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The utilization of three-dimensional (3D) printing technology is prevalent in the fabrication of oral sustained release preparations; however, there is a lack of research on 3D-printed osmotic pump tablets. A 3D-printed core-shell structure bezafibrate osmotic pump tablet was developed based on the characteristics of rapid absorption and short half-life of bezafibrate, utilizing semisolid extrusion (SSE) 3D printing technology. First, the properties of different shell materials were investigated to define the composition of the shell, and ultimately, the optimal formulation was found to be ethyl cellulose:cellulose acetate:polyethylene glycol = 2:1:2. The formulation of the tablet core was defined based on the printing performance and release behavior. The formulation consisted of bezafibrate, lactis anhydrous, sodium bicarbonate, sodium alginate, polyethylene oxide and sodium dodecyl sulfate at a ratio of 400:400:300:80:50:50. The tablet was capable of achieving zero-order release. The physicochemical properties were also characterized. The pharmacokinetic data analysis indicated that there were no statistically significant differences in the pharmacokinetic parameters between the 3D-printed tablets and the reference listed drugs. There was a strong correlation between the in vitro and in vivo results for the 3D-printed tablets. The results showed that SSE printing is a practical approach for manufacturing osmotic pump tablets.

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Hydrogels can serve as local drug delivery depots that protect the biological activity of labile therapeutics. However, drug release from conventional hydrogels is typically rapid, which is not ideal for many therapeutic agents. We developed a composite hydrogel that enables sustained drug release in response to ultrasound. The composite, termed an acoustically responsive scaffold (ARS), consists of a fibrin hydrogel and a phase-shift emulsion. Upon exposure to ultrasound, the emulsion is vaporized into bubbles, which leads to release of drugs contained within the emulsion. Previously, ARSs have been used in regenerative applications to stimulate blood vessel growth. Here, we characterize the release kinetics and mechanisms of ARSs. Release exhibits a triphasic pattern compromising a slow phase prior to ultrasound exposure; a transient, fast phase immediately after ultrasound exposure that follows a sigmoidal profile; and a sustained, steady phase. In each phase, we demonstrate how derived kinetics parameters are impacted by the ARS composition (e.g., fibrin and emulsion concentrations) and ultrasound properties (e.g., acoustic pressure, pulse duration). Using confocal microscopy, protein assays, and B-mode ultrasound imaging, we demonstrate that drug release from an ARS is independent of fibrin degradation and dependent on bubble growth. These results are critical in optimizing ARSs for delivery of therapeutic agents.

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The first step in comprehending the properties of Au10 clusters is understanding the lowest energy structure at low and high temperatures. Functional materials operate at finite temperatures; however, energy computations employing density functional theory (DFT) methodology are typically carried out at zero temperature, leaving many properties unexplored. This study explored the potential and free energy surface of the neutral Au10 nanocluster at a finite temperature, employing a genetic algorithm coupled with DFT and nanothermodynamics. Furthermore, we computed the thermal population and infrared Boltzmann spectrum at a finite temperature and compared it with the validated experimental data. Moreover, we performed the chemical bonding analysis using the quantum theory of atoms in molecules (QTAIM) approach and the adaptive natural density partitioning method (AdNDP) to shed light on the bonding of Au atoms in the low-energy structures. In the calculations, we take into consideration the relativistic effects through the zero-order regular approximation (ZORA), the dispersion through Grimme's dispersion with Becke-Johnson damping (D3BJ), and we employed nanothermodynamics to consider temperature contributions. Small Au clusters prefer the planar shape, and the transition from 2D to 3D could take place at atomic clusters consisting of ten atoms, which could be affected by temperature, relativistic effects, and dispersion. We analyzed the energetic ordering of structures calculated using DFT with ZORA and single-point energy calculation employing the DLPNO-CCSD(T) methodology. Our findings indicate that the planar lowest energy structure computed with DFT is not the lowest energy structure computed at the DLPN0-CCSD(T) level of theory. The computed thermal population indicates that the 2D elongated hexagon configuration strongly dominates at a temperature range of 50-800 K. Based on the thermal population, at a temperature of 100 K, the computed IR Boltzmann spectrum agrees with the experimental IR spectrum. The chemical bonding analysis on the lowest energy structure indicates that the cluster bond is due only to the electrons of the 6 s orbital, and the Au d orbitals do not participate in the bonding of this system.

