Drug Release Profile Research Articles

Preparation and Characterization of Ozonated Liposomes Loaded with Curcumin: A Potential Approach for Diabetic Retinopathy Treatment

Background: Limitations in drug penetration are overcome by nanotechnology, particularly liposomes, which enhance targeted administration of ocular medications. Liposomes can augment the therapeutic effects of curcumin, a natural compound with positive impacts on the retina. Treatments for eye diseases can also benefit from the antibacterial properties of ozonated oil liposomes. Objectives: This study aims to develop and evaluate ozonated liposomes loaded with curcumin for ocular drug delivery applications, specifically targeting diabetic retinopathy (DR). Methods: Liposomal nanoparticles were prepared using thin-film hydration, incorporating phospholipids, lecithin, cholesterol, ozonated oil, and curcumin. We assessed physicochemical properties including particle size, zeta potential, encapsulation efficiency (EE), and morphology. Drug release profiles and stability studies were also conducted. Results: The optimized liposomes showed a particle size of 84.77 nm, a zeta potential of -16.8 mV, and an EE of 94.73%. The formulation exhibited sustained curcumin release over 24 hours, reaching 82.09% cumulative release. Stability studies indicated minimal changes in key parameters over three months at room temperature. Conclusions: The developed ozonated liposomal formulation demonstrates promising characteristics for curcumin delivery, potentially enhancing its therapeutic efficacy in ocular applications, particularly for DR.

Surface-functionalized UIO-66-NH2 for dual-drug delivery of vancomycin and amikacin against vancomycin-resistant Staphylococcus aureus

BackgroundConventional antibacterial compounds can inhibit the growth of microorganisms, but their adverse effects and the development of drug limit their widespread use. The current study aimed to synthesize PEG-coated UIO-66-NH2 nanoparticles loaded with vancomycin and amikacin (VAN/AMK-UIO-66-NH2@PEG) and evaluate their antibacterial and anti-biofilm activities against vancomycin-resistant Staphylococcus aureus (VRSA) clinical isolates.MethodsThe VAN/AMK-UIO-66-NH2@PEG were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), and dynamic light scattering (DLS) to determine their size, polydispersity index (PDI), encapsulation efficiency (EE%), zeta-potential, drug release profile, and physical stability. Antibacterial activity was evaluated using minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and time-kill assays. Biofilm formation by VRSA was assessed using the crystal violet (CV) and minimum biofilm eradication concentration (MBEC) assays. The effect of sub-MIC concentrations of the formulations on the expression of biofilm-related genes (icaA, icaD) and resistance-related genes (mecA, vanA) was investigated using quantitative real-time polymerase chain reaction (RT-qPCR).ResultsAs demonstrated by MIC, MBC and time-kill assay, the VAN/AMK-UIO-66-NH2@PEG nanoparticles exhibited enhanced antibacterial activity against VRSA isolates compared to free drugs and prepared formulations. Furthermore, CV and MBEC tests indicated that the VAN/AMK-UIO-66@NH2/PEG can reduce biofilm formation dramatically compared to VAN/AMK and VAN/AMK-UIO-66@NH2, due to its great drug release properties. This study also found that the expression level of the mecA, vanA, icaA, and icaD genes in VAN/AMK-UIO-66@NH2/PEG treated VRSA isolates was substantially decreased compared to other groups.ConclusionsThese findings highlighted the efficiency of VAN/AMK-UIO-66@NH2/PEG in combating antimicrobial resistance and biofilm formation in VRSA isolates. Future studies, particularly in vivo models, are necessary to evaluate the safety, efficacy, and clinical applicability of these nanoparticles for the treatment of bacterial infections.

A functional dual responsive CMC/OHA/SA/TOB hydrogel as wound dressing to enhance wound healing.

