Sol-gel Transition Temperature Research Articles

Ultrasound-Assisted Extraction of Mango (Mangifera indica) Kernel Starch: Chemical, Techno-Functional, and Pasting Properties

(1) Background: Starch is the main component of mango (Mangifera indica) kernel, making it an alternative to obtain an ingredient from a non-conventional source with potential application in food and other industrial applications; however, reports on the use of new extraction techniques for this material are scarce. The main objective of this research was to evaluate the effect of ultrasound-assisted extraction (UAE) on the yield, chemical, techno-functional, rheological, and pasting properties of starch isolated from a non-conventional source such as a mango kernel. (2) Methods: Different power sonication conditions (120, 300, and 480 W) and sonication time (10, 20, and 30 min) were evaluated along with a control treatment (extracted by the wet milling method). (3) Results: Ultrasound-assisted extraction increases starch yield, with the highest values (54%) at 480 W and 20 min. A significant increase in the amylose content, water-holding capacity, oil-holding capacity, solubility, and swelling power of ultrasonically extracted starches was observed. Similarly, mango kernel starch (MKS) exhibited interesting antioxidant properties. The sol-gel transition temperature and pasting parameters, such as the breakdown viscosity (BD) and the setback viscosity (SB), decreased with ultrasound application; (4) Conclusion: indicating that ultrasound caused changes in physical, chemical, techno-functional, rheological, and pasting properties, depending on the power and time of sonication, so it can be used as an alternative starch extraction and modification technique, for example, for potential application in thermally processed food products such as baked goods, canned foods, and frozen foods.

Thermo-induced physically crosslinked polypeptide-based block copolymer hydrogels for biomedical applications.

Stimuli-responsive synthetic polypeptide-containing block copolymers have received considerable attention in recent years. Especially, unique thermo-induced sol-gel phase transitions were observed for elaborately-designed amphiphilic diblock copolypeptides and a range of poly(ethylene glycol) (PEG)-polypeptide block copolymers. The thermo-induced gelation mechanisms involve the evolution of secondary conformation, enhanced intramolecular interactions, as well as reduced hydration and increased chain entanglement of PEG blocks. The physical parameters, including polymer concentrations, sol-gel transition temperatures and storage moduli, were investigated. The polypeptide hydrogels exhibited good biocompatibility in vitro and in vivo, and displayed biodegradation periods ranging from 1 to 5 weeks. The unique thermo-induced sol-gel phase transitions offer the feasibility of minimal-invasive injection of the precursor aqueous solutions into body, followed by in situ hydrogel formation driven by physiological temperature. These advantages make polypeptide hydrogels interesting candidates for diverse biomedical applications, especially as injectable scaffolds for 3D cell culture and tissue regeneration as well as depots for local drug delivery. This review focuses on recent advances in the design and preparation of injectable, thermo-induced physically crosslinked polypeptide hydrogels. The influence of composition, secondary structure and chirality of polypeptide segments on the physical properties and biodegradation of the hydrogels are emphasized. Moreover, the studies on biomedical applications of the hydrogels are intensively discussed. Finally, the major challenges in the further development of polypeptide hydrogels for practical applications are proposed.

Design of Thymol Loaded Dental In Situ Gels; In Vitro Evaluation

Objetive: The aim of the study was to develop thymol thermosensitive in situ gels based on poloxamers in order to prolong dental contact time, control drug release, and enhance dental bioavailability. Materials and Methods: Poloxamer 188 (P188) and poloxamer 407 (P407) were used in varying amounts to designed the in situ gels. Mucoadhesive excipient, like hydroxypropyl methylcellulose (HPMC), was transferred to the in situ gels to improve the formulation's ability to adhere to biological surfaces. For the created formulations, in vitro drug release, pH, clarity, and sol-gel transition temperature were all evaluated.Results: The all of in situ gels gelation temperatures of the developed formulations range from 33 to 37°C, pH values are around 7, and syringeability is defined as the amount of force necessary to discharge each formulation from a syringe fitted with a 20-gauge needle. The quantities of P407 and HPMC with the preparations, decreasing in vitro burst release while also increasing the viscosity but every in situ gel formulation releases for six hours. Conclusion:The results show that in situ gels containing P407 and P188 show promise for thymol dental application.

