactide-co-glycolide) (PLGA) with various dl-lactide:glycolide monomer ratios as the shell material. Highly monodisperse particles with different particle characteristics were obtained using a microfluidic setup. All formulations exhibited a pulsatile in vitro release of BSA after an adjustable lag time. This lag time increased with the increasing lactide content of the polymer and ranged from 3 to 7 weeks. Shell thickness and bovine serum albumin loading had no effect on the release behavior, which could be ascribed to the degradation mechanism of the polymer, with bulk degradation being the main pathway. Co-injection of the core-shell microspheres together with a solution of the antigen that serves as the primer would allow for the desired biphasic release profile. Altogether, these findings show that injectable core-shell microspheres combined with a primer are a promising alternative for the current multiple-injection vaccines.

Electrospun core-shell nanofibers with encapsulated enamel matrix derivative for guided periodontal tissue regeneration.

The osteogenic effect of a composite electrospun core-shell nanofiber membrane encapsulated with Emdogain® (EMD) was evaluated. The membrane was developed through coaxial electrospinning using polycaprolactone as the shell and polyethylene glycol as the core. The effects of the membrane on the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) were examined using Alizarin Red S staining and qRT-PCR. Characterization of the nanofiber membrane demonstrated core-shell morphology with a mean diameter of ~1 µm. Examination of the release of fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) from core-shell nanofibers over a 22-day period showed improved release profile of encapsulated proteins as compared to solid nanofibers. When cultured on EMD-containing core-shell nanofibers, PDLSCs showed significantly improved osteogenic differentiation with increased Alizarin Red S staining and enhanced osteogenic gene expression, namely OCN, RUNX2, ALP, and OPN. Core-shell nanofiber membranes may improve outcomes in periodontal regenerative therapy through simultaneous mechanical barrier and controlled drug delivery function.

The Early Adhesion Effects of Human Gingival Fibroblasts on Bovine Serum Albumin Loaded Hydrogenated Titanium Nanotube Surface

The soft tissue sealing at the transmucal portion of implants is vital for the long-term stability of implants. Hydrogenated titanium nanotubes (H2-TNTs) as implant surface treatments were proved to promote the adhesion of human gingival fibroblasts (HGFs) and have broad usage as drug delivery systems. Bovine serum albumin (BSA) as the most abundant albumin in body fluid was crucial for cell adhesion and was demonstrated as a normal loading protein. As the first protein arriving on the surface of the implant, albumin plays an important role in initial adhesion of soft tissue cells, it is also a common carrier, transferring and loading different endogenous and exogenous substances, ions, drugs, and other small molecules. The aim of the present work was to investigate whether BSA-loaded H2-TNTs could promote the early adhesion of HGFs; H2-TNTs were obtained by hydrogenated anodized titanium dioxide nanotubes (TNTs) in thermal treatment, and BSA was loaded in the nanotubes by vacuum drying; our results showed that the superhydrophilicity of H2-TNTs is conducive to the loading of BSA. In both hydrogenated titanium nanotubes and non-hydrogenated titanium nanotubes, a high rate of release was observed over the first hour, followed by a period of slow and sustained release; however, BSA-loading inhibits the early adhesion of human gingival fibroblasts, and H2-TNTs has the best promoting effect on cell adhesion. With the release of BSA after 4 h, the inhibitory effect of BSA on cell adhesion was weakened.

A Carbodiimide Cross‐Linked Silk Fibroin/Sodium Alginate Composite Hydrogel with Tunable Properties for Sustained Drug Delivery

AbstractCarbodiimide cross‐linked silk fibroin (SF)/sodium alginate (SA) composite hydrogels with superior stability and tunable properties are developed by varying preparation parameters. SF/SA blend ratio modulation allows to achieve composite hydrogel gelation times of 18–65 min, and rheological analysis shows that the speed of gel formation, the hydrogel network's density, and the hydrogels’ compressive properties are closely related to the blend ratio. The G′ of different hydrogels varies substantially from 28 to 413 Pa, and the hydrogel with higher SF content has a greater stiffness. The composite hydrogels present appropriate porosity of 76.63–85.09% and pore size of 316–603 µm. Hydrogel stability improves significantly after cross‐linking, and substantial swelling occurs due to the hydrophilicity of SA. The 7/3 and 6/4 SF/SA hydrogels are more resistant to degradation in PBS, and cytotoxicity testing confirmed their biocompatibility. For release studies in vitro, two model compounds are used as drug models, tetracycline hydrochloride, and bovine serum albumin (BSA). Different ratios of SF/SA have a greater influence on the release of BSA. This study provides a practical preparation method for flexible SF/SA composite hydrogels, which can help design hydrogels with specific physicochemical properties for different applications, especially drug delivery.

