Tunable Release Research Articles

Research on the preparation of antimicrobial material based on thermoplastic polyurethane and drug release control.

It's crucial of antimicrobial properties in materials is growing as people desire to live healthier. The purpose of this work was to use thermoplastic polyurethane (TPU) as a matrix to produce an antimicrobial material with a tunable drug release rate. Filaments with a diameter of 1.75 ± 0.08mm were prepared by hot-melt processing technology utilizing TPU, the modifier polyethylene oxide (PEO) and ciprofloxacin hydrochloride monohydrate (CPFX) as raw materials. The corresponding models were then printed using fused deposition type (FDM) 3D printing for performance testing. Results demonstrate the uniform fiber morphology and strong mechanical properties of the four samples, each of which was composed of a different ratio of components. The addition of PEO caused a change to the drug release mechanism, increased the material hydrophilicity, and generated extra pores during the dissolution process. This composite exhibited sustained antimicrobial activity even after 21days of rotary immersion, as shown by in vitro dissolution and zone inhibition tests.

Sydnthiones are versatile bioorthogonal hydrogen sulfide donors

Hydrogen sulfide (H2S) is an important endogenous gasotransmitter, but the bioorthogonal reaction triggered H2S donors are still rare. Here we show one type of bioorthogonal H2S donors, sydnthiones (1,2,3-oxadiazol-3-ium-5-thiolate derivatives), which was designed with the aid of density functional theory (DFT) calculations. The reactions between sydnthiones and strained alkynes provide a platform for controllable, tunable and mitochondria-targeted release of H2S. We investigate the reactivity of sydnthiones‒dibenzoazacyclooctyne (DIBAC) reactions and their orthogonality with two other bioorthogonal cycloaddition pairs: tetrazine‒norbornene (Nor) and tetrazine‒monohydroxylated cyclooctyne (MOHO). By taking advantage of these mutually orthogonal reactions, we can realize selective labeling or drug release. Furthermore, we explore the role of H2S, which is released from the sydnthione-DIBAC reaction, on doxorubicin-induced cytotoxicity. The results demonstrate that the viability of H9c2 cells can be significantly improved by pretreating with sydnthione 1b and DIBAC for 6 h prior to exposure to Dox.

Phase-separating peptide coacervates with programmable material properties for universal intracellular delivery of macromolecules

Phase-separating peptides (PSPs) self-assembling into coacervate microdroplets (CMs) are a promising class of intracellular delivery vehicles that can release macromolecular modalities deployed in a wide range of therapeutic treatments. However, the molecular grammar governing intracellular uptake and release kinetics of CMs remains elusive. Here, we systematically manipulate the sequence of PSPs to unravel the relationships between their molecular structure, the physical properties of the resulting CMs, and their delivery efficacy. We show that a few amino acid alterations are sufficient to modulate the viscoelastic properties of CMs towards either a gel-like or a liquid-like state as well as their binding interaction with cellular membranes, collectively enabling to tune the kinetics of intracellular cargo release. We also demonstrate that the optimized PSPs CMs display excellent transfection efficiency in hard-to-transfect cells such as primary fibroblasts and immune cells. Our findings provide molecular guidelines to precisely program the material properties of PSP CMs and achieve tunable cellular uptake and release kinetics depending on the cargo modality, with broad implications for therapeutic applications such as protein, gene, and immune cell therapies.

Kinetic and Mechanistic Release Studies on Hyaluronan Hydrogels for Their Potential Use as a pH-Responsive Drug Delivery Device.

Hyaluronic acid, a biocompatible polymer, holds significant potential for drug delivery applications. Its variable degree of protonation, which entails tunable physical properties, makes it an ideal candidate for developing pH-sensitive hydrogels. Like other smart drug delivery systems, pH-responsive hydrogels can enhance medical treatment and expedite the healing process. However, the inherent complexity of hydrogels poses challenges in identifying suitable matrix systems. This study evaluates the potential of thiolated hyaluronic acid hydrogels, physically cross-linked with deacetylated disaccharide units of the polymer, for use in drug delivery. Using low-molecular-weight dextrans as model drugs, we investigated the system's response to different pH environments in terms of swelling as well as the kinetic and mechanistic release of the encapsulated compound. The data suggest tunable release properties of the gel regarding drug size and pH value. Our results demonstrate the gel system's potential for smart drug delivery. We anticipate that this system is a promising candidate for use in transdermal wound healing applications and strongly encourage further investigations using other sorts of (model) drugs to gain a more detailed insight into its pH-responsive transport qualities.

