Strategy For Sustained Release Research Articles

Sustainable biologically self-healing concrete by smart natural nanotube-hydrogel system

Biologically self-healing concretes are generally composed of immobilized or encapsulated bacterial spores and nutrients. The efficiency of this self-healing approach depends on the effective protection and storage by the carriers. This report describes a novel sustained-release strategy for the improved self-healing function and microcapsule resistance to the cement environment. Halloysite clay nanotubes (HNTs) loaded with the common microbiological nutrient, yeast extract (YE) were encapsulated in calcium alginate microcapsules alongside Bacillus pseudofirmus spores. The encapsulation of the YE-loaded HNTs improved the resistance of the microcapsules to the cement environment, improved the microcapsule-cement interface, while successfully retaining the nutrients after direct contact with the cement pore solution. The self-healing system effectively healed artificial concrete cracks compared to control samples, reducing the crack water tightness by over 95%, and improved the flexural strength regain by approximately 75% after 56 days of wet-dry incubation. The sustained-release mechanism considerably improved the self-healing performance.

Review on Growth Factor Loaded Scaffolds for Rapid Healing of Bone Tissue

Artificial bone implants from various sources, including metals, polymers, and bio-ceramics, turned out to be extensivelyoccupied in present-day tissue engineering applications. The biomaterials provide an essential platform for the osteoblast cells tomultiply, increase, and differentiate into mature osteocytes leading to bone regeneration in the defect site. Apart from biomaterialsand cells, the other essential component in tissue engineering is growth factors. Growth factors are the biomolecules responsiblefor transformation, growth, migration, and cell crawling on the biomaterial's surface. Many growth factors like BMP (BoneMorphogenetic Protein) family, (Transforming Growth Factor Beta) TGF-β, and VEGF (Vascular Endothelial Growth Factor)exhibit a crucial role in angiogenesis, extracellular matrix (ECM) formation and transformation of fibroblasts and other stem cellsinto osteocytes aiding in bone growth. In addition, the growth factors have higher renal clearance making it tough to maintain theirlevels at the site of injury, which demands a sustained release approach. Our review aims to explore various growth factors usedin treating bone defects; the primary objective is to understand each growth factor's role in the healing process and tailor thescaffold according to the requirement. Further, in this review, we have focused on the growth factors being used, their importance,and the sustained release strategies being followed for the efficient distribution of growth factors and, thus, bone healing bycovering the use of different growth factors in conjunction with biomaterials involved in the treatment of bone tissue defects.

Cell-Free Osteoarthritis Treatment with Sustained-Release of Chondrocyte-Targeting Exosomes from Umbilical Cord-Derived Mesenchymal Stem Cells to Rejuvenate Aging Chondrocytes.

As chondrocytes from osteoarthritic cartilage usually exhibit aging and senescent characteristics, targeting aging chondrocytes could be a potential therapeutic strategy. In this study, exosomes derived from umbilical cord-derived mesenchymal stem cells (UCMSC-EXOs) combined with the chondrocyte-targeting capacity and controlled-release system were proposed for osteoarthritis (OA) treatment via rejuvenating aging chondrocytes. The essential functional miRNAs within UCMSC-EXOs were investigated, with the p53 signaling pathway identified as the key factor. To improve the therapeutic efficiency and retention time of UCMSC-EXOs in vivo, the exosomes (EXOs) were engineered on membranes with a designed chondrocyte-targeting polymers, and encapsulated within thiolated hyaluronic acid microgels to form a "two-phase" releasing system, which synergistically facilitated the repair of OA cartilage in a rat model. Together, this study highlighted the rejuvenating effects of UCMSC-EXOs on OA chondrocytes and the potential to combine with chondrocyte-targeting and sustained-release strategies toward a future cell-free OA treatment.

Carbene-Catalyzed Access to Thiochromene Derivatives: Control of Reaction Pathways via Slow Release of Thiols from Disulfides.

Substrates containing disulfide bonds, which are more stable and less smelling, could be used as thiophenol precursors in organic synthesis. Herein, an N-heterocyclic carbene (NHC)-catalyzed reaction between α-bromoenals and 2,2'-dithiodibenzaldehydes was developed. Through the sustained release strategy, the side reaction can be effectively inhibited, and the chiral thiochromene derivatives can be obtained with good yields and high optical purities. Application studies showed encouraging results when the desired products were explored for antimicrobial utilities in pesticide development.