A MgFe-LDH Nanosheet-Incorporated Smart Thermo-Responsive Hydrogel with Controllable Growth Factor Releasing Capability for Bone Regeneration.

Although growth factor (GF)-loaded hydrogels have been explored as promising materials in repairing bone defects, it still remains challenging to construct smart hydrogels with excellent gelation/mechanical properties as well as controllable GF releasing capability. Herein, the incorporation of bone morphogenetic protein 2 (BMP-2)-functionalized MgFe-layered double hydroxide (LDH) nanosheets into chitosan/silk fibroin (CS) hydrogels loaded with platelet-derived growth factor-BB (PDGF-BB) to construct a smart injectable thermo-responsive hydrogel (denoted as CSP-LB), which can achieve a burst release of PDGF-BB and a sustained release of BMP-2, for highly efficient bone regeneration is reported. The incorporation of MgFe-LDH in CS hydrogel not only shortens the gelation time and decreases sol-gel transition temperature, but also enhances the mechanical property of the hydrogel. Because of the sequential release of dual-GFs and sustained release of bioactive Mg2+ /Fe3+ ions, the in vitro experiments prove that the CSP-LB hydrogel exhibits excellent angiogenic and osteogenic properties compared with the CS hydrogel. In vivo experiments further prove that the CSP-LB hydrogel can significantly enhance bone regeneration with higher bone volume and mineral density than that of the CS hydrogel. This smart thermo-sensitive CSP-LB hydrogel possesses excellent gelation capability and angiogenic and osteogenic properties, thus providing a promising minimally invasive solution for bone defect treatment.

Injectable Composite Systems of Gellan Gum:Alginate Microparticles in Pluronic Hydrogels for Bioactive Cargo Controlled Delivery: Optimization of Hydrogel Composition based on Rheological Behavior

Due to the high complexity of some treatments, there is a need to develop drug-delivery systems that can release multiple drugs/bioactive agents at different stages of treatment. In this study, a thermoresponsive injectable dual-release system was developed with gellan gum/alginate microparticles (GG:Alg) within a thermoresponsive Pluronic hydrogel composed of a mixture of Pluronic F127 and F68. The increase in F68 ratio and decrease in F127 lead to higher transition temperatures. The addition of the GG:Alg microparticles decreased the transition temperatures with a linear tendency. In Pluronic aqueous solutions (20 wt.%), the F127:F68 ratios of 16:4 and 17:3 (wt.%:wt.%) and the addition of microparticles (up to 15 wt.%) maintained the sol–gel transition temperatures within a suitable range (between 25 °C and 37 °C). Microparticles did not hinder the injectability of the system in the sol phase. Methylene blue was used as a model drug to evaluate the release mechanisms from microparticles, hydrogel, and composite system. The hydrogel delayed the release of methylene blue from the microparticles. The hydrogel loaded with methylene blue released at a faster rate than the microparticles within the hydrogel, thus demonstrating a dual-release profile.

Development of Besifloxacin HCL Loaded Ocular İn Situ Gels; In Vitro Characterization Study

Objective: The aim of this study is to develop in situ gel formulations containing besifloxacin hydrochloride are heat triggered, which are prepared by using different poloxomer and derivatives different polymers that will change the gelling temperature to increase corneal contact time, regulate drug release, improve ocular bioavailability and increase patient compliance increase mucoadhesion.
 Material and Method: Various concentrations of poloxamer 188 (P188) and poloxamer 407 (P407) were used to create the in situ forming gels. To increase the gel's capacity for bioadhesion, mucoadhesives such hydroxypropylmethyl cellulose (HPMC) or hydroxyethyl cellulose (HEC) were included in the formulations. Drug release in vitro, sol-gel transition temperature, rheological behavior, pH, clarity, and mucoadhesion force were all assessed for the produced formulations. 
 Result and Discussion: The developed formulations' gelation temperatures ranged from 29 to 35°C. The preparations' viscosity and mucoadhesion force increased with increasing P407, HPMC, and HEC concentrations. Besifloxacin HCl forms in situ gel formulas with K1, K2, K3, and K6 suited for mucoadhesion characteristics, gelation temperature, and viscosity. These formulations exhibit pseudoplastic flow. Increasing polymer concentrations resulted in a reduction in the burst release of the formulations. However, at the end of 6 hours, drug release was finished in all formulations. The results show that in situ gels containing P407 and P188 show promise for besifloxacin HCl application

