Carrier For Release Research Articles

Development of antioxidant active packaging films with slow release properties incorporated with tea polyphenols-loaded porous starch microcapsules

Slow release active packaging films can realize the sustained release of active agents and prolong the shelf life of food. For this aim, a novel slow release active polyvinyl alcohol (PVA) film was developed by using solution casting method. With porous starch loaded with tea polyphenols (PSTP) as core material and maltodextrin (MD) as wall material, PSTP@MD microcapsules were prepared using freeze drying method and used as slow release carrier of tea polyphenols (TP) in the active films. The interactions between PSTP@MD microcapsules and PVA molecular chains were physical interactions. In addition, the relative crystallinity of the slow release active films was reduced to 23.74 %. The addition of PSTP@MD microcapsules can enhance the ductility of active films and reduce the water content and swelling degree of active films by 46.74 % and 54.38 %, respectively. Moreover, the thermal stability, water vapor and ultraviolet barrier properties of active films were promoted. The transparency and antioxidant activity of active films was high, and the radical scavenging activity of active films was 58 %. The encapsulation of TP with PSTP@MD microcapsules can realize the slow release of TP. The slow release active films had antioxidant activity and sustained release properties, which could be used as an active packaging film to extend the shelf life of food.

Density Functional Theory Interaction Study of a Polyethylene Glycol-Based Nanocomposite with Cephalexin Drug for the Elimination of Wound Infection.

In this paper, density functional theory (DFT) simulations are used to evaluate the possible use of a graphene oxide-based poly(ethylene glycol) (GO/PEG) nanocomposite as a drug delivery substrate for cephalexin (CEX), an antibiotic drug employed to treat wound infection. First, the stable configuration of the PEGylated system was generated with a binding energy of −25.67 kcal/mol at 1.62 Å through Monte Carlo simulation and DFT calculation for a favorable adsorption site. The most stable configuration shows that PEG interacts with GO through hydrogen bonding of the oxygen atom on the hydroxyl group of PEG with the hydrogen atom of the carboxylic group on GO. Similarly, for the interaction of the CEX drug with the GO/PEG nanocomposite excipient system, the adsorption energies are computed after determining the optimal and thermodynamically favorable configuration. The nitrogen atom from the amine group of the drug binds with a hydrogen atom from the carboxylic group of the GO/PEG nanocomposite at 1.75 Å, with an adsorption energy of −36.17 kcal/mol, in the most stable drug–excipient system. Drug release for tissue regeneration at the predicted target cell is more rapid in moist conditions than in the gas phase. The solubility of the suggested drug in the aqueous media around the open wound is shown by the magnitude of the predicted solvation energy. The findings from this study theoretically validate the potential use of a GO/PEG nanocomposite for wound treatment application as a drug carrier for sustained release of the CEX drug.

Pectin functionalized metal-organic frameworks as dual-stimuli-responsive carriers to improve the pesticide targeting and reduce environmental risks

Encapsulation of active ingredients into intelligent response controlled release carriers has been recognized as a promising approach to enhance the utilization efficiency and reduce the environmental risks of pesticides. In this work, an intelligent redox and pectinase dual stimuli-responsive pesticide delivery system was constructed by bonding pectin with metal-organic frameworks (FeMOF nanoparticles) which were loaded with pyraclostrobin (PYR@FeMOF-pectin nanoparticles). The successful fabrication of PYR@FeMOF-pectin nanoparticles was proved by a series of physicochemical characterizations. The results indicated that the loading capacity of PYR@FeMOF-pectin nanoparticles for pyraclostrobin was approximately 20.6%. The pectin covered on the surface of PYR@FeMOF nanoparticles could protect pyraclostrobin from photolysis and improve their spreadability on rice blades effectively. Different biological stimuli associated with Magnaporthe oryzae could trigger the release of pyraclostrobin from the pesticide-loaded core-shell nanoparticles, resulting in the death of pathogens. The bioactivity survey determined that PYR@FeMOF-pectin nanoparticles had a superior fungicidal activity and a longer duration against Magnaporthe oryzae than pyraclostrobin suspension concentrate. In addition, the FeMOF-pectin nanocarriers showed no obvious phytotoxicity and could enhance the shoot length and root length of rice plants. More importantly, PYR@FeMOF-pectin nanoparticles had an 8-fold reduction in acute toxicity to zebrafish than that of pyraclostrobin suspension concentrate. Therefore, the dual-responsive FeMOF-pectin nanocarriers have great potential for realizing site-specific pesticide delivery and promoting plant growth.