Zwitterionic liquid hydrogel sustained-release strategy for high-performance nanofiltration membrane

Controlling the diffusion of amine monomers plays a crucial role in fabricating well-defined architecture and high-performance nanofiltration (NF) membranes through interfacial polymerization (IP). Herein, a sustained-release strategy was proposed to regulate the interfacial polymerization through a zwitterionic liquid hydrogel transition layer. The hydrogel (Gel) was fabricated via in-situ one-step UV photo-initiated free-radical polymerization between 1-vinyl-3-ethylimidazolium chloride ([VEIm][Cl]) and 3-sulfopropyl methacrylate potassium salt (SMP) on the polyethersulfone (PES) substrate. The polyamide (PA) layer was then formed on the Gel layer by mitigating the diffusion of amine monomers. Low-field time-domain nuclear magnetic resonance (TD NMR) analysis demonstrated that the Gel layer significantly enhanced the water-absorbing capacity of the composite membrane. Positron annihilation lifetime spectroscopy (PALS) also confirmed the Gel-PA composite membrane possessed enlarged free volumes. The obtained Gel-PA composite membrane displayed a permeance of 13.22 L m−2 h−1 bar−1, a high Na2SO4 rejection of 98.23 %, a favorable NaCl/Na2SO4 selectivity of 49.75, outstanding long-term operational stability, and membrane antifouling properties. This sustained-release strategy provides a facile and feasible approach to controlling the IP process and obtaining high-performance nanofiltration membranes.

Targeted stabilization of solid electrolyte interphase and cathode electrolyte interphase in high-voltage lithium-metal batteries by an asymmetric sustained-release strategy

High-voltage lithium (Li)-metal batteries with cell-level energy density over 350 Wh kg−1 are promising energy storage systems. However, the aggressive interphase chemistries associated with highly reactive Li-metal anode and high-voltage cathodes impede their practical applications. Herein, we demonstrate the targeted stabilization of solid electrolyte interphase (SEI) and cathode electrolyte interphase (CEI) in high-voltage Li-metal batteries by asymmetrically sustained-releasing different additives. An asymmetric sustained-release film loaded with lithium bis-(oxalate)borate (LiBOB) and LiNO3 on each side is investigated as a proof-of-concept. The sustained-releasing of LiBOB and LiNO3 can maintain a localized concentration at the high-voltage cathode and Li-metal anode fronts respectively, thus forming a stable B-containing CEI and N-containing SEI. As such, issues like dendrites growth, parasitic side reactions and transition metals dissolution under high-voltage are addressed simultaneously. Based on this strategy, the 30 μm Li|LiNi0.5Co0.2Mn0.3O2 (4.1 mAh cm−2) batteries deliver a capacity retention of 80% after 173 cycles under a cut-off voltage of 4.5 V.

Progress and Challenges of Anti-VEGF Agents and Their Sustained-Release Strategies for Retinal Angiogenesis.

Currently, the treatment for ocular neovascular diseases, including diabetic macular edema (DME) and age-related macular degeneration (AMD), mainly involves repeated intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. Although it can preserve vision, repeated injections are an invasive treatment modality, leading to serious complications and reducing patient adherence to treatment. To reduce the frequency of administration, prolong the time of drug action, and avoid repeated intravitreal injections, the combination of sustained-release materials with anti-VEGF drug therapy has become an emphasis in ophthalmology. In this review, we highlight the current state of anti-VEGF technology, its challenges, and the sustained-release strategies under investigation or being used in clinical practice. Both continuous release and considerable therapeutic effects can be achieved by encapsulating anti-VEGF drugs in sustained-release materials to minimize the number of intravitreal injections. At present, two sustained-release materials are being tested in clinical research, and although basic research shows the strong therapeutic application prospects of extended-release drugs, its challenges mainly involve the discrepancy between the release rates in vitro and the efficiency of the drugs in vivo. Briefly, sustained release of anti-VEGF agents is an advantageous strategy for treating retinal angiogenesis.