Thermosensitive system formed by poloxamers containing carvacrol: An effective carrier system against Leishmania amazonensis

The drugs used in the treatment of leishmaniasis show problems concerning side effects and toxicity. As a result, the search for new actives is necessary, and natural products like carvacrol - 5-isopropyl-2-methylphenol, become a relevant alternative. To enable the use of carvacrol as an antileishmanial agent, thermosensitive hydrogels were developed from poloxamer triblock copolymers 407 (P407) and 188 (P188). Carvacrol-free and carvacrol-containing hydrogels were obtained from P407 alone and from the mixture of P407 and P188. The hydrogels were subjected to Differential scanning calorimetry, Small-angle X-ray scattering, Scanning electron microscopy, and Rheology analysis. The activity of hydrogels and carvacrol isolated against promastigotes and intracellular amastigotes of Leishmania amazonensis and their cytotoxicity in mammalian cells was determined. The sol-gel transition temperature for the binary hydrogel containing carvacrol (HG407/188CA) was 37.04 ± 1.35 °C. HG407/188CA presented lamellar structure at temperatures of 25 °C and 37 °C. HG407/188CA and carvacrol presented IC50 against Leishmania amazonensis promastigotes of 18.68 ± 1.43 µg/mL and 23.83 ± 3.32 µg/mL, respectively, and IC50 against Leishmania amazonensis amastigotes of 35.08 ± 0.75 µg/mL and 29.32 ± 0.21 µg/mL, respectively. HG407/188CA reduced the toxicity of carvacrol in all mammalian cells evaluated, raising the CC50 in murine peritoneal macrophages from 40.23 ± 0.21 µg/mL to 332.6 ± 4.89 µg/mL, obtaining a Selectivity Index (SI) of 9.5 against 1.37 of the isolated carvacrol. HG407/188CA provided higher selectivity of carvacrol for the parasite. Thus, the binary hydrogel obtained may enable the use of carvacrol as a potential antileishmanial agent.

κ-Carrageenan Associated with Fructose/Glycerol/Water LTTM: Toward Natural Thermosensitive Physical Gels

κ-Carrageenan was combined to a natural low-transition temperature mixture composed of fructose, glycerol, and water in a 1:1:5 molar ratio (FGW) to generate fully biobased physical gels through a simple method. The resulting gels can be easily prepared in various shapes. As for their hydrogel analogues, the rheological characterization of FGW-based samples evidenced thermosensitive gelation, attributed to the formation of aggregated H-bonded helices composed of κ-carrageenan chains. FGW-based gels exhibit a gel–sol transition temperature (Tg/s) higher than the one of hydrogels with recoverable and reversible viscoelastic properties upon successive heating/cooling cycles. SAXS analysis revealed a more extended conformation of chains in FGW that leads to more physical cross-linking junction zones within the materials. Such peculiar spatial internal organization provides a mechanical reinforcement demonstrated by compression tests. In conclusion, the use of the FGW solvent allows for designing κ-carrageenan physical gels with enhanced thermal and mechanical properties.

Liquid-Liquid Phase-Separated Hydrogel with Tunable Sol-Gel Transition Behavior as a Hotmelt-Adhesive Postoperative Barrier.