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The photodegradation of azithromycin present was carried out in water using H2O2 under UV irradiation. The reaction variables considered in this study were the amount of H2O2 solution and the initial concentration of azithromycin to evaluate the performance of the photodegradation process. The azithromycin degradation was not observed in the dark during stirring for 20 min. The study showed an efficient photodegradation of azithromycin using H2O2 as an oxidant in the presence of UV irradiation. The azithromycin degradation was altered significantly by the pH of the irradiated solution. The degradation was low at an acidic pH and showed an increasing trend as the pH changed to basic. The azithromycin degradation increased with a higher amount (higher concentration) of H2O2. The degradation of azithromycin decreased with a higher concentration of azithromycin in the reacting solution. The highest degradation of AZT was achieved in 1 h using a 1.0 ppm AZT solution containing 3 mL of H2O2. The experimental data obtained were well-fitted to zero-order reaction kinetics. The results of this study were found quite excellent. They showed 100% degradation in 1 h when compared with those reported in the literature, both with photocatalysis using nanomaterials and photolysis using light irradiation and/or H2O2. The UV/H2O2 system was found to be quite efficient for the photodegradation of azithromycin, and this system can be applied to degrade other organic pollutants present in industrial wastewater.

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This study focuses on the combination of three-dimensional printing (3DP) and amorphous solid dispersion (ASD) technologies for the manufacturing of gastroretentive floating tablets. Employing hot melt extrusion (HME) and fused deposition modeling (FDM), the study investigates the development of drug-loaded filaments and 3D printed (3DP) tablets containing felodipine as model drug and hydroxypropyl methylcellulose (HPMC) as the polymeric carrier. Prior to fabrication, solubility parameter estimation and molecular dynamics simulations were applied to predict drug-polymer interactions, which are crucial for ASD formation. Physical bulk and surface characterization complemented the quality control of both drug-loaded filaments and 3DP tablets. The analysis confirmed a successful amorphous dispersion of felodipine within the polymeric matrix. Furthermore, the low infill percentage and enclosed design of the 3DP tablet allowed for obtaining low-density systems. This structure resulted in buoyancy during the entire drug release process until a complete dissolution of the 3DP tablets (more than 8 h) was attained. The particular design made it possible for a single polymer to achieve a zero-order controlled release of the drug, which is considered the ideal kinetics for a gastroretentive system. Accordingly, this study can be seen as an advancement in ASD formulation for 3DP technology within pharmaceutics.

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This research is dedicated to exploring the dynamics of milling chatter stability in orthopedic surgery robots, focusing on the impact of position modal parameters on chatter stability. Initially, we develop a dynamic milling force model for the robotic milling process that integrates both modal coupling and regenerative effects. We then employ the zero-order frequency domain method to derive a chatter stability domain model, visually represented through stability lobe diagrams (SLDs). Through conducting hammer test experiments, we ascertain the robot's modal parameters at varying positions, enabling the precise generation of SLDs. This study also includes experimental validation of the chatter SLD analysis method, laying the groundwork for further examination of chatter stability across different positional modal parameters. Finally, our analysis of the variations in modal parameters on the stability of robot milling chatter yields a theoretical framework for optimizing cutting parameters and developing control strategies within the context of orthopedic surgery robots.