Hydrogel microcapsules containing engineered bacteria for sustained production and release of protein drugs

Subcutaneous administration of sustained-release formulations is a common strategy for protein drugs, which avoids first pass effect and has high bioavailability. However, conventional sustained-release strategies can only load a limited amount of drug, leading to insufficient durability. Herein, we developed microcapsules based on engineered bacteria for sustained release of protein drugs. Engineered bacteria were carried in microcapsules for subcutaneous administration, with a production-lysis circuit for sustained protein production and release. Administrated in diabetic rats, engineered bacteria microcapsules was observed to smoothly release Exendin-4 for 2 weeks and reduce blood glucose. In another example, by releasing subunit vaccines with bacterial microcomponents as vehicles, engineered bacterial microcapsules activated specific immunity in mice and achieved tumor prevention. The engineered bacteria microcapsules have potential to durably release protein drugs and show versatility on the size of drugs. It might be a promising design strategy for long-acting in situ drug factory.

Sustained transdermal delivery of human growth hormone from niosomal gel: in vitro and in vivo studies

Human growth hormone (hGH) is widely used to treat several diseases for decades. However, the current treatment regime requires frequent injections via subcutaneous route due to short in vivo half-life, which leads to pain and poor patient compliance. In this study, a novel transdermal (non-invasive) hGH loaded niosomes gel was prepared to reduce the frequency of subcutaneous injections and to improve the patient compliance. Niosomes were prepared by film hydration technique at three levels of cholesterol. The particle size and entrapment efficiency increases with an increase in the level of cholesterol. Transmission electron microscopy images confirmed the spherical shape of niosomes without aggregation. Texture profiles analysis indicates that the niosomal gel has the required mechanical properties for transdermal application. The ex vivo permeation profile showed sustain hGH release for 4 days from the niosomal gel compared to 24 h from the control gel without niosomes. A rabbit skin irritation study showed no sign of irritation after application of niosomal gel. The pharmacokinetic parameters in the rat model showed 7.22-fold higher bioavailability with niosomal gel compared to control gel. In conclusion, the study demonstrated the potential of niosomal gel as an effective long-term sustained release strategy for hGH delivery to replace traditional subcutaneous injections.

Targeted Stabilization of Solid Electrolyte Interphase and Cathode Electrolyte Interphase in High-Voltage Lithium-Metal Batteries by an Asymmetric Sustained-Release Strategy

Targeted Stabilization of Solid Electrolyte Interphase and Cathode Electrolyte Interphase in High-Voltage Lithium-Metal Batteries by an Asymmetric Sustained-Release Strategy

Construction of hierarchical nanocarrier via a “MOFs plus graphene” strategy for sustained release and rust-induced self-healing

The fact that conventional self-healing coating is susceptible to the leakage of self-healing agents and investigated so far to mostly cope with the corrosion resulted from the mechanical damage of coating as a function of complex internal/external stimuli motivates researchers to fucus on the application of innovative materials on the coating system. Herein, a gallic acid-loaded hierarchical nanocarrier (UiO-66-NH2@rGO) combined porous UiO-66-NH2 (Zr6O4(OH)4(bdc-NH2)6; bdc-NH2 = 2-amino-1,4-benzenedicarboxylate) (UiO-Universitetet i Oslo) frameworks with reduce graphene oxide (rGO), and was engineered to assist the self-healing at defined target sites beneath the lossless coating. With the prominent stability, abundant encapsulation and straightforward sustained release, this hierarchical structure contributes to preventing leakage of guests suffered from the structure damage and simplify the response factor of self-healing effect. Besides, the self-healing on mild steel is induced by the formation of rust layer and firstly introduced for the inhibition of local coating delamination and corrosion activity – that is, an additional metal-phenolic passivating film deposited via the continuous etching and assembly with Fe (III) from rust layers. This work contributes to the focus of researchers on the frameworks or hierarchical material in the field of self-healing material and molecule delivery while also providing a novel strategy of target healing to the long-term corrosion inhibition of lossless coating.

Mitigation of vacancy with ammonium salt-trapped ZIF-8 capsules for stable perovskite solar cells through simultaneous compensation and loss inhibition.

