Drug Delivery Applications Research Articles

Electrospinning Recombinant Spider Silk Fibroin-Reinforced PLGA Membranes: A Biocompatible Scaffold for Wound Healing Applications.

Polylactide-polyglycolide (PLGA) is one of the most attractive polymeric biomaterials used to fabricate medical devices for drug delivery and tissue engineering applications. Nevertheless, the utilization of PLGA in load-bearing applications is restricted due to its inadequate mechanical properties. This study examines the potential of recombinant silk fibroin (eADF4), a readily producible biomaterial, as a reinforcing agent for PLGA. The PLGA/eADF4 composite membranes were developed by using the process of electrospinning. The spinnability of the electrospinning solutions and the physicochemical, mechanical, and thermal properties of the composite membranes were characterized. The addition of eADF4 increased the viscosity of the electrospinning solutions and enhanced both the mechanical characteristics and the thermal stability of the composites. This study demonstrates that PLGA membranes reinforced with recombinant spider silk fibroin are noncytotoxic, significantly enhance cell migration and wound closure, and do not trigger an inflammatory response, making them ideal candidates for advanced wound healing applications.

Synthesis Techniques and Biomedical Applications of Cyclodextrin Metal-Organic Frameworks.

Cyclodextrin Metal-Organic Frameworks (CD MOFs) represent an innovative class of materials with remarkable properties and a broad range of applications. This review provides a comprehensive overview of the synthesis techniques, structural characterization, and diverse applications of CD-MOFs. By combining cyclodextrins (CDs) with metal-organic frameworks (MOFs), CD-MOFs are developed with enhanced functionality. The synthesis methods, including various metal sources, coordination modes, and post-synthesis modifications, are discussed alongside advanced structural characterization techniques like X-ray crystallography and spectroscopic methods. The unique characteristics of CD-MOFs, such as high specific surface area, tunable porosity, and customizable chemical structure, make them exceptional candidates for applications in gas adsorption, drug delivery, catalysis, sensing, and environmental remediation. Notably, CD-MOFs show significant promise as nanocarriers in drug delivery systems, offering improved therapeutic outcomes due to their efficient encapsulation and controlled release capabilities. The review highlights recent advancements and underscores the potential impact of CD-MOFs in driving future innovations across various scientific fields.

Substituted Maleimides: Self-Reportable Linkers and Tags in Bioconjugation, Materials Science, and Nanotechnology.

Substituted maleimides are customisable fluorescent linkers and probes with adaptable reactivity and optical properties. Their compact nature and tunability has led to their use in various applications. For example, their solvatochromic properties offer real-time feedback on linking chemistry and environmental changes, essential for applications in material labelling, drug delivery, and nanoparticle functionalisation. This review focusses on developing, synthesising, and modifying substituted maleimides as environment-sensitive fluorescent linkers and probes. It delves into their photophysical dynamics and strategic applications, highlighting their significant contributions to macromolecule conjugation and the development of self-reporting materials.

Chromatography and Spectroscopic Technique-Based Rapid Characterization of Nano-Carrier Pharmaceuticals.

A nanocarrier is a novel colloidal system whose particle size ranges between 1-100 nm. It is extensively utilized in drug delivery and various other sectors, such as the pharmaceutical, food, and dairy industries. The nanocarrier systems, including solid lipid nanoparticles, micelles, liposomes, and other encapsulated compounds, have improved stability, solubility, bioavailability, and quality. Nanocarriers offer therapeutic effectiveness with low toxicity because of their biocompatibility and ability to cross body barriers. Various analytical techniques, such as chromatography and spectroscopy, are crucial in qualitative and quantitative analysis of nanocarrier-based formulations. Molecular identification and drug content determination require chromatographic techniques, particularly HPLC. Spectroscopic techniques such as LC-MS, NMR, GC-MS, CE-MS, Raman, and IR are used to analyze the interaction and molecular structure of the sample. Nanocarriers have several benefits but face various challenges like stability, drug loading, regulatory standards, and biocompatibility. Future surface engineering and nanocarrier design advancements could improve targeted drug delivery and sustained diagnostic applications, significantly impacting healthcare.