Magnetic dual-responsive semi-IPN nanogels based on chitosan/PNVCL and study on BSA release behavior.

Magnetic thermoresponsive nanogels present a promising new approach for targeted drug delivery. In the present study, bovine serum albumin (BSA) loaded thermo-responsive magnetic semi-IPN nanogels (MTRSI-NGs) were developed. At first poly(N-vinyl caprolactam) (PNVCL) was synthesized by free radical polymerization and then MTRSI-NGs were prepared by crosslinking chitosan in presence of chitosan and Fe3O4. The formation of MTRSI-NGs has been confirmed by FTIR, and the average molecular weight of PNVCL was determined by GPC analysis. Rheological and turbidimetry analysis were used to determine lower critical solution temperature (LCST) of PNVCL and magnetic thermo-responsive nanogels (MTRSI-NGs) around 32 and 37°C, respectively. FE-SEM analysis showed particle size at less than 20nm in the dried state. Dynamic light scattering determined particle size at about 30nm in a swelling state. The analysis of release behavior showed that the BSA release ratio at 40°C was faster than 25°C. The pH release behavior was evaluated at pH 5.5 and 7.4 and showed that the drug release rate at pH 5.5 was more rapid than pH 7.4. The results show MTRSI-NGs are applicable to protein targeted delivery by thermosensitive targeted drug delivery systems.

Diffusion of water and protein drug in 1,4-butanediol diglycidyl ether crosslinked galactomannan hydrogels and its correlation with the physicochemical properties

The aim of the present study was to obtain a better and safer galactomannan-based material for drug release applications. A novel epoxy-crosslinked galactomannan hydrogel (EGH) was prepared from guar gum using 1,4-butanediol diglycidyl ether as a crosslinking agent. The diffusion rate constant of water molecules in freeze-dried EGH positively correlated with water uptake/equilibrium swelling rate (WU/ESR), and the water molecules participated in Fickian diffusion. The ESR, WU/ESR, and bovine serum albumin (BSA) loading capacity of a customized EGH with a crosslinking density of 48.9% were 48.7 ± 0.15 g/g, 95.3%, and 56.4 mg/g, respectively. The release of BSA from freeze-dried EGH was affected by the WU/ESR and the pH; the release equilibrium time was ~40 h at pH 1.2, decreasing to ~24 h at pH 7.4. Furthermore, the cumulative release rate increased from 63.5% to 80.7% and the t50 decreased from 59 to 41 min upon changing from the acidic to basic pH. The release process conformed to the Ritger–Peppas and Hixson–Crowell models, and represented Fickian diffusion and chain relaxation. The EGH showed no cytotoxicity toward HeLa cells. Together, these results demonstrate the properties of a novel galactomannan-based hydrogel that can potentially be employed as a vehicle for drug delivery.

A low molecular weight Zr(IV) metallogel for protein delivery

With an exceptional portfolio of properties such as high water content and cross-linked nature, hydrogels can provide an ideal and compatible environment not only to encapsulate but also to control the delivery of biological therapeutics. However, uncontrollable degradation, release and especially swelling impose limitations on our ability to engineer these gels. Herein a zirconium metallogel is proposed that utilizes zirconyl tetramers as the metal component in conjunction with a nucleic acid (adenine). The variable gel-formation temperature as a simple step of gel formation allows the tuning of gel formation and properties by controlling the adenine-nucleobase interactions. Reconstitution, entrapment, degradation, cytotoxicity, and release of bovine serum albumin (BSA) as a negatively charged macromolecular therapeutic agent were investigated. The controllable and sustained release of BSA, offers a route to new tailorable protein delivery applications.

Effects of Gamma Radiation on the Sterility Assurance, Antibacterial Ability, and Biocompatibility of Impregnated Hydrogel Macrosphere Protein and Drug Release.