Due to the easy loss of ions during synthesis or usage, vacancies in perovskite film are ubiquitous, accelerating the degradation of perovskite materials and seriously hampering the stability of perovskite solar cells (PSCs). Herein, to simultaneously compensate for vacancies and reduce ammonium cation loss, a sustained release strategy was proposed by introducing multi-functional capsules consisting of zeolitic imidazolate framework-8 (ZIF-8) encapsulation agent and ammonium iodide salts as interlayer between the perovskite and hole transport layer. In the capsule interlayer, not only are ammonium iodide salts in ZIF-8 pores released to the perovskite layer, compensating for the vacancies, but the ZIF-8 also prevents the organic component of perovskite from evaporating and isolates the perovskite from moisture. As a consequence, decreased trap density, improved device efficiency, and enhanced stability of PSCs are obtained owing to the successful passivation of defects by the introduced capsules. ZIF-8@FAI shows the highest efficiency of 19.13% and a stabilized PCE over 93% of the initial efficiency at maximum power point for 150 h. This work provides a new strategy to improve efficiency and stability of PSCs based on the large family of porous materials.

Structural characterization and developability assessment of sustained release hydrogels for rapid implementation during preclinical studies

Sustained-release formulations are important tools to convert efficacious molecules into therapeutic products. Hydrogels enable the rapid assessment of sustained-release strategies, which are important during preclinical development where drug quantities are limited and fast turnaround times are the norm. Most research in hydrogel-based drug delivery has focused around synthesizing new materials and polymers, with limited focus on structural characterization, technology developability and implementation. Two commercially available thermosensitive hydrogel systems, comprised of block copolymers of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PLGA) and poly(lactide-co-caprolactone)-b-poly(ethyleneglycol)-b-poly(lactide-co-caprolactone) (PLCL), were evaluated during this study. The two block copolymers described in the study were successfully formulated to form hydrogels which delayed the release of lysozyme (> 20 days) in vitro. Characterization of formulation attributes of the hydrogels like Tsol-gel temperature, complex viscosity and injection force showed that these systems are amenable to rapid implementation in preclinical studies. Understanding the structure of the gel network is critical to determine the factors controlling the release of therapeutics out of these gels. The structures were characterized via the gel mesh sizes, which were estimated using two orthogonal techniques: small angle X-ray scattering (SAXS) and rheology. The mesh sizes of these hydrogels were larger than the hydrodynamic radius (size) of lysozyme (drug), indicating that release through these gels is expected to be diffusive at all time scales rather than sub-diffusive. In vitro drug release experiments confirm that diffusion is the dominating mechanism for lysozyme release; with no contribution from degradation, erosion, relaxation, swelling of the polymer network or drug-polymer interactions. PLGA hydrogel was found to have a much higher complex viscosity than PLCL hydrogel, which correlates with the slower diffusivity and release of lysozyme seen from the PLGA hydrogel as compared to PLCL hydrogel. This is due to the increased frictional drag experienced by the lysozyme molecule in the PLGA hydrogel network, as described by the hydrodynamic theory.

Immunizing lithium metal anodes against dendrite growth using protein molecules to achieve high energy batteries

The practical applications of lithium metal anodes in high-energy-density lithium metal batteries have been hindered by their formation and growth of lithium dendrites. Herein, we discover that certain protein could efficiently prevent and eliminate the growth of wispy lithium dendrites, leading to long cycle life and high Coulombic efficiency of lithium metal anodes. We contend that the protein molecules function as a “self-defense” agent, mitigating the formation of lithium embryos, thus mimicking natural, pathological immunization mechanisms. When added into the electrolyte, protein molecules are automatically adsorbed on the surface of lithium metal anodes, particularly on the tips of lithium buds, through spatial conformation and secondary structure transformation from α-helix to β-sheets. This effectively changes the electric field distribution around the tips of lithium buds and results in homogeneous plating and stripping of lithium metal anodes. Furthermore, we develop a slow sustained-release strategy to overcome the limited dispersibility of protein in the ether-based electrolyte and achieve a remarkably enhanced cycling performance of more than 2000 cycles for lithium metal batteries.

Sustained and targeted episcleral delivery of celecoxib in a rabbit model of retinal and choroidal neovascularization