Postoperative barriers have been widely used to prevent adhesions. However, there are currently few barriers that satisfy clinical requirements, such as tissue adhesion, operability, and biocompatibility. Inspired by the adhesion system of living organisms, we report a liquid-liquid phase-separated hydrogel as a single-syringe hotmelt-type postoperative barrier. Mixing polyethylene glycol with gelatin formed liquid-liquid phase-separated hydrogels through segregative liquid-liquid phase separation. Incorporation of a liquid-liquid phase-separated system into gelatin can enhance the sol-gel transition temperature to give a hotmelt-adhesive property to hydrogels. Hotmelt-adhesive hydrogels became a sol phase and cohered into tissue gaps when warmed and solidified at body temperature to adhere to soft tissues. The hydrogels exhibited tissue adhesion to large intestine tissues and showed improved mechanical strength, gelation time, and shear-thinning properties. In rat cecum-abdominal adhesion models, it was confirmed that the resulting hydrogels prevented abdominal adhesion and did not prevent tissue regeneration. Hotmelt-adhesive hydrogels with high tissue adhesive properties, operability, and biocompatibility have enormous potential as barriers to prevent postoperative complications.

Development and Characterization of novel bigel of loxoprofen for topical drug delivery

Bigels are unique two-phase systems that have recently been presented as a structured method for active ingredient application. The purposes of the current study were to develop and characterize bigel formulations containing loxoprofen. They have the benefits of both hydrogel and organo-gel. In order to enhance penetration, pluronic lecithin was added to form the organo-gel, and HPMC was added to form the hydrogel, which properly hydrates the stratum corneum. Bigels were produced by mixing hydrogel with organo-gel in the appropriate ratio. pH, viscosity, extrudability, spreadability, and Gel-sol transition temperature were assessed for organo-gel and hydrogel. For the preparation of bigel, formulations O3 from organo-gel and H3 from hydrogel were characterized as optimum formulations. pH, viscosity, extrudability, spreadability, Gel-sol transition temperature, and other properties of the produced bigel were assessed. An 8-hour invitro drug release investigation yielded B1's results, which were 84.77%. B2 demonstrated 92.35 % release, B3 demonstrated 99.18% release, and bigel demonstrated extended-release. Based on evaluation characteristics, formulation B3 was chosen as the optimal formulation. Loxoprofen bigel release kinetics according to the Higuchi model. You can utilize loxoprofen bigel as an extended-release system.
 Keywords: Loxoprofen, (B)Bigel Pluronic F127, (O)Organo-gel, HPMC, Gel-sol, (H)Hydrogel

Incorporation of κ-carrageenan improves the practical features of agar/konjac glucomannan/κ-carrageenan ternary system

Three materials (agar, konjac glucomannan (KGM) and κ-carrageenan) were used to prepare ternary systems, i.e., sol-gels and their dried composites conditioned at varied relative humidity (RH) (33 %, 54 % and 75 %). Combined methods, e.g., scanning electron microscopy, small-angle X-ray scattering, infrared spectroscopy (IR) and X-ray diffraction (XRD), were used to disclose how κ-carrageenan addition tailors the features of agar/KGM/κ-carrageenan ternary system. As affirmed by IR and XRD, the ternary systems with κ-carrageenan below 25 % (agar/KGM/carrageenan, 50:25:25, m/m) displayed proper component interactions, which increased the sol-gel transition temperature and the hardness of obtained gels. For instance, the ternary composites could show hardness about 3 to 4 times higher than that for binary counterpart. These gels were dehydrated to acquire ternary composites. Compared to agar/KGM composite, the ternary composites showed fewer crystallites and nanoscale orders, and newly-formed nanoscale structures from chain assembly. Such multi-scale structures, for composites with κ-carrageenan below 25 %, showed weaker changes with RH, as revealed by especially morphologic and crystalline features. Consequently, the ternary composites with less κ-carrageenan (below 25 %) exhibited stabilized elongation at break and hydrophilicity at different RHs. This hints to us that agar/KGM/κ-carrageenan composite systems can display series applications with improved features, e.g., increased sol-gel transition point.

Development and Evaluation of Puerarin Loaded-Albumin Nanoparticles Thermoresponsive in situ Gel for Ophthalmic Delivery.

