A highly stretchable smart dressing for wound infection monitoring and treatment.

Smart dressings integrated with bioelectronics have attracted considerable attention and become promising solutions for skin wound management. However, due to the mechanical distinction between human body and the interface of electronics, previous smart dressings often suffered obvious degradation in electrical performance when attached to the soft and curvilinear wound sites. Here, we report a stretchable dressing integrated with temperature and pH sensor for wound status monitoring, as well as an electrically controlled drug delivery system for infection treatment. The wound dressing was featured with the deployment of liquid metal for seamless connection between rigid electrical components and gold particle-based electrodes, achieving a stretchable soft-hard interface. Stretching tests showed that both the sensing system and drug delivery system exhibited good stretchability and long-term stable conductivity with the resistance change rate less than 6 % under 50 % strain. Animal experiments demonstrated that the smart dressing was capable of detecting bacterial infection via the biomarkers of temperature and pH value and the infection factors of wound were significantly improved with therapy through electrically controlled antibiotics releasing. This proof-of-concept prototype has potential to significantly improve management of the wound, especially those with dynamic strain.

MgSiO3 Fiber Membrane Scaffold with Triggered Drug Delivery for Osteosarcoma Synergetic Therapy and Bone Regeneration.

In this research, a novel MgSiO3 fiber membrane (MSFM) loaded with indocyanine green (ICG) and doxorubicin (DOX) was prepared. Because of MgSiO3's unique lamellar structure composed of a silicon-oxygen tetrahedron, magnesium ion (Mg2+) moves easily and can be further replaced with other cations. Therefore, because of the positively charged functional group of ICG, MSFM has a rather high drug loading for ICG. In addition, there is electrostatic attraction between DOX (a cationic drug) and ICG (an anionic drug). Hence, after loading ICG, more DOX can be adsorbed into MSFM because of electrostatic interaction. The ICG endows the MSFM outstanding photothermal therapy (PTT) performance, and DOX as a chemotherapeutic drug can restrain tumor growth. On the one hand, H+ exchanged with the positively charged DOX based on the MgSiO3 special lamellar structure. On the other hand, the thermal effect could break the electrostatic interaction between ICG and DOX. Based on the above two points, both tumor acidic microenvironment and photothermal effect can trigger DOX release. What's more, in vitro and in vivo antiosteosarcoma therapy evaluations displayed a superior synergetic PTT-chemotherapy anticancer treatment and excellent biocompatibility of DOX&ICG-MSFM. Finally, the MSFM was proven to greatly promote cell proliferation, differentiation, and bone regeneration performance in vitro and in vivo. Therefore, MSFM provides a creative perspective in the design of multifunctional scaffolds and shows promising applications in controlled drug delivery, antitumor performance, and osteogenesis.

Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 2: Experimental validation of the models of expansion, post-expansion mechanical strength, and drug release.

In Part 1, we have introduced expandable gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. The expansion rate, post-expansion mechanical strength, and drug release rate were modeled for a dosage form containing 200 mg nilotinib. In the present part, the dosage form was prepared and tested in vitro to validate the models. Upon immersing in a dissolution fluid, the fibrous dosage form expanded at a constant rate to a normalized radial expansion of 0.5 by 4 h, and then formed an expanded viscoelastic mass of high strength. The drug was released at a constant rate over a day. For comparison, a particle-filled gelatin capsule with the same amount of nilotinib disintegrated almost immediately, and released eighty percent of the drug content in just 10 min. The experimental data validate the theoretical models of Part 1 reasonably.

Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 1: Dosage form design, and models of expansion, post-expansion mechanical strength, and drug release.

At present, the efficacy and safety of many sparingly-soluble tyrosine kinase inhibitors (TKIs) delivered by the prevalent oral dosage forms are compromised by excessive fluctuations in the drug concentration in blood. To mitigate this limitation, in this four-part study gastroretentive fibrous dosage forms that deliver drug into the gastric fluid (and into the blood) at a controlled rate for prolonged time are presented. The dosage form comprises a cross-ply structure of expandable, water-absorbing, high-molecular-weight hydroxypropyl methylcellulose (HPMC)-based fibers coated with a strengthening, enteric excipient. The intervening spaces between the coated fibers are solid annuli of drug particles, and low-molecular-weight HPMC and enteric excipients. The central regions of the annuli are open channels. In this part, models are developed for dosage form expansion, post-expansion mechanical strength, and drug release. The models suggest that upon immersing in a dissolution fluid, the fluid percolates the open channels, diffuses into the annuli and the coated fibers, and the dosage form expands. The expansion rate is inversely proportional, and the post-expansion mechanical strength proportional to the thickness of the strengthening coating. Drug particles are released from the annuli as the surrounding excipient dissolves. The drug release rate is proportional to the concentration of low-molecular-weight HPMC at the annulus/dissolution fluid interface. The dosage forms can be readily designed for expansion in a few hours, formation of a high-strength viscoelastic mass, and drug release at a constant rate over a day.

Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 3: Theoretical models of drug concentration in blood.

In this part, drug concentration in blood after ingesting slow-release gastroretentive fibrous dosage forms and immediate-release particulate forms is modeled. The tyrosine kinase inhibitor nilotinib, which is slightly soluble in low-pH gastric fluid but practically insoluble in pH-neutral intestinal fluid is used as drug. The models suggest that upon ingestion, the fibrous dosage form expands, is retained in the stomach for prolonged time, and releases drug into the gastric fluid at a constant rate. The released drug molecules flow into the duodenum with the gastric fluid, and are absorbed by the blood. The drug is eliminated from the blood by the liver at a rate proportional to its concentration. Eventually, the elimination and absorption rates will be equal, and the drug concentration in blood plateaus out. After the gastric residence time drug absorption stops, and the drug concentration in blood drops to zero. By contrast, after administering an immediate-release particulate dosage form the drug particles are swept out of the stomach rapidly, and drug absorption stops much earlier. The drug concentration in blood rises and falls without attaining steady state. The gastroretentive fibrous dosage forms enable a constant drug concentration in blood for drugs that are insoluble in intestinal fluids.

Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 4: Experimental validation of the models of drug concentration in blood.

In this final part, the models of drug concentration in blood developed in Part 3 are validated on dogs. Both slow-release gastroretentive fibrous and immediate-release particulate dosage forms containing 200 mg nilotinib were tested. After administering, the fibrous dosage form expanded linearly with time in the stomach, to about 1.5 times the initial radius by 4 h. The expanded dosage form fractured after 10 h, and then passed into the intestines. The drug concentration in blood exhibited a broad peak with a maximum of 0.51 µg/ml and a width at half-height of 10.2 h. By contrast, after administering the immediate-release capsule the drug concentration in blood exhibited a sharp peak with a maximum of 0.68 µg/ml and a width at half-height of just 3.6 h. The experimental data validate the theoretical models reasonably. The gastroretentive fibrous dosage forms designed in this study enable a steady drug concentration in blood for increasing the efficacy and mitigating side effects of drug therapies.

Yolk-shelled silver nanowire@amorphous metal-organic framework for controlled drug delivery and light-promoting infected wound healing.

Bacteria-infected wounds healing has been greatly hindered by antibiotic resistance and persistent inflammation. It is crucial to develop multifunctional nanocomposites that possess effective antibacterial properties and can simultaneously accelerate the wound healing process to overcome the above challenges. Herein, we prepared a yolk-shell structured Ag nanowires (NWs)@amorphous hollow ZIF-67 by etching ZIF-67 onto the Ag NWs for infected wound healing for the first time. The etched hollow structure of amorphous ZIF-67 in the nanocomposite makes it a promising platform for loading healing-promoting drugs. We extensively studied the antibacterial and healing-promoting properties of the curcumin (CCM)-loaded nanocomposite (Ag NWs@C-HZ67). Ag NWs, being noble metal materials with plasmonic effects, can absorb a broad range of natural light and convert it to thermal energy. This photothermal conversion further improves the release of antibacterial components and wound healing drugs when exposed to light. During the healing process of an infected wound, Ag and Co ions were released from Ag NWs@C-HZ67 upon direct contact with the wound exudate and under the influence of light irradiation. Simultaneously, the loaded CCM leaked out to repair the infected wound. The minimum inhibitory concentrations of the Ag NWs@C-HZ67 groups against Escherichia coli and Staphylococcus aureus bacteria decreased to 3 and 3 µg ml-1 when exposed to white light. Furthermore, an in vivo assessment of infected wound healing demonstrated that combining Ag NWs@C-HZ67 with light significantly accelerated the wound healing process, achieving 70% healing by the 6th day and almost complete healing by the 8th day. This advanced nanocomposite, consisting of components that possess antibacterial and growth-promoting properties, offers a safe, effective and clinically-translatable solution for accelerating the healing process of infected wounds.