Within the clinical realm, the complexities of wound healing have consistently presented formidable challenges. Recent advancements, notably in hydrogel technologies, have broadened the therapeutic spectrum. This study focuses on investigating a novel dual responsive composite hydrogel for wound healing. This hydrogel is ingeniously designed to maintain an optimal moist environment, expedite healing, and combat bacterial infection during wound recovery. This study combining carboxymethyl chitosan (CMC), oxidized hyaluronic acid (OHA), and sodium alginate (SA), in addition, tobramycin (TOB) was incorporated to create a CMC/OHA/SA/TOB hydrogel. Hydrogel cross-linking was verified by infrared spectroscopy, and the microstructure was examined with scanning electron microscopy. We explored its swelling and degradation behaviors in different pH environments. The drug release profile and biocompatibility was evaluated via cytotoxicity and hemolysis assays. The antibacterial efficacy of hydrogel was tested in both solid and liquid media. Additionally, the wound models in Sprague-Dawley (SD) rat was employed to investigate the hydrogel's wound healing capabilities in vivo. Results showed that CMCOHA/SA/TOB hydrogel was effectively cross-linked with a network structure. The hydrogel exhibited pronounced responsiveness in its swelling and degradation characteristics, which was significantly influenced by different levels of pH. In vitro results demonstrated that the CMC/OHA/SA/TOB hydrogel exhibits limited cytotoxicity and hemolysis, coupled with a drug release profile of dual responsive characteristics. Antibacterial activity of the hydrogel against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli was confirmed. Furthermore, in vivo experiments underscored the hydrogel's proficiency in promoting wound healing, highlighting its potential for clinical applications. The CMC/OHA/SA/TOB hydrogel not only fosters a moist environment essential for wound healing and enhances structural stability, but it also exhibits functional dual responsive capabilities in swelling and degradation. These distinctive abilities enable the precise release of TOB, thereby optimizing wound healing.

Encapsulation of Rifampicin in Solid Lipid Nanoparticles by Microwave‐Assisted Microemulsion Method

AbstractRifampicin (RF) is a potent antibiotic, but its clinical effectiveness is limited by poor water solubility and stability. To overcome these limitations, RF is encapsulated in solid‐lipid nanoparticles (SLNs) using a one‐pot microwave microemulsion method. This study aimed to synthesize and characterize RF‐loaded SLNs, evaluating their physicochemical characteristics and antimicrobial efficacy. The synthesized SLNs exhibit particle sizes ranging from 150 to 200 nm, with a high encapsulation efficiency of ≈55% and high loading capacity. The particles are imaged by cryogenic‐transmission electron microscopy and found to be circular and elongated, with RF homogenously distributed throughout the particles. The RF‐loaded SLNs demonstrate potent antimicrobial activity, as evidenced by disc diffusion assays. The SLNs exhibits a sustained drug release profile, highlighting their potential as an effective drug delivery system for antimicrobial treatment. These findings suggest that SLNs can enhance the stability, bioavailability, and therapeutic efficacy of hydrophobic drugs like RF.

Ultrasound‐Responsive Lipid Nanoparticles for Targeted Therapy and Controlled Drug Release in Non‐Small Cell Lung Cancer

AbstractMultifunctional drug delivery systems offer tremendous potential for improving antitumor efficacy, precise drug targeting, and controlled drug release in treating non‐small cell lung cancer (NSCLC). In this study, the study develops a novel tumor‐targeting ultrasound‐responsive lipid nanoparticle (TUSL) platform capable of responding to external stimulation, enabling precise drug delivery with controlled release at the tumor site while minimizing systemic exposure and side effects. The TUSL platform is designed to carry doxorubicin (DOX) and tetrandrine (TET), specifically for drug‐resistant NSCLC. The developed TUSL exhibits a nano sized spherical structure with a hydrodynamic size of 141.8 nm, accommodating anti‐cancer drugs with loading capacities of 3.8% and 6.2% for TET and DOX, respectively. TUSL is engineered to target the epidermal growth factor receptor (EGFR) while demonstrating an ultrasound‐triggered drug release profile. Through the generation of CO2 bubbles upon ultrasound stimulation, the TUSL enhances DOX and TET internalization into tumor cells. In tumor‐bearing mice, TUSL administration demonstrates a superior tumor accumulation with minimal off‐target toxicity. The combined treatment with DOX and TET within TUSL exhibits synergistic effects, effectively inhibiting the growth of drug‐resistant NSCLC tumors. These findings highlight the efficacy of the EGFR‐targeted TUSL formulation in overcoming drug resistance and enhancing therapeutic outcomes in NSCLC.