Magnetic resonance cavitation imaging for the monitoring of ultrasound therapies

Objective.Focused ultrasound (FUS) is a promising non-invasive therapeutic approach that can be used to generate thermal and non-thermal bioeffects. Several non-thermal FUS therapies rely on FUS-induced oscillations of microbubbles (MBs), a phenomenon referred to as cavitation. Cavitation monitoring in real time is essential to ensure both the efficacy and the safety of FUS therapies. This study aims to introduce a new magnetic resonance (MR) method for cavitation monitoring during FUS therapies.Approach.By finely synchronizing the FUS pulse with an accelerated turbo spin-echo MR sequence, the cavitation effect could be quantitatively estimated on the acquired images at 1-Hz refresh rate. The proposed method was assessed in vitro in a water bath. A series of FUS pulses were generated on a silicone tube filled with MBs at different acoustic pressures (0.07-2.07 MPa) and pulse durations (20-2000μs). MR images and passive cavitation detection (PCD) signals were simultaneously acquired for each FUS pulse.Main results.Inertial cavitation was found to induce a quantitatively interpretable signal loss on the MR image. The transition from stable to inertial cavitation was identified on MR cavitation maps with high repeatability. These results were found to be in good agreement with PCD measurements in terms of pressure thresholds between stable and inertial cavitation. MR cavitation imaging was shown to be sensitive to short and even ultrashort FUS pulses, from 2 ms down to 20μs. The presented theoretical model suggests that the signal loss in MR cavitation imaging relies on susceptibility changes related to the diameter of the oscillating MBs.Significance.The proposed MR cavitation imaging method can both locate and characterize cavitation activity. It has therefore the potential to improve the efficacy and safety of FUS therapies, particularly for localized drug delivery applications.

Chitosan-melanin complex microsphere: A potential colonic delivery system for protein drugs

The characteristics and performance of chitosan-based colon delivery systems are significantly influenced by the method of preparation. Insect chitosan-melanin complex (CMC) may offer superior attributes over traditional shrimp and crab chitosan (CS) for colon-targeted administration. This study used dung beetle CMC as the carrier matrix and comprehensively examined the impact of various crosslinking techniques on the colonic drug delivery efficacy of microspheres, encompassing drug loading, swelling, drug release behavior, adhesion, enzymatic degradation, and absorption enhancement. The results indicate that F-TPPLC microspheres, crosslinked with a combination of formaldehyde and sodium tripolyphosphate, exhibit superior drug loading capabilities, optimal swelling behavior, and controlled in vitro drug release profiles in the colonic environment, along with excellent adhesion and enzymatic degradation properties within intestinal tract. Notably, these F-TPPLC microspheres increase paracellular permeability, possibly by disrupting the calcium-dependent adhesion junctions. In comparison to commercial CS, CMC demonstrates superior drug encapsulation efficiency, enhanced colonic drug release, adhesion, and absorption promotion, rendering it a favorable candidate as a carrier in colon-targeted drug delivery systems. Consequently, F-TPPLC microspheres derived from CMC are highly suitable for colon drug delivery applications and show promising potential for the oral delivery of peptide and protein-based therapeutics to the colon.

Activated carbon-coated iron oxide magnetic nanocomposite (IONPs@CtAC) loaded with morin hydrate for drug-delivery applications.