Evaluation of microwave irradiated Polyacrylamide grafted Opuntia leaf mucilage graft copolymer (OPM-g-PAM) as effective controlled release polymer for release of Rosuvastastin as model drug.

Controlled drug delivery systems offer numerous advantages. This research evaluates Opuntia leaf mucilage grafted with polyacrylamide (OPM-g-PAM) as a promising controlled-release polymer. PAM chains were grafted onto the backbone of OPM using a microwave-assisted method. Optimization of the best grade was based on % grafting efficiency and intrinsic viscosity, followed by extensive physical and analytical characterizations. Analytical characterizations revealed semicrystalline nature of the biomaterial. SEM and AFM observations revealed rough and porous surfaces, indicating effective grafting. Swelling behavior showed maximum sensitivity at pH 7, with reduced swelling at higher sodium chloride concentrations. A comparative study of % drug release of Rosuvastatin over 24 h showed that the optimized grade controlled drug release effectively, achieving 78.5 % release compared to 98.8 % for GF-3. The release data fitted the Korsmeyer-Peppas model, with an "n" value of 0.8334, indicating non-Fickian (anomalous) diffusion. Bacterial biodegradability studies confirmed the high biodegradability of the graft copolymer. In vitro acute toxicity tests showed no toxicity, as confirmed by histopathological studies of heart, liver, and kidney. Overall, the results indicate that OPM-g-PAM is a highly promising material for use in drug delivery systems, demonstrating potential as a novel controlled-release polymer.

New Zein Protein Composites with High Performance in Phosphate Removal, Intrinsic Antibacterial, and Drug Delivery Capabilities.

Herein, poly(N-(4-aminophenyl)methacrylamide)-carbon nano-onions [abbreviated as PAPMA-CNOs (f-CNOs)] integrated gallic acid cross-linked zein composite fibers (ZG/f-CNOs) were developed for the removal/recovery of phosphate from wastewater along with controlled drug delivery and intrinsic antibacterial characteristics. The composite fibers were produced by Forcespinning followed by a heat-pressure technique. The obtained ZG/f-CNOs composite fibers presented several favorable characteristics of nanoadsorbents and drug carriers. The composite fibers exhibited excellent adsorption capabilities for phosphate ions. The adsorption assessment demonstrated that composite fibers process highly selective sequestration of phosphate ions from polluted water, even in the presence of competing anions. The ZG/f-CNOs composite fibers presented a maximum phosphate adsorption capacity (qmax) of 2500 mg/g at pH 7.0. This represents the most efficient phosphate adsorption system among all of the reported nanocomposites to date. The isotherm studies and adsorption kinetics of the adsorbent showed that the adsorption experiments followed the pseudo-second-order and Langmuir isotherm model (R2 = 0.9999). After 13 adsorption/desorption cycles, the adsorbent could still maintain its adsorption efficiency of 96-98% at pH 7.0 while maintaining stability under thermal and chemical conditions. The results mark significant progress in the design of composite fibers for removing phosphates from wastewater, potentially aiding in alleviating eutrophication effects. Owing to the f-CNOs incorporation, ZG/f-CNOs composite fibers exhibited controlled drug delivery. An antibiotic azithromycin drug-encapsulated composite fibers presented a pH-mediated drug release in a controlled manner over 18 days. Furthermore, the composite fibers displayed excellent antibacterial efficiency against Gram-positive and Gram-negative bacteria without causing resistance. In addition, zein composite fibers showed augmented mechanical properties due to the presence of f-CNOs within the zein matrix. Nonetheless, the robust zein composite fibers with inherent stimuli-responsive drug delivery, antibacterial properties, and phosphate adsorption properties can be considered promising multifunctional composites for biomedical applications and environmental remediation.

Polymeric Nanoparticles for Wound Healing.