A comparative analysis of PLA and PCL microparticles for hydrophilic and hydrophobic drugs.

This study aims to investigate Polylactic Acid (PLA) and Polycaprolactone (PCL) polymers for microencapsulation of hydrophilic and hydrophobic anti-glaucoma drugs using an emulsion-based solvent evaporation technique. Microparticle size was analysed using optical microscopy, while drug-polymer interactions through Dynamic-Light-Scattering (DLS) and Fourier-Transform-Infra-red/Attenuated-Total-Reflection spectroscopy (FTIR/ATR). In vitro, drug release studies were performed to investigate drug encapsulation and release profiles. Spherical microparticles, with particle size 94 ± 6.9 μm for PCL-based and 100 ± 3.74 μm for PLA-based formulation, were obtained. Drug release studies showed 100% release over about 32 days, with encapsulation efficiency (%EE) and drug loading (%w/w) reaching up to 95 and 2.84% for PLA-based and 97 and 2.91% for PCL-based microparticles, respectively. DLS studies reveal an increase in hydrodynamic radius (RH), which correlates to enhanced drug encapsulation. So, the nature of the drug and polymer significantly impacts drug encapsulation and release, with drug-polymer interactions playing a crucial role alongside experimental parameters.

PH-sensitive polymeric hydrogels coated with cobalt ferrite nanoparticles for combined drug delivery as controlled release carriers: fabrication and in-vitro estimation

In this investigation, we produced pH-responsive hydrogels for the controlled release of drugs by graft copolymerizing Gum ghatti and acrylic acid (AA) in an aqueous medium. N, N′-methylene-bis-acrylamide (MBA) and ammonium persulphate (APS) served as cross-linkers during the synthesis process. Our research explores the integration of cobalt ferrite (CoFe2O4) magnetic nanoparticles (CFMNPs) in delivering a combination drug comprising metformin hydrochloride and sodium diclofenac. The diverse applications of CoFe2O4 nanoparticles have driven the exploration of innovative and environmentally sustainable production methods. The development of novel materials for nanoparticle synthesis adheres to the principles of “Green Chemistry” through a co-precipitation technique. Characterization of the cross-linked hydrogels involved Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) analyses. In vitro drug release kinetics were observed under physiological conditions using Ultraviolet–Visible Spectroscopy. The drug-loaded Gg-cl-poly(AA)/CoFe2O4 hydrogels exhibited a sustained drug release profile over 24 h, with significant release occurring at a pH of 4. To comprehend the drug release mechanism, we employed kinetic modeling, encompassing Zero order, First order, Higuchi model, Hixson-Crowell model, and Korsmeyer-Peppas model, for all developed hydrogels. The findings indicated that the drug release mechanism from the hydrogels followed the Korsmeyer-Peppas model. The study concludes that the developed hydrogel offers a promising solution for the controlled administration of metformin hydrochloride and diclofenac sodium.Graphical

Application of biogenic silver nanoparticle incorporated nanofibers in biomedical science

The applications of nanotechnology are expanding into medical science for designing new medical devices related products. These products can deliver targeted therapies to diseases such as cancer and peripheral artery treatment. Therefore, with the goal to treat peripheral artery disease, we integrated biogenic silver nanoparticles (AgNPs) into polyethylene glycol-polycaprolactone (PEG-PCL) nanofibrous (NFs). The AgNPs-NFs mats were successfully fabricated using a blended electrospinning process. AgNPs with average sizes of 35–55 nm were produced and characterized using multiple techniques such as UV–Vis spectroscopy, TEM, SEM and FTIR. Nanofibrous membranes containing 1 %, 2 %, and 3 % AgNPs by weight were developed, showing a reduction in fiber diameter from 473 nm to 179 nm due to the introduction of charged particles. The scaffold’s suitability and drug release profile were critically analyzed, revealing results consistent with optimal biomedical applications. Preliminary studies indicated that AgNPs dose-dependent inhibition of human umbilical vein endothelial cells (HUVECs) may potentially help prevent atherosclerosis. These findings underscore the potential of AgNPs integrated PEG-PCL NFs mats for advanced biomedical applications.