BackgroundTo evaluate the efficacy of selective episcleral delivery of celecoxib formulated in a sustained-release episcleral exoplant on a model of retinal and choroidal neovascularization induced in rabbits by subretinal injection of matrigel combined with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF).MethodsNine New Zealand white rabbits were randomly assigned to three groups (episcleral celecoxib exoplant, intravitreal bevacizumab injection and control group). The bFGF was mixed with matrigel at a concentration of 10 ug/0.1 mL, and VEGF was mixed with matrigel at a concentration of 2 ug/0.1 mL. Animals assigned to celecoxib or intravitreal bevacizumab groups were treated within 03 days from matrigel injection. Fluorescein angiography (FA) and electroretinography (ERG) were performed 5 days, 2, 4 and 8 weeks after matrigel injection. Persistence or regression of three clinical features (subretinal hyperfluorescence, retinal vascular tortuosity and retinal fibrotic spots) was independently evaluated in each study group at all follow-up periods. Statistical analysis using Fisher’s exact test was performed to compare the frequency of findings at each time point between treated groups and control.ResultsIn all study eyes, matrigel induced the appearance of subretinal blebs and the development of retinal and subretinal neovascularization characterized by progressive and late hyperfluorescence on FA. Persistence of subretinal hyperfluorescence was higher in non-treated (control) animals compared to celecoxib (p = 0.0238) treated animals. The mean b-wave amplitude ratios of ERG recordings did not reveal statistically significant differences between the study groups. Control animals retained in average 40% (± 7%) of the pre-treatment recorded b-wave amplitude, compared to 53% (± 29%) after bevacizumab and 53% (± 17%) after celecoxib treatment.ConclusionIn this rabbit model of retinal and subretinal neovascularization, episcleral celecoxib delivery was demonstrated to significantly inhibit neovascularization. It was also noticed, although not statistically significant, an apparent effect of episcleral celecoxib on preventing tractional retinal detachment secondary to epiretinal fibrovascular proliferation. The transscleral delivery of celecoxib combined with sustained-release strategy may have impact in the treatment of retinal and choroidal proliferative diseases.

Pulmonary liposomal formulations encapsulated procaterol hydrochloride by a remote loading method achieve sustained release and extended pharmacological effects

Drug inhalation provides localized drug therapy for respiratory diseases. However, the therapeutic efficacy of inhaled drugs is limited by rapid clearance from the lungs. Small hydrophilic compounds have short half-lives to systemic absorption. We developed a liposomal formulation as a sustained-release strategy for pulmonary delivery of procaterol hydrochloride (PRO), a short-acting pulmonary β2-agonist for asthma treatment. After PRO-loaded liposomes were prepared using a pH gradient (remote loading) method, 100-nm liposomes improved residence times of PRO in the lungs. PRO encapsulation efficiency and release profiles were examined by screening several liposomal formulations of lipid, cholesterol, and inner phase. Although PRO loading was not achieved using the conventional hydration method, PRO encapsulation efficiency was >60% using the pH gradient method. PRO release from liposomes was sustained for several hours depending on liposomal composition. The liposomal formulation effects on the PRO behavior in rat lungs were evaluated following pulmonary administration in vivo. Sustained PRO release was achieved using simplified egg phosphatidylcholine (EPC)/cholesterol (8/1) liposome in vitro, and greater PRO remnants were observed in rat lungs following pulmonary administration. Extended pharmacological PRO effects were observed for 120min in a histamine-induced bronchoconstriction guinea pig model. We indicated the simplified EPC/cholesterol liposome potential as a controlled-release PRO carrier for pulmonary administration.

The contribution of plasmid design and release to in vivo gene expression following delivery from cationic polymer modified scaffolds

Tissue engineering scaffolds capable of gene delivery can provide a structure that supports tissue formation while also inducing the expression of inductive factors. Sustained release strategies are hypothesized to maintain elevated plasmid concentrations locally that can enhance gene transfer. In this report, we investigate the relationship between plasmid release kinetics and the extent and duration of transgene expression. Scaffolds were fabricated from polymer microspheres modified with cationic polymers (polyethylenimine, poly( l-lysine), poly(allylamine hydrochloride), polydiallyldimethylammonium) or polydopamine (PD), with PD enhancing incorporation and slowing release. In vivo implantation of scaffolds into the peritoneal fat pad had no significant changes in the level and duration of transgene expression between PD and unmodified scaffolds. Control studies with plasmid dried onto scaffolds, which exhibited a rapid release, and scaffolds with extended leaching to reduce initial quantities released had similar levels and duration of expression. Changing the plasmid design, from a cytomegalovirus (CMV) to an ubiquitin C (UbC) promoter substantially altered the duration of expression. These studies suggest that the initial dose released and vector design affect the extent and duration of transgene expression, which may be sustained over several weeks, potentially leading to numerous applications in cell transplantation and regenerative medicine.