Development of a Starch‐Based Foam System With Oxygen‐Controlled Release

AbstractCalcium peroxide (CP) offers promising applications in the food industry due to its oxygen‐donating properties. However, the rapid release of oxygen by CP needs to be addressed for fruit preservation applications. In this paper, a starch‐based foam is prepared to embed CP to alleviate this problem. Results show that the starch foam extruded at 150 °C and 150 rpm shows a high foaming ratio of 19.28 and displays a high moisture adsorption capacity of 0.21 g water/g solids when stored at 97% relative humidity (RH), which effectively regulates the water accessibility to CP. The initial oxygen release rate of the embedded CP is reduced from 0.19 to 0.07 mmol L−1 h−1, and the release time is prolonged. The wet‐stored foam shows excellent cushioning ability, with a recovery ratio higher than 72%. The starch‐based active foam with a tunable release of oxygen and cushioning properties can be used as active packaging for fresh fruit transportation and preservation.

Synergistic effects of graphene nanoparticles on the thermomechanical properties of PEEK-HNTs nanocomposites

In our previous study, we selected a 3% concentration (PH3) from various prepared PEEK-HNTs nanocomposites. Poly (ether ether ketone) (PEEK) is characterized by non-perfluorinated aromatic compounds with 1,4-disubstituted phenyl groups linked by carbonyl (––CO––) and ether (––O––) groups, offering exceptional thermal stability, mechanical strength, tribological properties, and chemical resistance at high temperatures. Halloysite nanotubes (HNTs) are known for their non-toxic, environmentally friendly, cost-effective properties, with tunable release and rapid adsorption rates. In this study, we prepared graphene nanoparticle (GNP) composites at three different concentrations while maintaining constant PH3 levels. The composites underwent comprehensive characterization using FTIR, TGA, DSC, SEM, and DMA techniques. Thermomechanical properties were evaluated using a universal testing machine. Results demonstrate significant enhancements in hardness, impact strength, elongation at break, tensile modulus, and flexural modulus, with the highest performance observed in the GNP-loaded 0.3% (PHG3) concentration. The synergistic effects of GNP fillers in PH3 are attributed to enhanced interfacial adhesion and favorable interactions with the polymer matrix.

Ethoxy Acetalated Dextran-Based Biomaterials for Therapeutic Applications.

A novel class of pH-responsive polymers, acetalated dextran, has emerged in the field of biomaterials. These versatile materials are derived from dextran through a simple acetalation reaction, allowing for the creation of polymers with a tunable release profile which allows the controlled release of encapsulated therapeutics in response to acidic environments. Despite their recent introduction, acetalated dextran has rapidly garnered significant interest due to its potential for various therapeutic applications. This review delves specifically into the recent advancements of ethoxy acetalated dextran or Ace-DEX, a particular acetalated dextran with a distinct advantage: its degradation products (acetone and ethanol) are less toxic compared to other variants that produce methanol. The focus of this review is the diverse range of biomedical applications currently being explored for Ace-DEX-based scaffolds. Finally, this review concludes by addressing the existing challenges associated with Ace-DEX and outlining potential future research directions within this promising field.

A Spironolactone-Based Prototype of an Innovative Biomedical Patch for Wound Dressing Applications.

The electrospinning process is an effective technique for creating micro- and nanofibers from synthetic and natural polymers, with significant potential for biomedical applications and drug delivery systems due to their high drug-loading capacity, large surface area, and tunable release times. Poly(L-lactic acid) (PLLA) stands out for its excellent thermo-mechanical properties, biodegradability, and bioabsorbability. Electrospun PLLA nanofibrous structures have been extensively investigated as wound dressings, sutures, drug delivery carriers, and tissue engineering scaffolds. This study aims to create and characterize electrospun PLLA membranes loaded with spironolactone (SP), mimicking active compounds of Ganoderma lucidum (GL), to develop a biodegradable patch for topical wound-healing applications. GL, a medicinal mushroom, enhances dermal wound healing with its bioactive compounds, such as polysaccharides and ganoderic acids. Focusing on GL extracts-obtained through green extraction methods-and innovative drug delivery, we created new fibers for wound-healing potential applications. To integrate complex mixtures of bioactive compounds into the fibers, we developed a prototype using a single pure substance representing the extract mixture. This painstaking work presents the results of the fabricating, wetting, moisture properties, material resilience, and full characterization of the product, providing a robust rationale for the fabrication of fibers imbued with more complex extracts.