PurposePuerarin (PUR) is a major bioactive ingredient extracted from the root of Pueraria lobata (Willd.) Ohwi, which is known as Gegen in traditional Chinese medicine. Conventional PUR ophthalmic dosage forms such as solutions and suspensions have many drawbacks, including-rapid precorneal elimination of the drug mainly due to lacrimal duct drainage. The purpose of this study is to develop a thermal responsive in situ gel system containing PUR-loaded human albumin nanoparticles (PUR-HSA-NPs ISG).MethodsThe system has the required sol-gel phase transition temperature, and therefore can be used for local ocular administration to treat glaucoma. The formulation was evaluated for its sol-gel transition temperature, viscosity and in vitro release. In vivo eye irritation was evaluated in rabbits. In this study, the animal model of glaucoma was used to evaluate the pharmacodynamics of PUR-HSA-NPs ISG in vivo.ResultsMorphologically, the PUR-HSA-NPs ISG exhibited a normal spherical shape with no aggregation or degradation. It had a mean size of 64.8 nm, and the drug-loading and encapsulation efficiency were 7.1%±0.3% and 80.7%±7.4%, respectively. The gelation temperature of the prepared PUR-HSA-NPs ISG thermogelling solutions was 37°C. Meanwhile, the PUR-HSA-NPs ISG showed thixotropic behavior with the downward curve exhibiting lower shear stress values as compared to corresponding points on the upward curve. The pharmacological results showed a continuous reduction of the IOP value for a long time and that the value remained in a lower-level range compared to that in the PUR eye drop group. According to the pharmacodynamic results, the Bcl-2/Bax ratio of the PUR-HSA-NPs ISG group was closest to 1 (0.8798, 24 h), with obvious reduction of tissue cell apoptosis.ConclusionThrough this study, it was found that PUR-HSA-NPs ISG is an ideal ocular drug delivery system. It is hoped that this product could be further promoted for clinical applications in the future.

Poloxamer-Based Hydrogel as Drug Delivery System: How Polymeric Excipients Influence the Chemical-Physical Properties.

Thermogelling amphiphilic block copolymers have been widely investigated in the development of pharmaceutical drug carriers. In particular, thermosensitive gels based on poloxamer 407 (P407) have great potential for periodontal disease treatment, thanks to their ability to be liquid at room temperature and become viscous gels at body temperature. However, some problems, related to short in situ residence time, reduce their feasible clinical use. Thus, in order to improve the effective applicability of these materials, we studied how P407 thermogels are affected by the pH and by the inclusion of different hydrophilic polymers, used as excipients for increasing the gel stiffness. For this scope, a complete chemical-physical characterization of the synthesized gels is provided, in terms of determination of sol-gel transition temperature, viscosity and erosion degree. The data are correlated according to a statistical multivariate approach based on Principal Component Analysis and their mucoadhesion properties are also tested by Tapping mode-Atomic Force Microscopy (TM-AFM) imaging. Finally, we studied how the different P407 formulations are able to influence the release pathway of two antibacterial drugs (i.e., chlorhexidine digluconate and doxycycline hyclate) largely used in oral diseases.

Impact of Salt on Thermal Stability and Dose Response of the Fricke-XO-Pluronic F-127 3D Radiotherapy Dosimeter.

Fricke-XO-Pluronic F-127 has recently been proposed as a 3D dosimeter for radiotherapy. It contains the typical ingredients of the Fricke ionizing radiation dosimeter, which are embedded in a physical gel of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (Pluronic F-127). The main reactions upon irradiation are the conversion of Fe+2 to Fe+3 and the formation of a colored complex with XO ([XO-Fe]+3). The study attempts to optimize the dosimeter in terms of its solution-to-gel transition temperature. In order to lower this temperature, the use of NaCl salt has been proposed. The new composition was characterized in order to obtain information on its thermal performance, storage stability, dose response to irradiation with a medical accelerator emitting different types of radiation, and tissue equivalence. The results obtained show an improvement in the sol-gel transition temperature and dose sensitivity compared to the composition without NaCl and broaden the knowledge of the Fricke-XO-Pluronic F-127.