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The purpose of this study was to conduct the kinetic assessment of iontophoretic delivery of niosomal tetracycline-HCl formulated in an electroconductive gel. Tween-80 and Span-80 were used to obtain tetracycline-HCl niosomes with an average diameter of 101.9 ± 3.3 nm, a polydispersity index of 0.247 ± 0.004, a zeta potential of - 34.1 mV, and an entrapment efficiency of 70.08 ± 0.16%. Four different gel preparations, two of which contained niosomal tetracycline-HCl, were transdermally delivered using Franz diffusion cells under the trigger effect of iontophoresis, applied at 0.2, 0.5, and 1 mA/cm2 current density. The control group was the passive diffusion results of the preparation made using a tetracycline-HCl-based drug marketed in Turkey. The control group was compared with the groups that contained (a) tetracycline-HCl in an electroconductive gel, (b) the niosomal tetracycline-HCl formulation in water, and (c) the niosomal tetracycline-HCl formulation in the electroconductive gel. The group with the niosomal formulation in the electroconductive gel displayed the highest increase in iontophoretic transdermal delivery relative to the control group, displaying a 2-, 2.1-, and 2.2-fold increase, respectively, by current density. The experimental results of transdermal delivery using the synergistic effect of niosomal formulation in electroconductive gel and the trigger effect of iontophoresis appeared to divert slightly from zero-order kinetics, demonstrating a statistically significant increase in the rate of controlled transdermal drug delivery. Considering that about 20% of the formulation is transdermally delivered in the first half-hour, the iontophoretic transdermal delivery of niosomal tetracycline-HCl can be efficiently used in local iontophoretic therapy.

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Transdermal drug delivery system (TDDS) was an effective way to realize controlled drug delivery. However, realizing zero-order controlled drug skin delivery was still challenging in the drug-in-adhesive patch. This study provided a strategy to accomplish this delivery form by stabilizing the drug concentration in adhesive through concentration-dependent competitive interaction. Clonidine (CLO) and Granisetron (GRA) were chosen as the model drugs which were of high skin permeability, and polydimethylaminoethyl acrylate (EA) as an excipient to interact with hydroxyphenyl adhesive (HP). Drug release, permeation and pharmacokinetic study were conducted to evaluate the controlled effect of HP-EA. The molecular interaction was characterized by FT-IR, 1H NMR and XPS. Dynamic simulation and molecular docking further clarified the competitive interaction involved in the release process. Both the drug skin permeation study of CLO and GRA patch based on the HP-EA adhesive showed good zero-order fitting with r of 0.994 and 0.998, compared with non-functional adhesive (0-PSA). Furthermore, the pharmacokinetic study of the CLO patch showed a plateau phase for around 52 h without influencing the area under concentration-time curve (AUC), indicating that the HP-EA could realize zero-order drug skin delivery. The mechanism study revealed that EA serving as a 'buffer component' promoted the conversion of the ionic CLO to the neutrals the as the neutrals released, which stabilized '1% neutrals CLO concentration'. In conclusion, the drug delivery system based on the concentration-dependent competitive interaction broadened our understanding of the molecular mechanisms involved in zero-order controlled release in transdermal patches which would promote the development of zero-order drug delivery in TDDS.

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It is conventionally expected that the performance of existing gas sensors may degrade in the field compared to laboratory conditions because (i) a sensor may lose its accuracy in the presence of chemical interferences and (ii) variations of ambient conditions over time may induce sensor-response fluctuations (i.e., drift). Breaking this status quo in poor sensor performance requires understanding the origins of design principles of existing sensors and bringing new principles to sensor designs. Existing gas sensors are single-output (e.g., resistance, electrical current, light intensity, etc.) sensors, also known as zero-order sensors (Karl Booksh and Bruce R. Kowalski, Analytical Chemistry, DOI: 10.1021/ac00087a718). Any zero-order sensor is undesirably affected by variable chemical background and sensor drift that cannot be distinguished from the response to an analyte. To address these limitations, we are developing multivariable gas sensors with independent responses, which are first-order analytical instruments. Here, we demonstrate self-correction against drift in two types of first-order gas sensors that operate in different portions of the electromagnetic spectrum. Our radiofrequency sensors utilize dielectric excitation of semiconducting metal oxide materials on the shoulder of their dielectric relaxation peak and achieve self-correction of the baseline drift by operation at several frequencies. Our photonic sensors utilize nanostructured sensing materials inspired by Morpho butterflies and achieve self-correction of the baseline drift by operation at several wavelengths. These principles of self-correction for drift effects in first-order sensors open opportunities for diverse emerging monitoring applications that cannot afford frequent periodic maintenance that is typical of traditional analytical instruments.