Devices and medicines used in the medical field must be sterile. Gamma (γ)-irradiation is commonly used for sterilization because its high rate of penetration ensures uniform sterilization. To confirm that hydrogel macrosphere carriers inherit excellent liquid absorption with no cytotoxicity after γ-irradiation sterilization, investigating whether the physiochemical properties of hydrogel macrospheres differ before and after sterilization is essential. The present study evaluated the influence of the recommended 25-kGy γ-irradiation dose on the physicochemical characteristics and in vitro release of bovine serum albumin and vancomycin (an antibiotic medication) from alginate/gelatin with a w/w ratio of 1/4 crosslinking gel macrospheres. Gel macrosphere properties before and after sterilization were compared according to optical and scanning electron microscopy, infrared spectroscopy analysis, the amino residual crosslinking index, water absorption, degradation, sterility assurance, in vitro drug release, antibacterial ability, and cytotoxicity. The crosslinking index was almost unchanged; however, the γ-irradiation caused in situ hydrogel debonding and recrosslinking, which led to a decrease in the water absorption and increase in the degradation rate of the macrospheres after immersion. The release of gel macrospheres carrying vancomycin did not significantly affect antibacterial ability or biocompatibility after γ-irradiation. Accordingly, we conclude that γ-irradiation is suitable for macrospherical formulation.

Synthesis of xanthan gum/trimethyl chitosan interpolyelectrolyte complex as pH-sensitive protein carrier

Protein delivery journey through gastrointestinal (GI) tract faces many challenges due to its physicochemical instabilities, fugitive half-life, and less absorption efficiency. Herein, the aim is the study of both the encapsulation and in-vitro-release of the bovine serum albumin (BSA) through pHs of GI tract within the green synthesized interpolyelectrolyte complex, which was prepared from biodegradable polymers as XG and TMC-based highly an efficient pH-sensitive protein carrier to solve the drawbacks of the protein delivery through GI tract. The structures of XG/TMC PEC and BSA-loaded PEC were elucidated using different analysis tools like FTIR, FE-SEM, EDX, and XRD techniques. The BSA-loaded and released profiles were determined in pH 1.2 (gastric simulated pH) and pH 7.4 (intestine simulated pH) media. Best BSA-loaded results were obtained with the increase in XG concentration, BSA-loaded concentration, and encapsulation time. Moreover, in vitro BSA release results showed that the amount of BSA released in pH 7.4 was higher than that in pH 1.2 and also went up with the rise within the amount from 12 to 120 h to be 97.9% in pH 7.4 and 29.7% in pH 1.2 at 120 h. Moreover, according to SDS-PAGE technique, the BSA was released in intact form out of the PECs; thus, the encapsulation and released conditions did not affect the structural integrity of BSA structure. Finally, the cytotoxicity study of the prepared PEC showed safe and good biocompatibility properties against the traditional human melanocyte cell line.

A study on chitosan-coated liposomes as a carrier of bovine serum albumin as oral protein drug

The development of protein drug liposomes was limited due to the instability of the structure of liposomes, such as easy aggregation, easy fusion, and drug leakage. The object of this work was to prepare bovine serum albumin (BSA) loaded liposomes (BSA-Lip) using BSA as a protein model drug and then BSA-Lip was further coated with chitosan (CH-BSA-Lip) in order to improve the stability of phospholipid bilayer membrane. It was found that the particle size of BSA-Lip increased after being coated with chitosan and the surface potential changed from negative charge to positive charge due to the electrostatic interaction between liposomes and chitosan. After chitosan coating, the encapsulation efficiency of liposomes also increased due to the interaction between positively charged chitosan and negatively charged BSA. Fourier transform infrared spectroscopy analysis confirmed that BSA was encapsulated into liposomes and chitosan was successfully coated on the surface of liposomes. Transmission electron microscopy showed that the particles were nanosized and spherical. The physical stability and in vitro digestion stability of liposomes were examined by observing the changes of particle size and potential. It was found that chitosan coating enhanced the stability of liposomes significantly. The in vitro release profile of CH-BSA-Lip possessed a slow release behavior, and BSA release was governed by both diffusion and dissolution from phospholipid bilayer.

Sulfur(VI) Fluoride Exchange (SuFEx)-Mediated Synthesis of the Chitosan-PEG Conjugate and Its Supramolecular Hydrogels for Protein Delivery.