Solid dipersions included in poloxamer hydrogels have favorable rheological properties for topical application and enhance the in vivo antiinflammatory effect of ursolic acid

Ursolic acid (UA) solid dispersions (SD) formulated into poloxamer-hydrogels were prepared for local treatment of skin inflammations. The hydrogel physico-chemical properties were evaluated, including rheology, in vitro drug permeation and cytotoxicity. The anti-inflammatory activity of the systems was investigated using the animal model of croton oil-induced ear edema. The formulations demonstrated a pseudoplastic behavior and elastic properties (G’ > G”). SDs in hydrogels demonstrated less resistance to flow, an increase in the sol-gel transition temperature and a decrease in G′ followed by an increase in G″ when compared to the hydrogel obtained only in NaCl solution. Bioadhesion and texture properties proved the formulations were suitable for topical application. Hydrogels controlled the diffusion process of the drug within the polymeric network, due to the higher viscosity of this systems. The permeability studies showed that the formulations composed of d-α-tocopheryl polyethylene glycol 1000 succinate provided greater UA diffusion through the skin. The anti-inflammatory effect of UA-SDs was significantly improved when formulated in poloxamer hydrogels, with the ability to inhibit 41.87% and 56.64% of edema when compared to the group of animals that did not receive treatment (negative control). These results indicate the advantages of UA-loaded SDs incorporated into hydrogel for topical treatment of inflammatory skin disorders.

Controlling self-assembly of co-polypeptide by block ratio and block sequence

Block ratio and block sequence of polypeptide influenced the self-assembly of copolymer significantly. Tuning self-assembly to form various nanostructures with different properties through molecular design was a rather feasible strategy. Triblock copolymers based on poly( l -alanine) (PA), poly( l -valine) (PV) and poly (ethylene glycol) (PEG) with various block ratio and block sequence were synthesized. The number of amino acid residues was kept at 10. The sol-gel transition behavior, self-assemble nanostructure, secondary structure of the copolymers in aqueous solution were investigated to reveal that PA block between PEG and PV segment interfered the β-sheet structure, resulting in the reduced or increased sol-gel transition temperature or precipitation depended on the block ratio of PA and PV. Shorter PA or PV block displayed more significant influence on sol-gel transition. Interestingly, PV block between PEG and PA segment induced the formation of more stable β-sheet stacking structures, leading to sol-gel transition at higher temperature. PEG dehydration and the enhancement of ordered structure with temperature rising caused the sol-gel transition of these copolymers. We concluded herein that disordered structure in co-polypeptide can enhance thermo-sensitivity. • Conformation of synthesized non-natural polypeptides based on side-chain design. • Block sequence of non-natural polypeptides affected sol-gel transition. • Shorter peptide block influenced more significantly on sol-gel transition. • Less hydrophobic and weaker steric hindrance block at the tail enhanced the stability of nanostructures. • Disordered structure in co-polypeptide enhanced thermo-sensitivity.

A tunable gelatin-hyaluronan dialdehyde/methacryloyl gelatin interpenetrating polymer network hydrogel for additive tissue manufacturing

Methacryloyl gelatin (GelMA) is a versatile material for bioprinting because of its tunable physical properties and inherent bioactivity. Bioprinting of GelMA is often met with challenges such as lower viscosity of GelMA inks due to higher methacryloyl substitution and longer physical gelation time at room temperature. In this study, a tunable interpenetrating polymer network (IPN) hydrogel was prepared from gelatin-hyaluronan dialdehyde (Gel-HDA) Schiff’s polymer, and 100% methacrylamide substituted GelMA for biofabrication through extrusion based bioprinting. Temperature sweep rheology measurements show a higher sol-gel transition temperature for IPN (30 °C) compared to gold standard GelMA (27 °C). Furthermore, to determine the tunability of the IPN hydrogel, several IPN samples were prepared by combining different ratios of Gel-HDA and GelMA achieving a compressive modulus ranging from 20.6 ± 2.48 KPa to 116.7 ± 14.80 KPa. Our results showed that the mechanical properties and printability at room temperature could be tuned by adjusting the ratios of GelMA and Gel-HDA. To evaluate cell response to the material, MC3T3-E1 mouse pre-osteoblast cells were embedded in hydrogels and 3D-printed, demonstrating excellent cell viability and proliferation after 10 d of 3D in vitro culture, making the IPN an interesting bioink for the fabrication of 3D constructs for tissue engineering applications.