Cancer is a major disease that affects millions of people around the world every year. It affects individuals of all ages, races, and backgrounds. Since drugs used to treat cancer cannot distinguish between cancerous and healthy cells, they cause systemic toxicity along with serious side effects. Recently, controlled drug-release systems have been developed to reduce the side effects caused by anticancer drugs used for treatment. Morin is an anticancer drug with a flavonol structure. It has been extensively researched for its antioxidant, anti-inflammatory, antitumoral, and antibacterial properties, especially found in Chinese herbs and fruits, and its multiple positive effects on different diseases. In this study, a nanocomposite with magnetic properties was synthesized by coating biocompatible activated carbon obtained using the fruits of the Celtis tournefortii plant on the surface of iron oxide magnetic nanoparticles. Characterization of the synthesized activated carbon-coated iron oxide magnetic nanocomposite was confirmed by Fourier transform infrared, scanning electron microscopy, energy-dispersive X-ray spectrometry, X-ray diffraction, dynamic light scattering, zeta potential, and vibrating sample magnetometry. The cytotoxic effects of the drug-loaded magnetic nanocomposite were examined in HT-29 (colorectal), T98-G (glioblastoma) cancer cell lines, and human umbilical vein endothelial cell (HUVEC) healthy cell line. The morin loading and release behavior of the activated carbon-coated iron oxide magnetic nanocomposite were studied, and the results showed that up to 60% of the adsorbed morin was released within 4h. In summary, activated carbon-coated iron oxide magnetic nanocomposite carriers have shown promising results for the delivery of the morin drug.

Hydrogel-Embedded Polydimethylsiloxane Contact Lens for Ocular Drug Delivery.

Topical administration is the commonly preferred method of administering ophthalmic formulations, with the majority of available medications in the form of eye drops or ointments. However, the topical application of ophthalmological medications has less bioavailability and a short residence time because of the physiological and anatomical constraints of the eye, making efficient ophthalmic drug delivery a challenging task. Microfluidic contact lenses have the advantage of delivering drugs into the eye in a controlled and on-demand manner. Here, we showcase the use of hydrogel-embedded microcavities on PDMS-based contact lenses for ocular drug delivery applications. The fabrication technique adopted here is the spontaneous formation of the spherical cavity by hydrogel monomer droplet, followed by the simultaneous thermal curing of hydrogel and PDMS, creating a spherical cavity as small as 150 μm. The spherical cavity is embedded with pH-responsive hydrogel for on-demand drug delivery. The drug loaded in the hydrogel matrix is released into the ocular environment by diffusion. The spherical cavity with a narrow opening restricts the diffusion to a minimum under normal ocular pH conditions(pH > 6). When the ocular pH reduces (pH < 6), the pH-responsive hydrogel inside the spherical cavity deswell and accelerates the drug release.

Denaturants and Solutol® HS15 in ophthalmic formulations: Insights into their combined effects

In the field of ophthalmology, significant attention is dedicated to developing micellar carriers to enhance ocular drug delivery. Urea is a well-known denaturant and has been used as an excipient in several ocular formulations due to its efficacy as an ocular hypotensive agent. The presence of urea as an excipient may influence the characteristics of the micellar nanocarrier in the formulation and needs to be investigated. Solutol® HS15, a well-known nonionic surfactant and a commonly used nanocarrier in drug formulations, enhances the solubilization and stability of ocular drugs. However, a detailed study of its interaction with various pharmaceutical excipients is still lacking. With this intention, the present study focuses on comprehending the interaction between Solutol® HS15 micelles with urea and its derivatives. Here, we present a detailed analysis on the influence of urea and its derivatives (methylurea, dimethylurea) on Solutol® HS15 using small-angle neutron scattering (SANS), dynamic light scattering (DLS), and cloud point (CP) measurements. The presence of urea and its derivatives strongly affects the CP, leading to a significant increase in its values when urea derivatives are present. Additionally, the SANS and DLS results also indicate a significant decrease in micellar size, suggesting demicellization. The observed effects of urea derivatives on Solutol® HS15 micelles underscore the importance of considering solvent-surfactant interactions in understanding the behavior of surfactant-based systems. This research will provide greater insight into the interactions between urea and its derivatives and Solutol® HS15, which will assist in understanding the morphology and size distribution of surfactant micelles for drug delivery applications.