Chemoselective Reagents for the Traceless Bioreversible Modification of Native Proteins.

Nature utilizes bioreversible post-translational modifications (PTMs) to spatiotemporally diversify protein function. Mimicking Nature's approach, chemists have developed a variety of chemoselective regents for traceless, bioreversible modification of native proteins. These strategies have found utility in the development of reversible covalent inhibitors and degraders as well as the synthesis of functional protein conjugates for delivery into cells. This Viewpoint provides a snapshot of such tools, which currently cover Cys, Ser, Thr, Lys, Asp, and Glu residues and the N terminus. Additionally, we explore how bioreversible reagents, originally developed by research communities with differing objectives, can be utilized synergistically. Looking forward, we discuss the need for developing bioreversible reagents for labeling His, Tyr, Arg, Trp, Asn, Gln, and Met residues and the C-terminus as well as the installation of dynamic PTMs. Finally, to broaden the applicability of these tools, we point out the importance of developing modular release scaffolds with tunable release times and responsiveness to multiple endogenous triggers. We anticipate that this Viewpoint will catalyze further research and technological breakthroughs in this rapidly evolving field.

Multiresponsive 4D Printable Hydrogels with Anti-Inflammatory Properties.

Multiresponsive hydrogels are valuable as biomaterials due to their ability to respond to multiple biologically relevant stimuli, i.e., temperature, pH, or reactive oxygen species (ROS), which can be present simultaneously in the body. In this work, we synthesize triple-responsive hydrogels through UV light photopolymerization of selected monomer compositions that encompass thermoresponsive N-isopropylacrylamide (NIPAM), pH-responsive methacrylic acid (MAA), and a tailor-made ROS-responsive diacrylate thioether monomer (EG3SA). As a result, smart P[NIPAMx-co-MAAy-co-(EG3SA)z] hydrogels capable of being manufactured by digital light processing (DLP) 4D printing are obtained. The thermo-, pH-, and ROS-response of the hydrogels are studied by swelling tests and rheological measurements at different temperatures (25 and 37 °C), pHs (3, 5, 7.4, and 11), and in the absence or presence of ROS (H2O2). The hydrogels are employed as matrixes for the encapsulation of ketoprofen (KET), an anti-inflammatory drug that shows a tunable release, depending on the hydrogel composition and stimuli applied. The cytotoxicity properties of the hydrogels are tested in vitro with mouse embryonic fibroblasts (NIH 3T3) and RAW 264.7 murine macrophage (RAW) cells. Finally, the anti-inflammatory properties are assessed, and the results exhibit a ≈70% nitric oxide reduction up to base values of pro-inflammatory RAW cells, which highlights the anti-inflammatory capacity of P[NIPAM80-co-MAA15-co-(EG3SA)5] hydrogels, per se, without being necessary to encapsulate an anti-inflammatory drug within their network. It opens the route for the fabrication of customizable 4D printable scaffolds for the effective treatment of inflammatory pathologies.

Nanogel: A versatile drug delivery system for the treatment of various diseases and their future perspective.

Nanogel (NG) drug delivery systems have emerged as promising tools for targeted and controlled drug release, revolutionizing treatment approaches across various diseases.Their unique physicochemical properties, such as nano size, high surface area,biocompatibility, stability, and tunable drug release, make themideal carriers for a wide range of therapeutic agents. Nanogels (NGs), characterized by their 3D network of crosslinked polymers, offer unique edges like high drug loading capacity, controlled release, and targeted delivery. Additionally, the diverse applications of NGs in medical therapeutics highlight their versatility and potential impact on improving patient outcomes. Their application spans cancer treatment, infectious diseases, and chronic conditions, allowing for precise drug delivery to specific tissues or cells, minimizing side effects, and enhancing therapeutic efficacy. Despite their potential, challenges such as scalability, manufacturing reproducibility, and regulatory hurdles must be addressed. Achieving clinical translation requires overcoming these obstacles to ensure therapeutic payloads' safe and efficient delivery. Strategies such as surface modification and incorporating stimuli-responsive elements enhanced NG performance and addressed specific therapeutic challenges. Advances in nanotechnology, biomaterials, and targeted drug design offer opportunities to improve the performance of NGs and address current limitations. Tailoring NGs for exploring combination therapies and integrating diagnostics for real-time monitoring represent promising avenues for future research. In conclusion, NG drug delivery systems have demonstrated tremendous potential in diverse disease applications. Overcoming challenges and leveraging emerging technologies will pave the way for their widespread clinical implementation, ushering in a new era of precision medicine and improved patient care.