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The sonochemical oxidation activity was investigated for gas saturation and gas sparging under various liquid levels and volumes in 300 kHz sonoreactors. The liquid levels and volumes ranged from 5λ (25 mm, 0.47 L) to 50λ (250 mm, 4.30 L) and two gas mixtures, Ar:O2 (75:25) and N2:O2 (75:25), were used. Two types of reaction kinetics were observed to quantitatively analyze the sonochemical oxidation reactions: zero-order (KI dosimetry: C0 = 60.2 mM) and first-order (Bisphenol A (BPA) degradation: C0 = 0.043 mM). The masses of the sonochemical oxidation reactions were calculated and compared rather than the concentrations to more accurately compare the sonochemical oxidation activity under different liquid volume conditions. First, as the liquid level or volume increased for the zero-order reactions, the concentration of I3- ions representing the volume-averaged activity decreased substantially for gas saturation owing to the increase in liquid volume. However, gas sparging substantially enhanced sonochemical oxidation activity, and the mass of I3- ions representing the total activity remained constant as the liquid level increased from 20λ because of the improved liquid mixing and a shift in the sonochemical active zone. Second, as evidenced by the zero-order reactions, the concentration of BPA decreased considerably as the liquid level or volume increased in the first-order reactions. When gas sparging was used, higher reaction constants were obtained for both gas mixtures, ranging from 40λ to 50λ. However, a comparison of the sonochemical oxidation activity in terms of the degraded mass of BPA was inapplicable as the concentration of BPA decreased substantially and a lack of reactants occurred for the lower liquid level and volume conditions as the irradiation time elapsed. Instead, using the first-order reaction constant, a comparison of the required reaction times for a specific removal efficiency (30%, 60%, and 90%) was proposed. Gas sparging can substantially reduce the reaction time required for a liquid level of 40λ or higher.

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We propose that quantitative urine drug concentrations from LC-MS/MS measurements can be used to estimate zero and first order pharmacokinetics of the drugs oxycodone, hydrocodone, buprenorphine, methadone, and fentanyl. We observed the ratio of metabolite to parent drug could be used for this estimate. As the amount of observed parent drug increased, the metabolic ratio decreased, indicating a shift from first order to zero order metabolism. After making assumptions of bioavailability, percent of drug excreted into urine, we developed estimates of the saturating dosages for these drugs.

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As basic optical elements, waveplates with anisotropic electromagnetic responses are imperative for manipulating light polarization. Conventional waveplates are manufactured from bulk crystals (e.g., quartz and calcite) through a series of precision cutting and grinding steps, which typically result in large size, low yield, and high cost. In this study, a bottom-up method is used to grow ferrocene crystals with large anisotropy to demonstrate self-assembled ultrathin true zero-order waveplates without additional machining processing, which is particularly suited for nanophotonic integration. The van der Waals ferrocene crystals exhibit high birefringence (Δn (experiment) = 0.149  ±  0.002 at 636 nm), low dichroism Δκ (experiment) = -0.0007 at 636 nm), and a potentially broad operating range (550 nm to 20 µm) as suggested by Density Functional Theory (DFT) calculations. In addition, the grown waveplate's highest and the lowest principal axes (n1 and n3 , respectively) are in the a-c plane, where the fast axis is along one natural edge of the ferrocene crystal, rendering them readily usable. The as-grown, wavelength-scale-thick waveplate allows the development of further miniaturized systems via tandem integration.