Distinct Solubilization Mechanisms of Medroxyprogesterone in Gemini Surfactant Micelles: A Comparative Study with Progesterone

The solubilization behavior of medroxyprogesterone (MP) within gemini surfactant micelles (14-6-14,2Br−) was investigated and compared with that of progesterone to uncover distinct solubilization mechanisms. We employed 1H-NMR and 2D ROESY spectroscopy to elucidate the spatial positioning of MP within the micelle, revealing that MP integrates more deeply into the micellar core. This behavior is linked to the unique structural features of MP, particularly its 17β-acetyl group, which promotes enhanced interactions with the hydrophobic regions of the micelle, while the 6α-methyl group interacts with the hydrophilic regions of the micelle. The 2D ROESY correlations specifically highlighted interactions between the hydrophobic chains of the surfactant and two protons of MP, H22 and H19. Complementary machine learning and electron density analyses supported these spectroscopic findings, underscoring the pivotal role of the molecular characteristics of MP in its solubilization behavior. These insights into the solubilization dynamics of MP not only advance our understanding of hydrophobic compound incorporation in gemini surfactant micelles but also indicate the potential of 14-6-14,2Br− micelles for diverse drug delivery applications.

Unveiling Fluorescence Spectroscopy, Molecular Docking and Dynamic Simulations: Interactions Between Protein and 2, 4-Dinitrophenylhydrazine Schiff Base.

In this study, we aimed to explore the interaction mechanism between bovine serum albumin (BSA) and a Schiff base compound derived from 2,4-dinotrophenyl hydrazine (L) using various spectroscopic techniques. The interaction between BSA and synthesizing molecule can provide insights into binding affinity, conformational changes and potential applications in drug delivery or biochemistry. The interaction between BSA and L was studied by using UV-Vis and fluorescence titration analysis. The fluorescence quenching emission was observed at 343nm, upon addition of L to the buffer solution of BSA. The binding between BSA and ligand is static in nature using fluorescence quenching emission. The thermodynamic parameters were calculated from the temperature-dependent binding constants (i.e., ∆H = -0.318kcal/mol, ∆G = -7.857kcal/mol and ∆S = 0.023kcal/mol), which indicated that the protein-ligand complex formation between L and BSA is mainly due to the electrostatic interactions. The experimental and theoretical results showed excellent agreement with respect to the mechanism of binding and binding constants. The molecular docking and molecular dynamic analysis experiments were performed to establish the interaction between protein and ligand.

Aminosilane@mesoporoussilica/chitosan∗salicylaldehyde nanohybrid: synthesis, characterization and applications

“Hydrogen-borrowing” mechanism has enables the production of biologically active molecules with minimal waste, high efficiency and mild reaction conditions. However, majority of research on the above mechanism has been focused on small molecule transformations. Hence, using Fe-tetraphenylcyclopentadienone tricarbonyl complex as a catalyst for “hydrogen-borrowing” mechanism between amines and alcohols, a novel pH-responsive inorganic-organic hybrid nanocarrier based on mesoporous silica-chitosan (MSN@CONH2/CS∗SCA) was developed to overcome these limitations. The nanocarrier was fabricated through C-N bond formation between 1-[3-trimethoxysiliylpropyl] urea functionalized mesoporous silica and salicylaldehyde modified chitosan derivative for antibacterial, antioxidant and drug delivery application. The chemical composition of synthesized nanocarrier was characterized by FTIR, 1H NMR and XRD techniques while the thermal stability examined through TGA. The surface morphology and porosity were evaluated using BET, SEM, and TEM whereas elemental composition, particle size and surface charge were determined by EDX with mapping, PSA and Zeta-potential method respectively. The nanohybrid was loaded with quercetin and curcumin drug, with 82.68 % and 83.24 % encapsulation efficiency respectively. The controlled drug release for quercetin was observed with 76 % (pH-5.0) and 20 % (pH-7.4), while for curcumin it observed 70.36 % (pH-5.0) and 19.16 % (pH-7.4) in 72 h. The antibacterial performance of nanocarrier shows better zone of inhibition for E. coli [2.9 ± 0.2 cm(3)] as compared to B. subtilis [1.6 ± 0.3 cm(3)]. The antioxidant ability of nano-hybrid to scavenge DPPH and ABTS radicals were 53.18 % and 55.21 %, respectively. Thereafter, MTT cytotoxicity assay of nanohybrid on peripheral blood mononuclear cells) exhibited promising results for biomedical applications.