Tuning Mg Doping and Features of Bone-like Apatite Nanoparticles Obtained via Hydrothermal Synthesis.

Nanocrystalline apatites have been intensively studied for decades, not only for their well-known mimesis of bone apatite but also for applicative purposes, whether as biomaterials for skeletal repair or more recently for a variety of nanomedical applications enabled by their peculiar surface characteristics. Particularly, ion-doped apatites are of great interest because the incorporation of foreign ions in the composition of apatite (nano)crystals alters the bulk and surface properties, modifying their ability to interact with the external environment. This is clearly seen in the physiology of bone tissue, whose mineral phase, a low crystallinity apatitic phase, can dynamically exchange ions with cells, thus driving bone metabolism. Taking bone mineral as a model, the present work describes the development of Mg-doped hydroxyapatite nanoparticles, exploiting hydrothermal synthesis to achieve extents of Mg2+ doping hardly achieved before and using citrate to develop stable apatite colloidal dispersions. Morphological and physicochemical analyses, associated with in-depth investigation of ions populating the apatitic lattice and the nonapatitic surface layer, concurred to demonstrate the cooperative presence of Mg2+ and citrate ions, affecting the dynamic ion retention/release mechanisms. Achieving high Mg2+ doping rates and understanding how Mg doping translates into surface activation of apatite-based nanoparticles is expected to foster the design of novel smart and tunable devices, to adsorb and release ionic species and cargo molecules, with potential innovations in the biomedical field or even beyond, as in catalysis or for environmental remediation.

3D printed O2-generating scaffolds enhance osteoprogenitor- and type H vessel recruitment during bone healing

Oxygen (O2)-delivering tissue substitutes have shown tremendous potential for enhancing tissue regeneration, maturation, and healing. As O2 is both a metabolite and powerful signaling molecule, providing controlled delivery is crucial for optimizing its beneficial effects in the treatment of critical-sized injuries. Here, we report the design and fabrication of 3D-printed, biodegradable, O2-generating bone scaffold comprising calcium peroxide (CPO) that once hydrolytically activated, provides long-term generation of oxygen at a controlled, concentration-dependent manner, and polycaprolactone (PCL), a hydrophobic polymer that regulate the interaction of CPO with water, preventing burst release of O2 at early time points. When anoxic conditions were simulated in vitro, CPO-PCL scaffolds maintained the survival and proliferation of human adipose-derived stem/stromal cells (hASCs) relative to PCL-only controls. We assessed the in vivo osteogenic efficacy of hASC-seeded CPO-PCL scaffolds implanted in a non-healing critical-sized 4-mm calvarial defects in nude mice for 8 weeks. Even without exogenous osteoinductive factors, CPO-PCL scaffolds demonstrated increased new bone volume compared to PCL-only scaffolds as verified by both microcomputed tomography analysis and histological assessments. Lastly, we employed a quantitative 3D lightsheet microscopy platform to determine that O2-generating scaffolds had similar vascular volumes with slightly higher presence of CD31hiEmcnhi pro-osteogenic, type H vessels and increased number of Osterix+ skeletal progenitor cells relative to PCL-only scaffolds. In summary, 3D-printed O2 generating CPO-PCL scaffolds with tunable O2 release rates provide a facile, customizable strategy for effectively treating, craniofacial bone defects. Statement of significanceOxygen(O2)-delivering bone substitutes show promise in defect repair applications by supplying O2 to the cells within or around the graft, improving cell survivability and enhancing bone matrix mineralization. A novel O2-generating bone scaffold has been 3D printed for the first-time which ensures patient and defect specificity. 3D printed calcium peroxide-polycaprolactone (CPO-PCL) bone scaffold provides uninterrupted O2 supply for 22 days allowing cell survival in deprived O2 and nutrient conditions. For the first time, O2-driven bone regenerative environment in mice calvaria has been captured by light-sheet imaging which illuminates abundance of Osterix+ cells, angiogenesis at a single cell resolution indicating active site of bone remodeling and growth in the presence of O2.