Development of a Self‐Adhesive Oleogel Formulation Designed for the Slow Release of Semiochemicals

AbstractOleogels have been widely studied as delivery matrices for lipophilic compounds. Despite their potential, oleogels are underexplored for the formulation and release of semiochemicals for insect behavior manipulation strategies. An ethylcellulose‐candelilla wax‐oleogel as a suitable carrier for the slow release of volatile semiochemicals, employing the sesquiterpene β‐caryophyllene as a model substance is presented. A current drawback of ethylcellulose oleogels is the high temperature needed during the oleogel preparation procedure, leading to excessive volatilization of the active compounds. Reducing the gelling temperature from 104.8 to 66.9 °C and, thus, the volatile addition temperature by addition of the softener octyldodecanol results in 95.28% entrapment efficiency. Experimental results demonstrate release modifiability by tailoring the matrix crystalline state due to candelilla wax addition. Furthermore, a method is established for analyzing the self‐adhesive properties of the gel on plant leaves. In addition, the gel's self‐adhesive properties employed on apple leaves are synergistically affected by oil leakage and gel stiffness. Olfactometer experiments showed that the formulation is able to enhance the attractiveness of aphid‐infested plants for parasitic wasps. The present study provides a novel matrix‐type semiochemical formulation based on non‐toxic, biobased and biodegradable materials and will contribute to the establishment of oleogels as delivery systems for semiochemicals.

Fumarate‐co‐PEG‐co‐sebacate photopolymer and its evaluation as a drug release system

AbstractFumarate‐co‐PEG‐co‐sebacates with different fumaric/sebacic acid ratios are prepared by a simple thermal polycondensation reaction using p‐toluensulfonic acid as catalyst. These polymeric precursors are purified by washing with an appropriate organic solvent and the dried materials were photocured to yield elastic films under mild conditions. The properties of polymeric precursors and elastic materials are studied in detail and correlated with fumaric acid/sebacic acid ratios used in the thermal esterification reactions. It is shown that a higher amount of sebacic in the starting polymer leads to softer final film materials, with lower Tg and G' values, which also show higher degradation rates in vitro. Finally, the films are also evaluated as drug release carriers for in vitro release of Cephalexin and Progesterone. The results obtained in these studies indicate that the careful tailoring of the fumaric acid/sebacic acid ratio in the esterification reaction allows to finely tune the thermal, mechanical a degradation properties of the final cross‐linked elastic films.

Covalent Organic Framework (COF): A Drug and Carrier to Attenuate Retinal Ganglion Cells Death in an Acute Glaucoma Mouse Model