Kinetic and thermodynamic analysis of engineered alginate–chitosan hydrogel based scaffolds for drug delivery applications

The synthesis of stimulus–responsive hydrogel–based scaffolds has been extensively investigated for controlled drug delivery applications. This study focused on synthesizing alginate and chitosan–based scaffolds for potential use in releasing antibiotic antimycotic solution (AAS) drugs. The controlled release of AAS from AAS–loaded alginate–chitosan scaffolds was investigated under distinct temperatures viz. 37 °C, 25 °C, and 10 °C, labeled as scaffolds A, B, and C, respectively. Porosity assessment revealed consistent and substantial mean porosity percentage of 95.06 ± 2.01 % across all scaffolds. The lower temperature of 10 °C significantly contributed to a gradual and consistent cumulative release of 91.67 ± 1.47 %, compared to 37 °C (94.07 ± 1.89 %) and 25 °C (92.75 ± 1.51 %). The Korsmeyer–Peppas model exhibited high R2 values (0.98, 0.97 to 0.99) for scaffolds A, B, and C, indicating its suitability for describing the in–vitro release of AAS. Furthermore, the obtained release exponent values (0.60, 0.65, and 0.72 for scaffolds A, B, and C, respectively) suggest non–Fickian diffusion as the primary mechanism governing drug release. The release was also pH–dependent, with slower release at acidic (pH 3) and faster release under basic conditions (pH 8) due to varying swelling ratios. Evaluation of thermodynamic parameters viz. Ea, ΔG, ΔH and ΔS, using the rate constant of the Korsmeyer–Peppas model, revealed positive values of ΔH > 0 and ΔS > 0, indicating the prevalence of hydrophobic interactions in the release process.

Form Equals Function: Influence of Coacervate Architecture on Drug Delivery Applications.

Complex coacervates, formed through electrostatic interactions between oppositely charged polymers, present a versatile platform for drug delivery, providing rapid assembly, selective encapsulation, and responsiveness to environmental stimuli. The architecture and properties of coacervates can be tuned by controlling structural and environmental design factors, which significantly impact the stability and delivery efficiency of the drugs. While environmental design factors such as salt, pH, and temperature play a crucial role in coacervate formation, structural design factors such as polymer concentration, polymer structure, mixing ratio, and chain length serve as the core framework that shapes coacervate architecture. These elements modulate the phase behavior and material properties of coacervates, allowing for a highly tunable system. In this review, we primarily analyze how these structural design factors contribute to the formation of diverse coacervate architecture, ranging from bulk coacervates to polyion complex micelles, vesicles, and cross-linked gels, though environmental design factors are considered. We then examine the effectiveness of these architectures in enhancing the delivery and efficacy of drugs across various administration routes, such as noninvasive (e.g., oral and transdermal) and invasive delivery. This review aims to provide foundational insights into the design of advanced drug delivery systems by examining how the origin and chemical structure of polymers influence coacervate architecture, which in turn defines their material properties. We then explore how the architecture can be tailored to optimize drug delivery for specific administration routes. This approach leverages the intrinsic properties derived from the coacervate architecture to enable targeted, controlled, and efficient drug release, ultimately enhancing therapeutic outcomes in precision medicine.