Supramolecular hydrogels are considered promising drug carriers in the tissue engineering field due to their versatile nature. Chitosan hydrogels without chemical cross-linkers have low cytotoxicity and good delivery capacity; however, they have lower mechanical properties for injectable hydrogel usage. In this study, we developed novel chitosan derivatives via click chemistry for fabricating supramolecular hydrogels with higher mechanical strength under mild conditions. The chitosan derivative was successfully synthesized by a sulfur fluoride exchange reaction, and the synthesized chitosan-mPEG/Pluronic-F127 (CS-mPEG/F127) interacted with α-cyclodextrin (α-CD) to form a supramolecular hydrogel via a host-guest reaction. The gelation dynamics, hydrogel properties, and bovine serum albumin (BSA) release could be modulated by the concentration ratio of chitosan-mPEG and F127. This supramolecular hydrogel is a promising protein releasing carrier candidate for long term regeneration therapy.

Custom-design of intrinsically antimicrobial polyurethane hydrogels as multifunctional injectable delivery systems for mini-invasive wound treatment

• Infections represent the major obstacle hindering the healing of chronic wounds. • The development of polymers intrinsically antimicrobial reduces the need of antibiotics. • The chemical versatility of polyurethanes results in polymers with ad-hoc properties. • System thermosensitivity allows shape-adaptability and rapid post-injection gelation. • The micellar hydrogel network opens the way to versatile delivery carriers. Effective management of hard-to-close skin wounds is a challenging issue due to several co-morbidities in affected patients. Particularly, infections represent a major obstacle in wound healing. The design of efficient wound treatments thus represents an urgent need. Injectable drug delivery hydrogels with intrinsic antimicrobial and antifungal properties were herein designed for perspective application in the mini-invasive treatment of hard-to-close wounds. First, an amphiphilic polyurethane was synthesized from Poloxamer® 407 macrodiol and N-Boc diethanolamine chain extender (DHP407, M ¯ w =33 kDa). Chain-extension reaction step was optimized to maximize the formation of -NH groups along the polymer chains (4.5 × 10 20 ±1.8 × 10 19 –NH groups/g polymer ), after Boc-caging group removal (D-DHP407). DHP407 and D-DHP407 water-based solutions were thermosensitive with slightly different Critical Micellar Concentration (17.5 μg/mL vs . 19.7 μg/mL) and cluster hydrodynamic diameter (235.6 ± 19.9 nm vs . 260.1 ± 20.5 nm), and similar Critical Micellar Temperature (22.5 °C vs . 23.1 °C). A polyurethane solution concentration (15% w/V) was selected by tube-inverting test and rheological analysis showing injectability, as evidenced by sol-to-gel transition at 27.7 ± 0.6 °C for DHP407 and 29.7 ± 0.6 °C for D-DHP407, within few minutes, at similar gelation kinetics. DHP407 and D-DHP407 hydrogels showed controlled release of Bovine Serum Albumin (BSA) model protein (1 mg/mL), with no burst phenomena. BSA released from DHP407 and D-DHP407 hydrogels at 24 h was 33.7 ± 5.0% and 24.6 ± 1.2%, respectively. D-DHP407 hydrogel was biocompatible and able to support NIH-3T3 cell proliferation. Furthermore, D-DHP407 hydrogel showed intrinsic antifungal and antibacterial activity against C. albicans and Gram-positive S. aureus and Gram-negative E. coli bacteria, injectability and capability to retain shape post-injection, making it promising for future use in the management of hard-to-close skin wounds.

PH-responsive injectable polysaccharide hydrogels with self-healing, enhanced mechanical properties based on POSS

Injectable polysaccharide-based hydrogels are widely employed as drug delivery and tissue engineering materials due to the promising biocompatibility and biodegradability, while the mechanical property of polysaccharide hydrogels still requires to be enhanced much for further applications. In the present work, a family of injectable nanocomposite hydrogels were prepared for the first time through the Schiff base reaction between cationic octa (γ-chloroammoniumpropyl) silsesquioxane (OCAPS), chitosan (CS), and oxidized hydroxypropyl cellulose (HPC). It was found that OCAPS dispersed well in the hydrogels and inhibited the crystallization of CS and HPC, and the resulted nanocomposite hydrogels response pH values by reversible sol-gel transitions, namely as the pH value was less than 4.2, the hydrogels were low viscous solutions; while gelled again in mild and basic conditions. The gelation time of the hydrogels shrank from 80 to 49 s, and the swelling ratio increases from 3.7 to 6.6, along with the increase of OCAPS feed ratio gradually. The incorporation of OCAPS into the system also enhanced the mechanical property of the hydrogels. Compared with the controllable hydrogel without OCAPS, which failed to remain a certain shape for a long time, the nanocomposite hydrogels exhibited an outstanding compression property, and 68.4% of stain, 4.1 kPa of modulus, 97.9 kPa of strength when 40.0 wt% OCAPS was loaded. The rheological investigations suggested that the hydrogels possessed a very stable network, hence a self-healing property. Moreover, the result of Bovine serum albumin (BSA) load and release experiments demonstrated much improved drug load efficiency and cumulative drug release percentage of the nanocomposite hydrogels; the in-vitro degradation and cytotoxicity tests exhibited perfect biodegradability and biocompatibility of the hydrogels. All of these results demonstrate that the OCAPS and polysaccharides based hydrogels endow sound applications in drug carrier and tissue engineering materials.