Purpose: We aim to investigate the use of covalent organic framework (COF) nanoparticles in the local treatment of glaucoma, both as a means of protecting retinal ganglion cells (RGCs), and as a carrier for delayed release of the medication rapamycin following a single intravitreal injection. Methods: a water-dispersible COF, and a COF-based nanoplatform for rapamycin release (COF-Rapa) was constructed. C57BL/6J mice were randomly divided into four groups: intravitreal injection of 1.5 µL normal saline (NS), COF (0.67 ng/µL), rapamycin (300 µM) or COF-Rapa (0.67 ng/µL-300 µM), respectively. The ischemia–reperfusion (I/R) model was established to mimic high intraocular pressure (IOP)-induced retinal injury in glaucoma. Labeling of RGCs by Fluoro-Gold and retinal electroretinogram were used to evaluate retinal function. Immunohistochemistry and Western blotting analyses of retinas were performed. Results: COF nanoparticles were delivered in vitro and in vivo. Six weeks after the COF injection, the number of RGCs was unaffected. In addition, the number of RBPMS-positive RGCs, GFAP-positive astrocytes and Iba1-positive microglia did not differ from the normal control. COF could effectively reduce RGCs death, improve phototransduction function and alleviate the overactivation of microglia compared to NS control after retinal I/R injury. Within six weeks, the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway in the retinas could be inhibited by a single intravitreal injection of COF-Rapa. Compared with single COF administration, COF-Rapa significantly reduced the inflammatory reaction after retinal I/R injury. Conclusions: COF may act as both an RGC protection agent and a carrier for prolonged rapamycin release. This research may lead to the development of novel RGC protection agents and drug delivery techniques, as well as the creation of multifunctional COF-based biomaterials for glaucoma retinopathy.

Pectin / chitosan nanoparticle beads as potential carriers for quercetin release

The present work explores the fabrication of pectin/chitosan nanoparticle (PEC/CSNP) beads as nanocarrier encapsulating hydrophobic quercetin overcome solubility and sensitivity problems by ionotropic gelation method. ATR-FTIR studies evidenced the chemical interaction among the drug and the polymer matrix. The surface morphology of the unloaded and quercetin loaded PEC/CSNPs beads were characterized by scanning electron microscopy. The nanoparticulate beads had higher % encapsulation efficiency (EE) that varied between 34% and 56.2% and loading capacity (LC) from 12% to 24.4%. In vitro drug release study of the beads showed a capacity to release quercetin in a sustained release pattern. The swelling behavior of the beads demonstrated an increase in mechanical resistance due to the presence of pectin in the formulation at low pH. The association of quercetin and the polymeric nanoparticles induces a synergistic effect that improved the beads antibacterial properties. The antioxidant potency of quercetin was enhanced by 71% after encapsulation and hemolysis studies showed good blood compatibility. The in vitro cytotoxicity of blank and Q-PEC/CSNP beads showed cell viability above 80% on the L929 cell line. These results suggested that the PEC/CSNPs beads can be suitably an effective drug delivery vehicle emphasizing the stability of chitosan nanoparticles in the gastrointestinal tract where pH is low.

Mechanistic insight into impact of clay on compressive elasticity of poly(N-alkyl acrylamide)/Laponite-based nanocomposite cryo-beads

Relationship between formation pathway and Hertzian elasticity of poly(N-isopropylacrylamide-co‑sodium acrylate)/Laponite® XLG, P(NIPA-NaA)/LAP, based nanocomposite cryo-beads was evaluated. Millimeter-sized nanocomposite cryo-beads were prepared by combination of dropwise freezing into cryogenic liquid (DFLC) method with sedimentation cryogelation method. pH-sensitive 3D-templete was formed by conducting free-radical crosslinking cryopolymerization of NIPA and NaA in the presence of synthetic hectorite Laponite® XLG as inorganic crosslinker and N,N′-methylenebis(acrylamide) as chemical crosslinker. The effects of network template, ionic comonomer, inorganic clay incorporation, pH- and ionic strength of swelling medium on the swelling and elasticity were evaluated as a function of bead size. The deformability of swollen cryo-beads was investigated using Hertzian elasticity. The crosslink density and Hertz modulus of nanocomposite beads vary with the droplet size and the polymer spheres with low crosslink density tend to absorb more water. In DFLC method, the desired sphere size and swelling can be adjusted by selecting the needle size used for dripping. The swelling degree increased significantly as the size of nanocomposite cryo-beads increased. At a fixed swelling ratio, the cylindrical nanocomposite cryogels exhibited greater elastic moduli and crosslink density than that of spherical gels. Correlation of elastic modulus of cryo-beads with swelling and cross-linked polymer concentration predicted a higher scaling exponent than the classical estimate for swelling in good solvents. It was investigated how the presence of 30 mol% pH-sensitive anionic comonomer NaA in the structure of all nanocomposite gels affects their pH-dependent swelling behavior. At pH < 5.7, the gels exhibited a lower swelling ratio, whereas at pH > 6.6 they tended to swell and followed second-order swelling kinetics by Fickian diffusion. When pH of swelling medium was alternately changed, all gels exhibited a pH-switch and swelling rate was two times higher than shrinkage rate. By investigating the effect of KCl, NaCl and K2CO3 on the swelling of cryobeads, it was determined how the salt cation changes the electrostatic repulsion between network charges. Nanocomposite cryo-beads showed fast pH-responsiveness and immediately reabsorbed the water they lost due to pH change, therefore, they can be designed as drug release carriers by pH-switching modulation.