Conformations of α-cyclodextrin and its role on the stability of inclusion complexes in aqueous solution

α-Cyclodextrin (αCD), a cyclic carbohydrate polymer, presents a wealth of opportunities for drug delivery and various industrial applications. Its high affinity and selectivity in encapsulating target molecules have been well-documented. However, the influence of αCD's conformational variations on its encapsulation capacity remains a promising area for further exploration. This study explores the conformational dynamics of αCD and its relationship with the formation of inclusion complexes (ICs) in aqueous solutions, focusing on understanding the forces driving these dynamics and the formation of stable ICs. Classical molecular dynamics (CMD) demonstrate that αCD solvated in water can adopt two conformations: a truncated cone shape with a suitable cavity for encapsulation and a distorted cone shape with a collapsed cavity. The predominant conformation observed in the CMD trajectory of pristine αCD is the distorted cone. However, under complexation conditions with aliphatic molecules, the guest molecule's size dictates the ICs' stability, forcing αCD to maintain the truncated cone conformation. Quantum chemistry methods and electron density analyses (Quantum Theory of Atoms in Molecules and Non-Covalent Interactions index) support CMD observations by characterizing and quantifying non-covalent interactions. Findings indicate that the shift from the truncated to the distorted cone conformation in αCD is primarily driven by intramolecular non-covalent interactions and the reconfiguration of water molecules surrounding αCD. The ICs' analysis displays a significant correlation between the size of the aliphatic chain and the intensity of intermolecular interactions. The strength of these interactions can effectively disrupt the αCD intramolecular non-covalent interactions that lead to a conformational change and, consequently, the loss of the inclusion complex. In conclusion, although αCD's conformational change can affect encapsulation, guest molecules can manipulate the conformational preference. The systematic analysis of non-covalent interactions offers a way to characterize and quantify these forces, enhancing our ability to understand and predict the stability of inclusion complexes.

Mechanistic Model for Drug Release from PLGA-Based Biodegradable Implants for In Vitro Release Testing: Development and Validation.

Several factors can affect drug release from polylactide coglycolide (PLGA)-based formulations, including polymer and drug properties, formulation components, manufacturing processes, and environmental in vitro or in vivo conditions. To achieve optimal release profiles for specific drug delivery applications, it is crucial to understand the mechanistic processes that determine drug release from PLGA-based formulations. In the current study, we developed a mechanistic model for the in vitro drug release of PLGA-based solid implants. The model accounts for all known critical quality attributes (CQAs) and considers the most important release rate processes, including water or dissolution medium influx into the porous structure of the implant, initial noncatalytic hydrolysis of PLGA, autocatalytic hydrolysis, dissolution of oligomers and monomers into the aqueous medium, the liberation of the trapped solid drug from the polymer matrix, dissolution of the solid drug into the wetted pore network, diffusion of the dissolved drug out of the implant, and distribution of the dissolved drug into the dissolution medium. The model has been validated using in vitro release data obtained from implants of four drugs (buserelin, afamelanotide, brimonidine, and nafarelin). The model presented in this manuscript provides valuable insights into the kinetics and mechanism of drug release from PLGA-based solid implants and has demonstrated the potential for optimizing formulation design. The in vitro release model, coupled with physiologically based pharmacokinetic (PBPK) modeling, can predict the in vivo performance of implants and can be used to support bioequivalence studies in a drug development program.

Preparation of ternary hybridized chitosan microspheres with photothermal effect for pH-sensitive long-lasting controlled release system and its release mechanism

To enhance the effective utilization of drugs and diminish the number of medications for patients, it is vital to investigate controlled long-acting drug release systems and their release mechanisms. In this study, chitosan microspheres were synthesized by cross-linking pH-sensitive Schiff bases, and Zif-8, a pH-sensitive component, was encapsulated within them. Furthermore, MXene was incorporated as a third component to augment the strength and photothermal synergistic characteristics of the microspheres. By adjusting the ratio of each component, the optimal ternary heterogeneous functional pH-controllable long-lasting drug release system was obtained. The optimal coating and the most effective adsorption-release effect were achieved. The release mechanism was examined under varying pH and temperature conditions. The release process was found to be divided into three stages. The initial phase was predominantly governed by the Fick diffusion mechanism, whereas the subsequent phases were primarily regulated by the pH-induced co-decomposition of CS and Zif-8, and the individual decomposition of CS, respectively.The drug was observed to be released in a linear manner during the latter two stages of the experiment. This was evidenced by the persistent release of ciprofloxacin hydrochloride in response to pH changes, and further supported by the results of tests on its antimicrobial properties. The drug release persisted for over three days at pH 5.4 and could be utilized repeatedly, exhibiting promising applications in drug delivery. Moreover, the drug's photothermal properties offer the possibility of developing synergistic therapeutic programs.