Cubosomes hydrogel containing silver based organometallic compounds for enhanced wound healing of burns: In vitro and in vivo studies

The aim of this study is to investigate the treatment of burn wounds and bacterial infections, specifically focusing on silver(I) N-heterocyclic carbene (Ag-NHC) loaded into cubosomes. Ag-NHC is an organometallic complex of silver (Ag) and can be considered an active pharmaceutical ingredient for the topical treatment of burns. A novel nanoparticle system, cubosome dispersions, was formulated using high pressure homogenization methods with different concentrations of lipid phase glyceryl monooleate (GMO), surfactants such as poloxamer 407 (F-127), and polyvinyl alcohol (PVA). The optimized formulation (U6) was characterized by in vitro drug release profile (90.54 ± 1.17 %), particle size (126.7 ± 0.98 nm), zeta potential (−21.6 ± 6.83 mV), entrapment efficiency (89.30 ± 1.46 %), and morphology as observed by transmission electron microscopy (TEM). The U6 formulation was incorporated into a hydrogel containing Carbopol 940 to form a cubosomal hydrogel (cubogel). The cubogel was characterized by the in vitro release of Ag-NHC (92 %), entrapment efficiency (>90 %), pH (5.3), viscosity (1.2 cP), spreadability, and TEM. From the in vitro drug release pattern, it was concluded that the U6 formulation showed slow and sustained drug release over 24 h, and demonstrated superior burn healing compared to marketed products. The in vivo wound healing study revealed that the cubogel demonstrated a superior burn healing rate compared to commercially available products (Quench® and Clotrimazole®). The in vivo histopathological results showed that the prepared cubogel was effective in treating second-degree burns, with no side effects or skin irritation, compared to commercial products. Additionally, Ag-NHC-loaded cubogel facilitated sustained release for treating burn wounds without any bacterial infections. The current findings provide a strong basis for the initiating phase 0 clinal trials, highlighting significant potential for the further research to benefit the pharmaceutical industry.

Cetuximab scFv-Modified 5-FU Loaded Chitosan Nanoparticles: "A Novel Therapeutic Platform."

Colorectal cancer [CRC] is among the most fatal types of cancer. An active targeting delivery system that specifically interacts with CRC cells could improve the therapy's outcomes. Herein, Cetuximab single-chain fragment variable antibody [scFv] fragments were conjugated to the surface of 5-FU encapsulated chitosan nanoparticles [CS NPs] to develop an effective therapeutic platform [scFv-CS/5-FU NPs]. CS/5-FU NPs were synthesized using a special fluidic system. Encapsulation efficiency [EE], loading capacity [LC], and the drug release profile of the particles were determined. scFv fragments were produced recombinantly and tailored on the surface of CS/5-FU NPs. The physicochemical features of scFv-CS/5-FU NPs were also characterized. MTT and flow cytometry assay investigated the toxicity effect of scFv-CS/5-FU NPs on the HCT116 cell line. CS/5-FU NPs had a homogenous spherical shape. They possessed sustainable drugrelease behavior. The produced scFv-CS/5-FU NPs were also spherical. scFv-CS/5-FU NPs significantly decreased the viability of cancerous cells in a dose-dependent manner and induced apoptosis in 97.97% of targeted cells. scFv-CS/5-FU NPs showed remarkable anti-CRC activity. This novel targeting delivery system reduced the effective dose of 5-FU which is of vital importance to decrease the devastating side effects of chemotherapy.

Extrusion-Based Three-Dimensional Printing of Metronidazole Immediate Release Tablets: Impact of Processing Parameters and in Vitro Evaluation

PurposeThe current study assessed the potential of a pneumatic 3D printer in developing a taste-masked tablet in a single step. Metronidazole (MTZ) was chosen as the model drug, and Eudragit® E PO was used as a taste-masking polymer to produce taste-masked tablets.MethodsThe study focused on optimizing processing parameters, such as the nozzle's printing speed, the printhead's heating temperature, and the pressure. Oval-shaped tablets were printed with a rectilinear printing pattern of 30% and 100% infill and evaluated for in vitro drug release and taste masking. The 3D-printed tablets are also characterized using Differential Scanning Calorimetry (DSC), Fourier-transform Infrared Spectroscopy (FTIR), and Scanning Electron Microscopy (SEM).ResultsThe infill density impacts the drug release profile of the tablets. F9, F10, and F11 displayed desired printability among the formulations, with F9 and F10 exhibiting over 85% drug release within 60 min in the in vitro dissolution study. The F9 formulation, with 30% infill, effectively masked the bitter taste of MTZ in the in vitro dissolution study carried out in a pH 6.8 artificial salivary medium. The observed release was below the tasting threshold concentration of the model drug.ConclusionIn summary, 3-dimensional extrusion-based printing combines the effects of hot-melt extrusion and fused deposition modeling techniques in a single-step process, demonstrating potential as an alternative to the fused-deposition model 3D printing technique and warranting further exploration.Graphical