DNA-Liposome Hybrid Carriers for Triggered Cargo Release.

The design of simple and versatile synthetic routes to accomplish triggered-release properties in carriers is of particular interest for drug delivery purposes. In this context, the programmability and adaptability of DNA nanoarchitectures in combination with liposomes have great potential to render biocompatible hybrid carriers for triggered cargo release. We present an approach to form a DNA mesh on large unilamellar liposomes incorporating a stimuli-responsive DNA building block. Upon incubation with a single-stranded DNA trigger sequence, a hairpin closes, and the DNA building block is allowed to self-contract. We demonstrate the actuation of this building block by single-molecule Förster resonance energy transfer (FRET), fluorescence recovery after photobleaching, and fluorescence quenching measurements. By triggering this process, we demonstrate the elevated release of the dye calcein from the DNA–liposome hybrid carriers. Interestingly, the incubation of the doxorubicin-laden active hybrid carrier with HEK293T cells suggests increased cytotoxicity relative to a control carrier without the triggered-release mechanism. In the future, the trigger could be provided by peritumoral nucleic acid sequences and lead to site-selective release of encapsulated chemotherapeutics.

In vitro and in vivo biocompatibility of decellularized cellulose scaffolds functionalized with chitosan and platelet rich plasma for tissue engineering applications

This study describes the fabrication of cellulose scaffold (CS) and cellulose-chitosan (CS/CHI) scaffolds from the immature endosperm of Borassus flabellifer (Linn.) (BF) loaded with platelet rich plasma (PRP). Thus, developed scaffolds were evaluated for their physicochemical and mechanical behavior, growth factor release and biological performance. Additionally, in vivo response was assessed in a sub cutaneous rat model to study vascularization, host inflammatory response and macrophage polarization. The results of this study demonstrated that CS and CS/CHI scaffolds with PRP demonstrated favorable physiochemical and morphogical properties. The scaffold groups CS-PRP and CS/CHI-PRP were able to release growth factors in a well sustained manner under physiological conditions. The presence of PRP in cellulosic scaffolds did show significant differences in their behavior when investigated under in vitro studies, where the release of diverse cytokines improved the cellular proliferation and differentiation of osteoblasts. Finally, the PRP enriched scaffolds when studied under in vivo conditions showed increased angiogenesis and re-epithelialization with adequate collagen deposition and tissue remodeling. Our results suggest that besides the conventional carrier systems, this new-generation of plant-based cellulosic scaffolds with/without any modification can serve as a suitable carrier for PRP encapsulation and release, which can be used in numerous tissue regenerative therapies.

Electrospun fibers as carriers for topical drug delivery and release in skin bandages and patches for atopic dermatitis treatment.