Review of Gold Nanoparticles: Synthesis, Properties, Shapes, Cellular Uptake, Targeting, Release Mechanisms and Applications in Drug Delivery and Therapy

The remarkable versatility of gold nanoparticles (AuNPs) makes them innovative agents across various fields, including drug delivery, biosensing, catalysis, bioimaging, and vaccine development. This paper provides a detailed review of the important role of AuNPs in drug delivery and therapeutics. We begin by exploring traditional drug delivery systems (DDS), highlighting the role of nanoparticles in revolutionizing drug delivery techniques. We then describe the unique and intriguing properties of AuNPs that make them exceptional for drug delivery. Their shapes, functionalization, drug-loading bonds, targeting mechanisms, release mechanisms, therapeutic effects, and cellular uptake methods are discussed, along with relevant examples from the literature. Lastly, we present the drug delivery applications of AuNPs across various medical domains, including cancer, cardiovascular diseases, ocular diseases, and diabetes, with a focus on in vitro and in vivo cancer research.

Point-Spread Function Deformations Unlock 3D Localization Microscopy on Spherical Nanoparticles.

Nanoparticles (NPs) have proven their applicability in biosensing, drug delivery, and photothermal therapy, but their performance depends critically on the distribution and number of functional groups on their surface. When studying surface functionalization using super-resolution microscopy, the NP modifies the fluorophore's point-spread function (PSF). This leads to systematic mislocalizations in conventional analyses employing Gaussian PSFs. Here, we address this shortcoming by deriving the analytical PSF model for a fluorophore near a spherical NP. Its calculation is four orders of magnitude faster than numerical approaches and thus feasible for direct use in localization algorithms. We fit this model to individual 2D images from DNA-PAINT experiments on DNA-coated gold NPs and demonstrate extraction of the 3D positions of functional groups with <5 nm precision, revealing inhomogeneous surface coverage. Our method is exact, fast, accessible, and poised to become the standard in super-resolution imaging of NPs for biosensing and drug delivery applications.

Synthesis, Urease Inhibition, Molecular Docking, and Optical Analysis of a Symmetrical Schiff Base and Its Selected Metal Complexes.

Designing and developing small organic molecules for use as urease inhibitors is challenging due to the need for ecosystem sustainability and the requirement to prevent health risks related to the human stomach and urinary tract. Moreover, imaging analysis is widely utilized for tracking infections in intracellular and in vivo systems, which requires drug molecules with emissive potential, specifically in the low-energy region. This study comprises the synthesis of a Schiff base ligand and its selected transition metals to evaluate their UV/fluorescence properties, inhibitory activity against urease, and molecular docking. Screening of the symmetrical cage-like ligand and its metal complexes with various eco-friendly transition metals revealed significant urease inhibition potential. The IC50 value of the ligand for urease inhibition was 21.80 ± 1.88 µM, comparable to that of thiourea. Notably, upon coordination with transition metals, the ligand-nickel and ligand-copper complexes exhibited even greater potency than the reference compound, with IC50 values of 11.8 ± 1.14 and 9.31 ± 1.31 µM, respectively. The ligand-cobalt complex exhibited an enzyme inhibitory potential comparable with thiourea, while the zinc and iron complexes demonstrated the least activity, which might be due to weaker interactions with the investigated protein. Meanwhile, all the metal complexes demonstrated a pronounced optical response, which could be utilized for fluorescence-guided targeted drug delivery applications in the future. Molecular docking analysis and IC50 values from in vitro urease inhibition screening showed a trend of increasing activity from compounds 7d to 7c to 7b. Enzyme kinetics studies using the Lineweaver-Burk plot indicated mixed-type inhibition against 7c and non-competitive inhibition against 7d.