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Colon-targeted drug delivery is gradually attracting attention because it can effectively treat colon diseases. Furthermore, electrospun fibers have great potential application value in the field of drug delivery because of their unique external shape and internal structure. In this study, a core layer of hydrophilic polyethylene oxide (PEO) and the anti-colon-cancer drug curcumin (CUR), a middle layer of ethanol, and a sheath layer of the natural pH-sensitive biomaterial shellac were used in a modified triaxial electrospinning process to prepare beads-on-the-string (BOTS) microfibers. A series of characterizations were carried out on the obtained fibers to verify the process-shape/structure-application relationship. The results of scanning electron microscopy and transmission electron microscopy indicated a BOTS shape and core-sheath structure. X-ray diffraction results indicated that the drug in the fibers was in an amorphous form. Infrared spectroscopy revealed the good compatibility of the components in the fibers. In vitro drug release revealed that the BOTS microfibers provide colon-targeted drug delivery and zero-order drug release. Compared to linear cylindrical microfibers, the obtained BOTS microfibers can prevent the leakage of drugs in simulated gastric fluid, and they provide zero-order release in simulated intestinal fluid because the beads in BOTS microfibers can act as drug reservoirs.

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Dihydromyricetin (DHM) is an important natural flavonoid. However, most of DHM preparations have shown shortcomings such as low drug loading, poor drug stability, and/or large fluctuations in blood concentration. This study aimed to develop a gastric floating tablet with a double-layered structure for zero-order controlled release of DHM (DHM@GF-DLT). The final product DHM@GF-DLT showed a high average cumulative drug release at 24 h that best fit the zero-order model, and had a good floating ability in the stomach of the rabbit with a gastric retention time of over 24 h. The FTIR, DSC, and XRPD analyses indicated the good compatibility among the drug and the excipients in DHM@GF-DLT. The pharmacokinetic study revealed that DHM@GF-DLT could prolong the retention time of DHM, reduce the fluctuation of blood drug concentration, and enhance the bioavailability of DHM. The pharmacodynamic studies demonstrated that DHM@GF-DLT had a potent and long-term therapeutic effect on systemic inflammation in rabbits. Therefore, DHM@GF-DLT had the potential to serve as a promising anti-inflammatory agent and may develop into a once-a-day preparation, which was favorable to maintain a steady blood drug concentration and a long-term drug efficacy. Our research provided a promising development strategy for DHM and other natural products with a similar structure to DHM for improving their bioavailability and therapeutic effect.

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In the present study, a comprehensive polymer degradation-drug diffusion model is developed to describe the polymer degradation kinetics and quantify the release rate of an active pharmaceutical ingredient (API) from a size-distributed population of drug-loaded poly(lactic-co-glycolic) acid (PLGA) carriers in terms of material and morphological properties of the drug carriers. To take into account the spatial-temporal variation of the drug and water diffusion coefficients, three new correlations are developed in terms of spatial-temporal variation of the molecular weight of the degrading polymer chains. The first one relates the diffusion coefficients with the time-spatial variation of the molecular weight of PLGA and initial drug loading and, the second one with the initial particle size, and the third one with evolution of the particle porosity due to polymer degradation. The derived model, comprising a system of partial differential and algebraic equations, is numerically solved using the method of lines and validated against published experimental data on the drug release rate from a size distributed population of piroxicam-PLGA microspheres. Finally, a multi-parametric optimization problem is formulated to calculate the optimal particle size and drug loading distributions of drug-loaded PLGA carriers to realize a desired zero-order drug release rate of a therapeutic drug over a specified administration period of several weeks. It is envisaged that the proposed model-based optimization approach will aid the optimal design of new controlled drug delivery systems and, consequently, the therapeutic outcome of an administered drug.