The skin is a complex layer system and the most important barrier between the environment and the organism. In this review, we describe some widespread skin problems, with a focus on eczema, which are affecting more and more people all over the world. Most of treatment methods for atopic dermatitis (AD) are focused on increasing skin moisture and protecting from bacterial infection and external irritation. Topical and transdermal treatments have specific requirements for drug delivery. Breathability, flexibility, good mechanical properties, biocompatibility, and efficacy are important for the patches used for skin. Up to today, electrospun fibers are mostly used for wound dressing. Their properties, however, meet the requirements for skin patches for the treatment of AD. Active agents can be incorporated into fibers by blending, coaxial or side-by-side electrospinning, and also by physical absorption post-processing. Drug release from the electrospun membranes is affected by drug and polymer properties and the technique used to combine them into the patch. We describe in detail the in vitro release mechanisms, parameters affecting the drug transport, and their kinetics, including theoretical approaches. In addition, we present the current research on skin patch design. This review summarizes the current extensive know-how on electrospun fibers as skin drug delivery systems, while underlining the advantages in their prospective use as patches for atopic dermatitis. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Fabrication of phenylalanine amidated pectin using ultra-low temperature enzymatic method and its hydrogel properties in drug sustained release application

In this study, pectin was modified with phenylalanine by ultra-low temperature enzymatic method to improve its gel properties. The grafting ratio of phenylalanine amidated pectin was studied under different reaction conditions. The highest value (29.21 %) was reached a reaction temperature of −5 °C and time of 12 h. Further analysis indicated that phenylalanine and high methoxyl pectin combined at the solid-liquid two phase interface under the catalysis of papain to form phenylalanine amidated pectin. Moreover, the physicochemical properties of pectin hydrogel and its feasibility as a sustained-release drug carrier were discussed. The results showed that phenylalanine amidated pectin can form hydrogel with a certain strength under acidic conditions, and there is no need to add a lot of soluble solids and divalent cations. Besides, the phenylalanine amidated pectin hydrogel as a sustained release carrier of drugs showed more sustained and complete drug release.

Design and evaluation of redox responsive disulfide containing resveratrol loaded nanocarrier anti-cancer activity in the MDA-MB-231 cell line

Redox-responsive resveratrol (RES)-loaded nanocarrier (R-NC) was fabricated using stearic acid-disulfide-methoxy poly (ethylene glycol) (SA-SS-mPEG) as a potential carrier for stimuli-responsive drug release. The synthesized redox responsive SA-SS-mPEG was evaluated through FTIR, 1H NMR, DTA/TGA and XRD analysis and was further utilized to develop R-NC by nanoprecipitation method. The NC was characterized for physicochemical properties and its susceptibility to redox and intracellular acidic pH were assessed through alterations in the size of the NC and release of resveratrol from the R-NC in the pH 5 & 7.4 medium with presence or absence of glutathione (GSH). The size of the NC was observed to increase from 140 nm to 1005 nm in the presence of an excessive concentration of GSH/pH 5 medium while showing lesser changes in the absence of GSH and pH 7.4. Drug release profiling of the R-NC confirmed that the presence of GSH in the pH 5 medium influenced the rapid release of the resveratrol by 89.23 ± 1.03% in 6 h compared to the GSH presence pH 7.4 (79.83 ± 1.15% in 6 h) and GSH free pH 5 & 7.4 medium respectively 59.67 ± 0.78% & 47.22 ± 1.18% in 18 h. R-NC, probably encompassed in cytotoxicity, reduces cancer cell proliferation with apoptotic regulation. Biocompatibility of the NC was confirmed through hemolytic assay, which showed that the NC deliberated safety up to the concentration of 200 µg/mL. Overall results accentuated the suitability of the developed R-NC for stimuli gated redox and pH-responsive drug delivery in the treatment of cancer.