Skin injury is one of the most prevalent lesions in humans, and many such wounds, including deep burns and chronic skin wounds, are notoriously difficult to heal. It has been established by medical practitioners that current wound therapies are not perfectly effective and are far from satisfactory. Meanwhile, nanotechnologies have made it possible to develop pharmaceutical formulations that can elevate the effectiveness of conventional pharmacotherapies to entirely new heights. Most nanostructured biomaterials used to treat wounds, including those that have helped establish this fascinating subject, have been polymeric. The bibliographic analysis presented here shows a steady growth in the research output of studies on the use of polymeric nanoparticles in wound healing therapies. This article provides an overview of polymeric nanoparticles for the treatment of wounds with an emphasis on different chemistries and polymer-drug combinations that have been proven the most effective. The wound age, pathophysiology, wound healing treatments of the present and past, as well as the physicochemical nature and methods for the synthesis of polymeric nanoparticles, are all covered in the opening parts of the review. The existing polymeric nano-drug delivery systems with the greatest promise for wound healing and skin regeneration are subsequently addressed and their potentials summarized.

Comparative study of iontophoresis-assisted transdermal delivery of bupivacaine and lidocaine as anesthetic drugs.

Postoperative pain management is an important aspect of the overall surgical care process. Effective pain management not only provides patient comfort but also promotes faster recovery and reduces the risk of complications. Bupivacaine (BUP) and Lidocaine (LID) transdermal drug deliveries via thermoplastic polyurethane matrix (TPU) and iontophoresis technique are proposed here as alternative routes for postoperative pain instead of the injection route. Under applied electric field, the amounts of BUP and LID released were 95% and 97% from the loaded amounts, which were higher than the passive patch of 40%. The time to equilibrium of BUP turned out to be faster than the time to equilibrium of LID by approximately 1.5 times. This was due to 2 factors namely the drug molecular weight and the drug pKa value; they play an important role in the selection of a suitable drug for fast-acting or long-acting for the postoperative patients. By using this transdermal patch via iontophoresis system, BUP was deemed as the suitable drug for fast-acting due to the shorter time to equilibrium, whereas LID was the suitable drug for long-acting. The in-vitro drug release - permeation study through a porcine skin indicated the efficiency and potential of the system with the amounts of drug permeated up to 76% for BUP and 81% for LID. The TPU transdermal system was demonstrated here as potential to deliver BUP and LID for postoperative patients.

Effects of montmorillonite on the loading and release of Piper betle L. extract applied for wound dressing based on chitosan/polyvinyl alcohol.

In this study, we investigate the influence of montmorillonite (MMT) on the loading and release of Piper betle L. extract (PLE)-a medicinal herb containing active secondary metabolites with antibacterial, antioxidant, and anti-inflammatory effects. MMT (1 %, 3 %, 5 %) was blended into the chitosan/polyvinyl alcohol (CS/PVA) biocomposite film by the solution evaporation method, and then PLE was loaded onto this biocomposite using the immersion method. The tensile strength and the ability to absorb exudates of the CS/PVA film improved with the increase in MMT content. The MMT 3 % film was considered to have the best properties: good mechanical properties with a tensile strength of 27.44 ± 0.27 MPa and elongation at break of 14.57 ± 0.30 %, potential for wound dressing due to its ability to absorb wound exudate (swelling degree 61.70 ± 0.30 %) and a suitable water vapor transmission rate (1999 ± 47 g/m2·d). The presence of MMT (1 %, 3 %, 5 %) in the CS/PVA film led to an increase in the PLE loading efficiency of the films compared to the film without MMT, up to 1.65, 1.73, and 1.87 times, respectively. The MMT 3 % and 5 % films also exhibited a sustained PLE release effect for up to 24 h. MMT increased PLE bioavailability through bioactivity tests: antibacterial activity against both E. coli and S. aureus, antioxidant activity, effective healing of 2nd-degree burn wounds, and biocompatibility with the L929 fibroblasts cell line. The combination of physicochemical properties and biological activities proved that the MMT/PLE drug delivery system based on the CS/PVA biocomposite is promising for wound dressing.

Development and characterization of pH-responsive Delonix regia/mucin co-poly (acrylate) hydrogel for controlled drug delivery of metformin HCl.

This study introduces a pH-responsive hydrogel developed from Delonix regia and mucin co-poly(acrylate) through free radical polymerization to enhance controlled drug delivery systems. Characterization using FTIR, DSC, TGA, SEM, PXRD, and EDX spectroscopy detailed the hydrogel's amorphous and crystalline structures, thermal stability, surface characteristics, and elemental composition. Tested at a pH of 7.4-mimicking intestinal conditions-the hydrogel demonstrated significant swelling, indicating its capability for targeted drug release. With Metformin HCl as a model drug, the hydrogel exhibited a promising sustained release profile, underscoring its potential for oral administration. Safety and biocompatibility were assessed through acute oral toxicity studies in albino rabbits, encompassing biochemical, hematological, and histopathological evaluations. X-ray imaging confirmed the hydrogel's navigability through the gastrointestinal tract, affirming its application in drug delivery. By potentially mitigating gastrointestinal side effects, enhancing patient compliance, and improving therapeutic efficacy, this Delonix regia/mucin co-poly(acrylate) hydrogel represents a step in pharmaceutical sciences, exploring innovative materials and methodologies for drug delivery.

Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury.

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood-brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

The contemplation of amylose for the delivery of ulcerogenic nonsteroidal anti-inflammatory drugs.

This manuscript proposes an innovative approach to mitigate the gastrointestinal adversities linked with nonsteroidal anti-inflammatory drugs (NSAIDs) by exploiting amylose as a novel drug delivery carrier. The intrinsic attributes of V-amylose, such as its structural uniqueness, biocompatibility and biodegradability, as well as its capacity to form inclusion complexes with diverse drug molecules, are meticulously explored. Through a comprehensive physicochemical analysis of V-amylose and ulcerogenic NSAIDs, the plausibility of amylose as a protective carrier for ulcerogenic NSAIDs to gastrointestinal regions is elucidated. This review further discusses the potential therapeutic advantages of amylose-based drug delivery systems in the management of gastric ulcers. By providing controlled release kinetics and enhanced bioavailability, these systems offer promising prospects for the development of more effective ulcer therapies.

Spray-Dried Chitosan Hydrogel Particles as a Potential Delivery System for Benzydamine Hydrochloride.

Chitosan, being a biocompatible and mucoadhesive polysaccharide, is one of the most preferred hydrogel-forming materials for drug delivery. The objectives of the present study are to obtain spray-dried microparticles based on low-molecular-weight chitosan and study their potential application as cargo systems for the orally active drug benzydamine hydrochloride. Three types of particles are obtained: raw chitosan particles (at three different concentrations), cross-linked with sodium tripolyphosphate (NaTPP) particles (at three different chitosan:NaTPP ratios), and particles coated with mannitol (at three different chitosan:mannitol ratios), all of them in the size range between 1 and 10 µm. Based on the loading efficiency and the yields of the formulated hydrogel particles, one model of each type is chosen for further investigation of the effect of the cross-linker or the excipient on the properties of the gel structures. The morphology of both empty and benzydamine hydrochloride-loaded chitosan particles was examined by scanning electron microscopy, and it was quite regular and spherical. Interactions and composition in the samples are investigated by Fourier-transformed infrared spectroscopy. The thermal stability and phase state of the drug and drug-containing polymer matrixes were tested by differential scanning calorimetry and X-ray powdered diffraction, revealing that the drug underwent a phase transition. A drug release kinetics study of the chosen gel-based structures in simulated saliva buffer (pH = 6.8) and mathematical modeling of the process were performed, indicating the Weibull model as the most appropriate one.

Polyelectrolyte complexes based on a novel and sustainable hemicellulose-rich lignosulphonate for drug delivery applications.

Polyelectrolyte complexes (PECs) are polymeric structures formed by the self-assembly of oppositely charged polymers. Novel biomaterials based on PECs are currently under investigation as drug delivery systems, among other applications. This strategy leverages the ability of PECs to entrap drugs under mild conditions and control their release. In this study, we combined a novel and sustainably produced hemicellulose-rich lignosulphonate polymer (EH, negatively charged) with polyethyleneimine (PEI) or chitosan (CH, positively charged) and agar for the development of drug-releasing PECs. A preliminary screening demonstrated the effect of several parameters (polyelectrolyte ratio, temperature, and type of polycation) on PECs formation. From this, selected formulations were further characterized in terms of thermal properties, surface morphology at the microscale, stability, and ability to load and release methylene blue (MB) as a model drug. EH/PEI complexes had a more pronounced gel-like behaviour compared to the EH/CH complexes. Differential scanning calorimetry (DSC) results supported the establishment of polymeric interactions during complexation. Overall, PECs' stability was positively affected by low pH, ratios close to 1:1, and the addition of agar. PECs with higher EH content showed a higher MB loading, likely promoted by stronger electrostatic interactions. The EH/CH formulation enriched with agar showed the best sustained release profile of MB during the first 30 h in a pH-dependent environment simulating the gastrointestinal tract. Overall, we defined the conditions to formulate novel PECs based on a sustainable hemicellulose-rich lignosulphonate for potential applications in drug delivery, which promotes the valuable synergy between sustainability and the biomedical field.