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Simple, direct, rapid, and sensitive HPLC and spectrophotometric methods were established for simultaneous estimation of a novel combination of budesonide and azelastine (BUD/AZL) in their laboratory-prepared mixture and dosage form according to the medicinally recommended ratio 1:4.28. Budesonide is an important inhalation corticosteroid that plays a vital role in the inhibition of COVID-19 replication and cytokine production. The first chromatographic method was created for the simultaneous estimation of BUD epimers in the presence of AZL with excellent efficiency in a relatively short chromatographic run (< 9 min). The separation of BUD epimers with AZL was carried out on a C18 column using acetonitrile: phosphate buffer of pH 3.5 adjusted by 0.2 M orthophosphoric acid (40:60, v/v) as a mobile phase, UV detection at 230 nm and a flow rate of regulated at 2 mL/min. Besides, three spectrophotometric methods were applied for the simultaneous determination of the provided mixture adopting zero order, first order derivative, and ratio first derivative approaches. The Zero-order spectrophotometry was used for the determination of AZL in presence of BUD, where BUD shows no absorbance at 290 nm. The first derivative amplitude at 265 nm (1D265) (zero-crossing of AZL) and the ratio of first derivative amplitudes at 270 nm (1DD270) using 10.0 µg mL-1 AZL as divisor was chosen for the simultaneous determination of BUD in the presence of AZL in the binary mixture. The proposed methods were found to be rectilinear in the concentration range of (0.4-40.0 µg mL-1) and (0.05-40.0 µg mL-1) for BUD and AZL, respectively in the HPLC method. Whereas the concentration range for AZL in the zero-order method was (1.0-35.0 µg mL-1) and for BUD in the first derivative and ratio derivative method was (6.0-20.0 µg mL-1). Validation of the suggested approaches according to the ICH criteria was performed. Furthermore, to ensure the proposed approaches' greenness, The AGREE and GAPI metrics were utilized, and the afforded results revealed an excellent greenness of the proposed approaches.

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The electrocardiogram (ECG) is the standard method in clinical practice to non-invasively analyze the electrical activity of the heart, from electrodes placed on the body's surface. The ECG can provide a cardiologist with relevant information to assess the condition of the heart and the possible presence of cardiac pathology. Nonetheless, the global view of the heart's electrical activity given by the ECG cannot provide fully detailed and localized information about abnormal electrical propagation patterns and corresponding substrates on the surface of the heart. Electrocardiographic imaging, also known as the inverse problem in electrocardiography, tries to overcome these limitations by non-invasively reconstructing the heart surface potentials, starting from the corresponding body surface potentials, and the geometry of the torso and the heart. This problem is ill-posed, and regularization techniques are needed to achieve a stable and accurate solution. The standard approach is to use zero-order Tikhonov regularization and the L-curve approach to choose the optimal value for the regularization parameter. However, different methods have been proposed for computing the optimal value of the regularization parameter. Moreover, regardless of the estimation method used, this may still lead to over-regularization or under-regularization. In order to gain a better understanding of the effects of the choice of regularization parameter value, in this study, we first focused on the regularization parameter itself, and investigated its influence on the accuracy of the reconstruction of heart surface potentials, by assessing the reconstruction accuracy with high-precision simultaneous heart and torso recordings from four dogs. For this, we analyzed a sufficiently large range of parameter values. Secondly, we evaluated the performance of five different methods for the estimation of the regularization parameter, also in view of the results of the first analysis. Thirdly, we investigated the effect of using a fixed value of the regularization parameter across all reconstructed beats. Accuracy was measured in terms of the quality of reconstruction of the heart surface potentials and estimation of the activation and recovery times, when compared with ground truth recordings from the experimental dog data. Results show that values of the regularization parameter in the range (0.01-0.03) provide the best accuracy, and that the three best-performing estimation methods (L-Curve, Zero-Crossing, and CRESO) give values in this range. Moreover, a fixed value of the regularization parameter could achieve very similar performance to the beat-specific parameter values calculated by the different estimation methods. These findings are relevant as they suggest that regularization parameter estimation methods may provide the accurate reconstruction of heart surface potentials only for specific ranges of regularization parameter values, and that using a fixed value of the regularization parameter may represent a valid alternative, especially when computational efficiency or consistency across time is required.