Abstract 304: Effect of paclitaxel stereochemistry on x-ray-triggered release of paclitaxel from CaWO4/paclitaxel-coloaded PEG-PLA nanoparticles

Abstract Head and neck squamous cell carcinoma (HNSCC) is the 8th most common cancer in the United States predominantly affecting people over 65 years of age with an increasing rate of incidence across the world. Current therapies for HNSCC include surgical resection, chemotherapy (CT), and radiotherapy (RT). For locally advanced/unresectable HNSCC, the CT-RT combination (“chemoradiation”) has been shown to be more effective than CT or RT alone, and is currently the standard of care. Intratumoral (IT) chemotherapy-based chemoradiation has the potential to overcome the limitations of conventional systemic CT-RT that severely affects a patient’s quality of life. For realization of maximum benefits from IT CT-RT, our team has developed a radiation-controlled drug release nanoparticle formulation (paclitaxel (PTX) and CaWO4 nanoparticles (CWO NPs) co-encapsulated within a capsule formed by poly(ethylene glycol)-poly (lactic acid) (PEG-PLA), named “PEG-PLA/CWO/PTX NPs”). This unique formulation releases PTX only when it is exposed to X-ray irradiation. We have previously reported that IT-administered PEG-PLA/CWO/PTX NPs stay within the tumor for at least a month, producing significant therapeutic effects in terms of tumor suppression and survival in mouse models of HNSCC. This work demonstrates the effect of PTX stereochemistry on radiation-controlled release of the drug from a nano polymer matrix system (PEG-PLA/CWO/PTX NPs). The stereoisomertic characteristics of PTX products from two different manufacturers (“PTX-S”, and “PTX-B”) were analyzed by Raman spectroscopy, circular dichroism and 2D HMQC/NOESY NMR measurements. In their unencapsulated (free) state, PTX-S and PTX-B were comparable in their ability to kill cancer cells in vitro. However, they were found to be significantly different in water solubility; PTX-S (water solubility ≈ 4.69 μg/mL) is about 19 times more water soluble than PTX-B (water solubility ≈ 0.25 μg/mL). This difference in water solubility was found to cause a large difference in X-ray-triggered release kinetics of the PTX loaded within the PEG-PLA/CWO/PTX NPs in both in vitro and in vivo environments; PTX-S is released from PEG-PLA/CWO NPs significantly faster upon X-ray irradiation than PTX-B. This difference in release kinetics produced an interesting difference in their time-dependent therapeutic effects; at short times (&amp;lt; 1 month), concurrent PEG-PLA/CWO/PTX-S NPs produced a greater tumor suppression effect; on the other hand, PEG-PLA/CWO/PTX-B NPs had a longer lasting radio-sensitizing effect. In summary, the stereoisomers of PTX exhibit significantly different PK characteristics when used with controlled release carriers, even though they are pharmacologically indistinguishable in their unformulated form. Citation Format: Kaustabh Sarkar, Sandra Torresgrossa-Allen, Mark P. Langer, Gregory Durm, Sanjeev Narayanan, Bennett D. Elzey, You-Yeon Won. Effect of paclitaxel stereochemistry on x-ray-triggered release of paclitaxel from CaWO4/paclitaxel-coloaded PEG-PLA nanoparticles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 304.

Application of vancomycin-impregnated calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan injectable hydrogels combined with BMSC sheets for the treatment of infected bone defects in a rabbit model