NIR Responsive Injectable Nanocomposite Thermogel System Against Osteosarcoma Recurrence.

Compared to traditional postoperative radiation and chemotherapy, immune checkpoint blockade (ICB) therapy demonstrates superiority by provoking own immune system to cure cancer completely even for some terminally ill patients. However, systemic administration of ICB is liable to cause severe immunity inflammation or immune storm. Here, an injectable, near infrared (NIR) responsive, multifunctional nanocomposite thermogel as a local ICB delivery system for cancer postsurgical therapy is proposed. By copolymerization of thermosensitive and zwitterionic monomer, the injectable thermogel with adjustable sol-gel transition temperature is obtained. Afterward, combined with functional mesoporous nanoparticles, the platform can absorb NIR light and transfer it into heat. The generated heat will promote retro Diels-Alder (D-A) reaction to degrade coating layer on nanoparticle, achieving NIR controlled ICB release. Furthermore, the local ICB delivery system is applied on an osteosarcoma postsurgical recurrence model and results indicate the platform with favorable biocompatibility can avoid early leakage of cargos and greatly increase drug content at tumor site. Besides, long-term controlled ICB release of the system effectively improves the amount of active T cells, resulting in excellent antitumor recurrence effect. Overall, this work suggests the local injectable nanocomposite thermogel is expected to be a promising tool for cancer postoperative therapy.

Synthesis of low-molecular-weight gel with tunable gel-sol transition temperature for thermo-sensitive drug controlled release

A phenylboronic acid (PBA)-based gelator was synthesized, and host-guest low-molecular-weight gel (LMWG) was fabricated by the inclusion complexes (ICs) of the gelator and β-cyclodextrin (β-CD). Translucent gel consisting of nanofiber or nanobelt (60–430 nm wide) was obtained with low critical gelation concentration (CGC) of 2.9 mg/mL (0.36 wt%). The gel-sol transition temperature (Tgel) of the IC gel could be regulated from 37.5 °C to 44.9 °C by different inclusion ratio of gelator and β-CD. And the rheological properties exhibited the rapid recovery of the sol, the gel was re-formed in 2.5 min at 37 °C, and fully restored the initial storage modulus (G’). This tunable gel-sol-gel transition has been applied in thermo-sensitive controlled release of naproxen for tumor fever. Naproxen (16.7 μg•mL−1•min−1) was released from the drug-loaded gel (Loading Efficiency = 8.3%) when heated at 38.5 °C, and the release process terminated when the sol reconverted into gel at 37 °C, and it was achieved again when the gel converted to sol at 38.5 °C. Both the blank and drug-loaded gel could gellated rapidly after subcutaneous injection. The stability of gel was greatly improved to 102 h by the salts' induce, and the gel-sol transition was also controlled by vary kinds of salts and salt concentration.

L-Proline adsorbed oxygen-loaded nanobubbles in-situ gel for wound healing

AimWound healing is a natural physiological process that restores the damaged layers of the skin by the migration and proliferation of fibroblasts. This present research work aimed to develop a nanoformulation gel of oxygen and L-proline to offer a synergistic effect on the wound healing process for better patient compliance and protection from cross-infections. Main methodsThe nanobubbles were prepared using the gas entrapment method, followed by cold addition for the synthesis of in-situ gel and further characterized by different parameters like dissolved oxygen level, particle size and zeta potential, in-vitro, ex-vivo release and animal studies. Key findingsL-Proline oxygen nanobubbles in-situ gel formulation was prepared by incorporating oxygen concentration of 15.5 mg/L at pH 5.6. The concentration of dissolved oxygen was stabilized for 6 h and displayed synergistic effects with L-proline at the sol-gel transition temperature. In-vivo studies demonstrated complete wound healing in 21 days and 27 days for oxygen nanobubble with L-proline and control group, respectively. SignificanceThis controlled release nanoformulation showed a combinational effect of oxygen and L-proline for reducing the frequency of application compared to the marketed formulation.