Redox and pH dual-responsive injectable hyaluronan hydrogels with shape-recovery and self-healing properties for protein and cell delivery

In this work, 3, 3'-dithiobis (propanoic dihydrazide) modified and aldehyde-modified hyaluronic acid were respectively synthesized as precursor solutions to form redox and pH dual-responsive injectable hydrogels through dynamic acylhydrazone and disulfide linkages without exogenous stimulus conditions. The reversible sol-gel transition behavior of hydrogels could be repeated multiple times by adjusting DTT/H2O2 or HCl/TEA. Interestingly, the hydrogels shrank gradually when pH decreased, which improved significantly the storage modulus up to 8.4 times at pH 2. Furthermore, the hydrogel presented acid-switchable shape-recovery characteristics of self-healing by a dynamic recombination of acylhydrazone bonds. Moreover, the osmotic driving force derived from inner and outer concentration difference also affected the characteristic. The controlled release of bovine serum albumin (BSA) encapsulated in this hydrogel could be achieved in vitro under simulated pH/redox intracellular and intercellular microenvironment. This hydrogel could also promote chondrocytes proliferation.

Precise and tunable time-controlled drug release system using layer-by-layer films as erodible coatings.

Unlike conventional drug carriers, time-controlled release systems do not release drug immediately, but start to release drug after a predetermined lag time. Coating a drug-loaded core with an erodible barrier is a valid way to defer drug release, however, the complicated erosion behavior of the erodible coatings makes it difficult to predict and tune the lag time. Herein we proposed that dynamic layer-by-layer films, using hydrogen-bonded poly(ethylene glycol)/tannic acid (PEG/TA) film as an example, are ideal erodible coatings, because their erosion mechanism is clear and simple, and they disintegrate at constant rate. As a proof, we demonstrated that the release of bovine serum albumin (BSA) from BMS spheres can be deferred by PEG/TA coating. More importantly, the lag time can be simply tuned by the thickness of the coating. By mixing bimodal mesoporous silica (BMS) spheres coated with different thickness PEG/TA films, multiple pulse release was achieved. Similar release patterns were also successfully achieved in vivo.

Controlled Release of Therapeutics from Thermoresponsive Nanogels: A Thermal Magnetic Resonance Feasibility Study.

Thermal magnetic resonance (ThermalMR) accommodates radio frequency (RF)-induced temperature modulation, thermometry, anatomic and functional imaging, and (nano)molecular probing in an integrated RF applicator. This study examines the feasibility of ThermalMR for the controlled release of a model therapeutics from thermoresponsive nanogels using a 7.0-tesla whole-body MR scanner en route to local drug-delivery-based anticancer treatments. The capacity of ThermalMR is demonstrated in a model system involving the release of fluorescein-labeled bovine serum albumin (BSA-FITC, a model therapeutic) from nanometer-scale polymeric networks. These networks contain thermoresponsive polymers that bestow environmental responsiveness to physiologically relevant changes in temperature. The release profile obtained for the reference data derived from a water bath setup used for temperature stimulation is in accordance with the release kinetics deduced from the ThermalMR setup. In conclusion, ThermalMR adds a thermal intervention dimension to an MRI device and provides an ideal testbed for the study of the temperature-induced release of drugs, magnetic resonance (MR) probes, and other agents from thermoresponsive carriers. Integrating diagnostic imaging, temperature intervention, and temperature response control, ThermalMR is conceptually appealing for the study of the role of temperature in biology and disease and for the pursuit of personalized therapeutic drug delivery approaches for better patient care.