BackgroundThe choice of bone substitutes for the treatment of infected bone defects (IBDs) has attracted the attention of surgeons for years. However, single-stage bioabsorbable materials that are used as carriers for antibiotic release, as well as scaffolds for BMSC sheets, need further exploration. Our study was designed to investigate the effect of vancomycin-loaded calcium sulfate hemihydrate/nanohydroxyapatite/carboxymethyl chitosan (CSH/n-HA/CMCS) hydrogels combined with BMSC sheets as bone substitutes for the treatment of IBDs.MethodsBMSCs were harvested and cultured into cell sheets. After the successful establishment of an animal model with chronic osteomyelitis, 48 New Zealand white rabbits were randomly divided into 4 groups. Animals in Group A were treated with thorough debridement as a control. Group B was treated with BMSC sheets. CSH/n-HA/CMCS hydrogels were implanted in the treatment of Group C, and Group D was treated with CSH/n-HA/CMCS+BMSC sheets. Gross observation and micro-CT 3D reconstruction were performed to assess the osteogenic and infection elimination abilities of the treatment materials. Histological staining (haematoxylin and eosin and Van Gieson) was used to observe inflammatory cell infiltration and the formation of collagen fibres at 4, 8, and 12 weeks after implantation.ResultsThe bone defects of the control group were not repaired at 12 weeks, as chronic osteomyelitis was still observed. HE staining showed a large amount of inflammatory cell infiltration around the tissue, and VG staining showed no new collagen fibres formation. In the BMSC sheet group, although new bone formation was observed by gross observation and micro-CT scanning, infection was not effectively controlled due to unfilled cavities. Some neutrophils and only a small amount of collagen fibres could be observed. Both the hydrogel and hydrogel/BMSCs groups achieved satisfactory repair effects and infection control. Micro-CT 3D reconstruction at 4 weeks showed that the hydrogel/BMSC sheet group had higher reconstruction efficiency and better bone modelling with normal morphology. HE staining showed little aggregation of inflammatory cells, and VG staining showed a large number of new collagen fibres.ConclusionsOur preliminary results suggested that compared to a single material, the novel antibiotic-impregnated hydrogels acted as superior scaffolds for BMSC sheets and excellent antibiotic vectors against infection, which provided a basis for applying tissue engineering technology to the treatment of chronic osteomyelitis.

Foldable/Expandable Gastro-retentive Films Based on Starch and Chitosan as a Carrier For Prolonged Release of Resveratrol.

Resveratrol exerts a number of therapeutic effects, notably antiinflammatory, antioxidant and anti-cancer activities which are beneficial for the treatment of gastric diseases. However, the efficacy of resveratrol is severely limited due to the poor aqueous solubility and rapid metabolism following oral administration. As a result, foldable/expandable devices based on natural polymers merging with solid dispersion technology have been developed to increase the solubility, prolong the gastric residence time, and provide a controlled release therapy of resveratrol. This research aimed to invent foldable/expandable films based on natural polymers, including starch and chitosan, for stomach-specific delivery and prolonged release of resveratrol. The films were prepared by solvent casting using either rice, tapioca, corn starch or pregelatinized corn starch combined with chitosan in different weight to weight ratios. Glycerol was included as a plasticizer. Resveratrol solid dispersions (Res-SD) prepared by solvent evaporation and employing PVP-K30 as a hydrophilic polymer were loaded into the polymeric film, which was subsequently folded prior to insertion in a hard gelatin capsule. The solid dispersions improved the solubility of resveratrol by a factor of 500. All Res-SD loaded film formulations completely unfolded in simulated gastric fluid at 37oC within 10 min. Fluid absorption by the films was influenced by the ratio of amylose and amylopectin in the starch granules, with tapioca starch formulations displaying the highest fluid uptake. Films prepared from pregelatinized corn starch and chitosan resulted in highly efficient delivery of resveratrol, with more than 80%of the content released over a period of 12 hrs. Furthermore, the released polyphenol exhibited cytotoxic activity against human gastric adenocarcinoma cells and anti-inflammatory effects against lipopolysaccharide-stimulated murine, macrophage-like cells. These findings demonstrate the potential of foldable/expandable films based on natural polymers as a promising stomach-specific carrier for improving the treatment of gastric disorders.

Bupivacaine-loaded hydroxypropyl chitin based sponges prepared via a solvent-free process provide long-acting local anesthesia for postoperative pain