Hydroxypropyl methylcellulose phthalate films reinforced with nanocrystalline cassava starch and intended its applications for colonic drug delivery

Controlled-release drug delivery systems are crucial for improving therapeutic efficacy and patient compliance. Hydroxypropyl methylcellulose phthalate (HPMCP) films are promising candidates due to their film-forming properties and tunable release profiles. However, their mechanical properties can limit their applicability. This study aimed to assess the effect of addition of nanocrystalline cassava (NCS) starches to HPMCP films on the physicochemical and mechanical properties and the ability of films to control drug release rate. Reinforced HPMCP films with 2, 4 and 6 % w/w of NCS were characterized as a function of the microstructure, X-ray diffraction pattern, mechanical properties, and dissolution property. It was found that increasing starch amount induced an increase in heterogeneity of the film microstructure and crystallinity. The tensile strength of HPMCP films increased with addition of starches, while the elongation at break decreased. The lowest dissolution in pH 6.8 phosphate buffer solution was found for films containing NCS at 2 and 4 % w/w. For the application purposes, HPMCP containing different amounts of NCS was used to coat over diclofenac sodium tablets. The tablets coated with HPMCP containing 4 % w/w NCS showed the lowest drug release of 73.5 % in pH 6.8 phosphate buffer solution at 240 min. According to our results, the addition of NCS at adequate amount allowed to improve the mechanical properties of HPMCP films and to decrease the drug release rate which is important for the site-specific drug delivery process.

Polyvinyl alcohol-based capsule shells manufactured by injection molding as ready-to-use moisture barriers for the development of delivery systems

In this work, feasibility of injection molding was demonstrated for manufacturing capsule shells. 600 µm-thick prototypes were successfully molded with pharmaceutical-grade low-viscosity polyvinyl alcohols (PVAs), possibly added with a range of different fillers. They showed reproducible weight and thickness (CV < 2 and 5, respectively), compliant behavior upon piercing (holes diameter analogous to the reference), tunable release performance (immediate and pulsatile), and moisture protection capability. To assess the latter, an on-line method relying on near infrared spectroscopy measurements was set-up and validated. Based on the data collected and considering the versatility IM would provide for product shape/thickness/composition, PVA-based molded shells could help widening the portfolio of ready-to-use capsules, representing an interesting alternative to those commercially available. Indeed, these capsules could be filled with various formulations, even those with stability issues, and intended either for oral administration or for pulmonary delivery via single-dose dry powder inhalers.

Injectable hydrogel based on liposome self-assembly for controlled release of small hydrophilic molecules

Controlled release of low molecular weight hydrophilic drugs, administered locally, allows maintenance of high concentrations at the target site, reduces systemic side effects, and improves patient compliance. Injectable hydrogels are commonly used as a vehicle. However, slow release of low molecular weight hydrophilic drugs is very difficult to achieve, mainly due to a rapid diffusion of the drug out of the drug delivery system. Here we present an injectable and self-healing hydrogel based entirely on the self-assembly of liposomes. Gelation of liposomes, without damaging their structural integrity, was induced by modifying the cholesterol content and surface charge. The small hydrophilic molecule, sodium fluorescein, was loaded either within the extra-liposomal space or encapsulated into the aqueous cores of the liposomes. This encapsulation strategy enabled the achievement of controlled and adjustable release profiles, dependent on the mechanical strength of the gel. The hydrogel had a high mechanical strength, minimal swelling, and slow degradation. The liposome-based hydrogel had prolonged mechanical stability in vivo with benign tissue reaction. This work presents a new class of injectable hydrogel that holds promise as a versatile drug delivery system. Statement of significanceThe porous nature of hydrogels poses a challenge for delivering small hydrophilic drug, often resulting in initial burst release and shorten duration of release. This issue is particularly pronounced with physically crosslinked hydrogels, since their matrix can swell and dissipate rapidly, but even in cases where the polymers in the hydrogel are covalently cross-linked, small molecules can be rapidly released through its porous mesh. Here we present an injectable self-healing hydrogel based entirely on the self-assembly of liposomes. Small hydrophilic molecules were entrapped inside the extra-liposomal space or loaded into the aqueous cores of the liposomes, allowing controlled and tunable release profiles.

Smart responsive in situ hydrogel systems applied in bone tissue engineering.