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Microparticles are successfully engineered through controlled interfacial self-assembly of polymers to harmonize ultrahigh drug loading with zero-order release of protein payloads. To address their poor miscibility with carrier materials, protein molecules are transformed into nanoparticles, whose surfaces are covered with polymer molecules. This polymer layer hinders the transfer of cargo nanoparticles from oil to water, achieving superior encapsulation efficiency (up to 99.9%). To control payload release, the polymer density at the oil-water interface is enhanced, forming a compact shell for microparticles. The resultant microparticles can harvest up to 49.9% mass fraction of proteins with zero-order release kinetics in vivo, enabling an efficient glycemic control in type 1 diabetes. Moreover, the precise control of engineering process offered through continuous flow results in high batch-to-batch reproducibility and, ultimately, excellent scale-up feasibility.

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Diarylheptanoids (DAs) characterized by a 1,7-diphenylheptane structural skeleton are considered a novel class of phytoestrogens. The DAs available in Curcuma comosa Roxb. (C. comosa) extract demonstrated significant estrogenic activities both in vitro and in vivo. This study aimed to develop and comprehensively evaluate a mucoadhesive vaginal gel for the sustained release of DAs. Different mucoadhesive polymers as gelling agents were investigated. C. comosa ethanolic crude extract was used as a source of DAs. All C. comosa gels were light brown homogeneous with pH within 4.4-4.6. Their flow behaviors were pseudoplastic with a flow behavior index of 0.18-0.38. The viscosity at a low shear rate varied from 6.2 to 335.4 Pa·s. Their mechanical and extrudability properties were associated well with rheological properties. Polycarbophil (PCP):hydroxypropyl methylcellulose (HPMC) blends had a higher mucoadhesiveness to porcine vaginal mucosa than those of PCP-based or HPMC-based gels. All C. comosa gels exhibited a sustained, zero-order DA release pattern over 72 h. Korsmeyer and Peppas equation fitting indicated a non-Fickian, case II transport release mechanism. C. comosa gels had good physical and chemical stability under low-temperature storage for up to 12 months. PCP:HPMC-based mucoadhesive gels could be a proper delivery system for vaginal administration of DAs.

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Hybrid nanomaterials possess integrated multi-components to syncretize various properties and functions within a single entity. Owing to this synergistic effect, they promise efficient anti-cancer therapy. In line with this target, we produced stimuli-responsive nanoparticle-nanofiber hybrids (NNHs) via embedding photoresponsive natural melanin nanoparticles (MNPs) within a biocompatible polycaprolactone (PCL) nanofiber matrix. Electrospinning was performed to produce monolithic and core-shell structured NNHs using a single and a coaxial nozzle. The NNHs were upgraded to drug delivery systems by model hydrophilic drug-ampicillin (amp)-loading. The drug release results showed that monolithic PCL meshes displayed a burst release, whereas nanohybrid formation with MNPs improved the release profile toward Fickian diffusion. Core-shell NNH presented a more sustained drug release profile than its MNP-free replica and monolithic NNH because its encapsulating shell layer hindered the diffusion of the drug. The photodynamic therapy accompanied by UV-A-irradiation on monolithic and core-shell NNHs yielded up to 34 % and 37 % malignant melanoma cell death. Moreover, this study proved the potency of MNPs-enhanced NNHs in drug delivery and photodynamic therapy applications. Even so, more efforts should be concerted to unlock unknown features of the NNHs, which have the power to advance emerging areas, including but not limited to material science, biosensing, and theranostics.

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