Local anesthetics have been extensively used in clinical practice to relieve the postoperative pain of patients. However, due to the short half-life of local anesthetics, a simple injection of local anesthetics cannot provide sufficient anesthetic effect for patients. It is important to develop a new delivery system for local drug administration to achieve an extended anesthetic effect without notable side effects. In this study, bupivacaine hydrochloride (BPV) loaded thermosensitive hydroxypropyl chitin (HPCH) based sponges were prepared via a simple solvent-free process for long-lasting drug release. The HPCH sponge showed good mechanical property to resist external stress and maintain the integrity, which was stronger than the collagen/HPCH composite sponge and much better than the pure collagen sponge. The HPCH sponge also displayed good biodegradability and compatibility. The BPV-loaded 2.4%-HPCH (3.6 wt%) sponge showed the most sustained release profile, and the maximal duration of in vitro release was about 8 times longer than that of the control group BPV-loaded 0.8 %-collagen (0.6 wt%) sponge based on commercial Xaracoll. More importantly, the effective duration of blockade (analgesia) of 21.67 h for the BPV-loaded 2.4 %-HPCH (3.6 wt%) sponge was much longer than that of the bupivacaine hydrochloride solution injection (1 h, 0.8 %-BPV solution) in the guinea pig pin-prick test. Hematoxylin-eosin staining data indicated that a very limited mild inflammatory response was observed at the location where the BPV-loaded HPCH (3.6 wt%) sponge was placed. Thus, the HPCH sponge is expected to serve as a promising drug carrier for the sustained release of bupivacaine in postoperative pain management.

Cell-Regulated Hollow Sulfur Nanospheres with Porous Shell: A Dual-Responsive Carrier for Sustained Drug Release

Cell-Regulated Hollow Sulfur Nanospheres with Porous Shell: A Dual-Responsive Carrier for Sustained Drug Release

β-Cyclodextrin-Based Ultrahigh Stretchable, Flexible, Electro- and Pressure-Responsive, Adhesive, Transparent Hydrogel as Motion Sensor.

In the present work, a multiple-stimuli-responsive hydrogel has been synthesized via polymerization of acrylamide (AAm) and N-hydroxy methyl acrylamide (HMAm) on β-cyclodextrin (β-CD). The synthesized hydrogel β-CD-g-(pAAm/pHMAm) exhibited various striking features like ultrahigh stretchability (>6000%), flexibility, stab resistivity, self-recoverability, electroresponsiveness, pressure-responsiveness, adhesiveness, and high transparency (>90%). Besides, the hydrogel has demonstrated enhanced biocompatibility, UV resistance, and thermoresponsive shape memory behaviors. On the basis of these attractive characteristics of the hydrogel, a flexible pressure sensor for the real-time monitoring of human motion with superior biocompatibility and transparency was fabricated. Moreover, due to the nanofibrillar surface morphology of the β-CD-g-(pAAm/pHMAm) hydrogel, the sensor based on the gel exhibited high sensitivity (0.053 kPa-1 for 0-3.3 kPa). The flexible sensor demonstrates very fast response time (130 ms-210 ms) with adequate stability (5000 cycles). Interestingly, the sensor can rapidly sense both robust (index finger and wrist) motions as well as tiny (swallowing and phonation) physiological actions. In addition, this adhesive hydrogel patch also acts as a potential carrier for the sustained topical release of (∼80.8% in 48 h) the antibiotic drug gentamicin sulfate.

PH-Responsive Eco-Friendly Chitosan–Chlorella Hydrogel Beads for Water Retention and Controlled Release of Humic Acid

For improving the mechanical strength of controlled release fertilizer (CRF) hydrogels, a novel material of Chlorella was employed as a bio-based filler to prepare chitosan–chlorella hydrogel beads with physical crosslink method. Here, the synthesis mechanism was investigated, and the chitosan–chlorella hydrogel beads exhibited enhanced mechanical stability under centrifugation and sonication than pure chitosan hydrogel beads. Chlorella brought more abundant functional groups to original chitosan hydrogel, hence, chitosan–chlorella hydrogel beads represented greater sensitivity and controllable response to external factors including pH, salt solution, temperature. In distilled water, the hydrogel beads with 40 wt% Chlorella reached the largest water absorption ratio of 42.92 g/g. Moreover, the mechanism and kinetics process of swelling behavior of the chitosan–chlorella hydrogel beads were evaluated, and the loading and releasing of humic acid by the hydrogel beads as a carrier material were pH-dependent and adjustable, which exhibit the potential of chitosan–chlorella hydrogel beads in the field of controlled release carrier biomaterials.