The repair of irregular bone tissue suffers severe clinical problems due to the scarcity of an appropriate therapeutic carrier that can match dynamic and complex bone damage. Fortunately, stimuli-responsive in situ hydrogel systems that are triggered by a special microenvironment could be an ideal method of regenerating bone tissue because of the injectability, in situ gelatin, and spatiotemporally tunable drug release. Herein, we introduce the two main stimulus-response approaches, exogenous and endogenous, to forming in situ hydrogels in bone tissue engineering. First, we summarize specific and distinct responses to an extensive range of external stimuli (e.g., ultraviolet, near-infrared, ultrasound, etc.) to form in situ hydrogels created from biocompatible materials modified by various functional groups or hybrid functional nanoparticles. Furthermore, "smart" hydrogels, which respond to endogenous physiological or environmental stimuli (e.g., temperature, pH, enzyme, etc.), can achieve in situ gelation by one injection in vivo without additional intervention. Moreover, the mild chemistry response-mediated in situ hydrogel systems also offer fascinating prospects in bone tissue engineering, such as a Diels-Alder, Michael addition, thiol-Michael addition, and Schiff reactions, etc. The recent developments and challenges of various smart in situ hydrogels and their application to drug administration and bone tissue engineering are discussed in this review. It is anticipated that advanced strategies and innovative ideas of in situ hydrogels will be exploited in the clinical field and increase the quality of life for patients with bone damage.

Engineering Long‐Releasing Hollow‐like or Condensed Progesterone Hormone Microcrystals with Controlled Polymorphism

Progesterone is an endogenous steroid hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. Progesterone crystallization techniques have previously reported. Among these techniques, solvent crystallization and different solvent:anti‐solvent systems are considered. Herein, the selective development of either hollow‐like or condensed progesterone microcrystals in elevated yield with controlled polymorphism, habit, and release is described for the first time. For the hollow microcrystals, isopropyl alcohol (IPA) and double‐deionized water (DDW) system is developed as solvent:anti‐solvent, while acetonitrile (AcN) and DDW system are developed for the condensed microcrystals. The microcrystals obtained from both developed crystallization systems are thoroughly investigated with varied microscopic techniques, including brightfield and scanning electron microscopy (SEM), thermal analysis by differential scanning calorimetry (DSC), and crystallography by powder X‐ray diffraction (PXRD) and single XRD, and have been compared. Results show that the crystals of the IPA:DDW crystallization system are hollow and exhibit several habits, whereas the microcrystals of the AcN:DDW crystallization system are more condensed. However, both systems are found to have a wide crystal size distribution of one stable polymorph and are thus highly useful for tunable release. More importantly, these microcrystals exhibit elongated and slow release for 14 days under an expedited release conditions model, indicating suitability for long‐term and potential localized release applications.

Precise modulation and use of reactive oxygen species for immunotherapy.

Reactive oxygen species (ROS) play an important role in regulating the immune system by affecting pathogens, cancer cells, and immune cells. Recent advances in biomaterials have leveraged this mechanism to precisely modulate ROS levels in target tissues for improving the effectiveness of immunotherapies in infectious diseases, cancer, and autoimmune diseases. Moreover, ROS-responsive biomaterials can trigger the release of immunotherapeutics and provide tunable release kinetics, which can further boost their efficacy. This review will discuss the latest biomaterial-based approaches for both precise modulation of ROS levels and using ROS as a stimulus to control the release kinetics of immunotherapeutics. Finally, we will discuss the existing challenges and potential solutions for clinical translation of ROS-modulating and ROS-responsive approaches for immunotherapy, and provide an outlook for future research.

Ultrasound-guided drug delivery system utilizing piezocatalytic MoS2 nanomaterials for anti-inflammatory therapy

Traditional drug delivery systems lack the potential of controlled drug release, thereby decreasing drug utilization and release efficiency. Herein, a next generation of stimuli-responsive drug delivery platform is designed based on piezocatalytic molybdenum disulfide nanoflowers (MoS2 NFs) which can be triggered by ultrasound (US) stimulation for effective acute inflammation therapy. Under US irradiation, MoS2 NFs undergoes piezocatalysis to generate reactive oxygen species (ROS) owing to piezoelectric polarization, thus releasing loaded anti-inflammatory drug Indomethacin (IND) to the targeted inflammation site. The cumulative release of IND elevated significantly with the increase in the duration for US exposure due to the amplified ROS generation, which displayed a highly controllable nature of the as-designed drug delivery platform. For convenient applications, the IND loaded MoS2 NFs (IND@MoS2 NFs) was functionalized onto commercial dressings and their tunable in-vivo drug release performance was demonstrated in paw edema model. IND@MoS2 NFs upon US irradiation, controllably released IND into the site-specific inflamed paw which significantly inhibited 56 % of paw swelling in 6 h by suppressing the infiltration of neutrophils and expression of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α). The highly controllable drug delivery system holds great potential in facilitating personalized, user-friendly theranostic applications with improved patient outcomes.