Selectively coated contact lenses by nanoelectrospray (nES) to fabricate drug-eluting contact lenses for treating ocular diseases.

Drug-eluting contact lenses (DECLs) incorporated with poly(lactic-co-glycolic acid) (PLGA) and various model drugs (ketotifen fumarate, bimatoprost and latanoprost) were fabricated using nanoelectrospray (nES) approach. The resulting DECLs demonstrated outstanding optical transmittance within the optical zone, indicating that the employed coating procedure did not compromise visual acuity under the prescribed spraying parameters. In vitro drug release assessments of the model drugs (ketotifen fumarate (KF), bimatoprost (BIM), and latanoprost (LN)) revealed a strong correlation between the model drug's hydrophobicity and the duration of drug release. Changing the drug loading of the more hydrophilic model drugs, BIM and KF, showed no impact on the drug release kinetics of DECLs loaded with BIM and KF. However, for the hydrophobic model drug, LN, the highest LN loading led to the most extended drug release. The conventional steam sterilisation method was found to damage the PLGA coating on the DECLs fabricated by nES. An alternative sterilisation strategy, such as radiation sterilisation may need to be investigated in the future study to minimise potential harm to the coating.

Organophosphate Detoxification and Acetylcholinesterase Reactivation Triggered by Zeolitic Imidazolate Framework Structural Degradation.

Organophosphate (OP) toxicity is related to inhibition of acetylcholinesterase (AChE) activity, which plays a key role in the neurotransmission process. In this work, we report the ability of different zinc zeolitic imidazolate frameworks (ZIFs) to behave as potential antidotes against OP poisoning. The Zn-L coordination bond (L = purine, benzimidazole, imidazole, or 2-methylimidazole) is sensitive to the G-type nerve agent model compounds diisopropylfluorophosphate (DIFP) and diisopropylchlorophosphate, leading to P-X (X = F or Cl) bond breakdown into nontoxic diisopropylphosphate. P-X hydrolysis is accompanied by ZIF structural degradation (Zn-imidazolate bond hydrolysis), with the concomitant release of the imidazolate linkers and zinc ions representing up to 95% of ZIF particle dissolution. The delivered imidazolate nucleophilic attack on the OP@AChE adduct gives rise to the recovery of AChE enzymatic function. P-X bond breakdown, ZIF structural degradation, and AChE reactivation are dependent on imidazolate linker nucleophilicity, framework topology, and particle size. The best performance is obtained for 20 nm nanoparticles (NPs) of Zn(2-methylimidazolate)2 (sod ZIF-8) exhibiting a DIFP degradation half-life of 2.6 min and full recovery of AChE activity within 1 h. 20 nm sod ZIF-8 NPs are not neurotoxic, as proven by in vitro neuroblastoma cell culture viability tests.

Chitosan nanoparticles laden contact lenses for enzyme-triggered controlled delivery of timolol maleate: A promising strategy for managing glaucoma.

To improve drug bioavailability, eye drops can be replaced by drug-eluting contact lenses. However, issues of drug leaching from lenses during manufacture and storage, and sterilization, currently limit their commercial application. To address the issues, stimuli-(lysozyme)-sensitive chitosan nanoparticles were developed to provide controlled ocular drug delivery. Nanoparticles were prepared by ionic gelation and characterized by TEM, X-ray diffraction, DSC, and FTIR. In the flux study, conventional-soaked contact lenses (SM-TM-CL) showed high-burst release, while with direct drug-only laden contact lenses (DL-TM-CL) the drug was lost during extraction and sterilization, as well as having poor swelling and optical properties. The nanoparticle-laden contact lenses (TM-Cht-NPs) showed controlled release of timolol for 120 h in the presence of lysozyme, with acceptable opto-physical properties. In the shelf-life study, the TM-Cht-NPs contact lenses showed no leaching or alteration in the drug release pattern. In animal studies, the TM-NPs-CL lenses gave a high drug concentration in rabbit tear fluid (mean = 11.01 µg/mL for 56 h) and helped maintain a low intraocular pressure for 120 h. In conclusion, the chitosan nanoparticle-laden contact lenses demonstrated the potential application to treat glaucoma with acceptable opto-physical properties and addressed the issues of drug-leaching during sterilization and storage.