Oral mucoadhesive drug delivery system: Formulation strategies and evaluation techniques

Mucoadhesive drug delivery systems (MDDS) represent an innovative method for administering drugs through oral routes such as the buccal, sublingual, and gingival areas. These systems leverage natural or synthetic polymers to ensure prolonged adherence to mucosal surfaces, enabling extended and controlled release of medication. Several factors influence the effectiveness of mucoadhesion, including the hydrophilicity of polymers, molecular weight, and environmental factors like pH and moisture levels. MDDS can take various forms, including tablets, films, patches, lozenges, and gels, each offering different drug release profiles such as immediate, sustained, or controlled. These systems enhance drug bioavailability by avoiding first-pass metabolism, making them particularly beneficial for medications with low oral bioavailability or those requiring targeted delivery. Although MDDS offer improved patient compliance and therapeutic effectiveness, they still face challenges like irritation, taste concerns, and the diluting effect of saliva, which can impact drug stability. Despite these challenges, MDDS hold significant promise for advancing drug delivery technologies across various medical applications. This review thoroughly examines the mechanisms, advantages, limitations, and future prospects of mucoadhesive drug delivery systems.

Reimagining Anti-Inflammatory Drugs Delivery: The Integration of Ordered Mesoporous Silica and MOF Materials for Enhanced Therapeutic Outcomes

Abstract Migraine, one of the neurological conditions, affects approximately 15% of the global population. It is characterized by intense headaches accompanied by nausea, vomiting, and heightened sensitivity to light. The first line of drugs for treating migraine are non-steroidal anti-inflammatory drugs. Unfortunately, these medications suffer from poor solubility in water, uncontrolled release, and numerous adverse side effects. In order to maximize their therapeutic effect by preventing premature release and degradation, novel drug delivery systems based on composites are being dynamically developed. Herein, the biocompatible ketoprofen, naproxen sodium, and diclofenac sodium vehicles integrating ordered mesoporous silica (SBA-16) with Fe-based metal–organic frameworks (MIL-101(Fe)) were synthesized via the solvothermal method. The composites were characterized by different percentages of MIL-101(Fe) 
(25 and 50 wt.%), which had a significant impact on their porosity, structure, and number of functional groups. The SBA-16@MIL-101(Fe)-25 and SBA-16@MIL-101(Fe)-50 samples exhibited BET surface areas of 768 and 324 m2/g, respectively. Their sorption capacities towards selected anti-inflammatory drugs were in the range of 141-318 mg/g for ketoprofen, 481-490 mg/g for naproxen sodium, and 246-589 mg/g for diclofenac sodium, notably exceeding the values obtained for pure mesoporous silica (5-9 mg/g). Morphological defects and specific functional groups, derived from SBA-16 and MIL-101(Fe), contributed to generating new adsorption sites in composites, enhancing host-guest interactions. The drug release profiles were determined by the carrier porosity, surface charge, and the presence of functional groups. The diffusion of ketoprofen and diclofenac sodium from the composites into the phosphate buffer (pH 7.7), mimicking rectal fluid, occurred in a more controlled manner compared to pristine silica. The SBA-16@MIL-101(Fe)-50 carrier released 82% of ketoprofen and 90% of diclofenac sodium over 24 hours.

Impact of Carbon Source on Bacterial Cellulose Network Architecture and Prolonged Lidocaine Release

The biosynthesis of bacterial cellulose (BC) is significantly influenced by the type of carbon source available in the growth medium, which in turn dictates the material’s final properties. This study systematically investigates the effects of five carbon sources—raffinose (C18H32O16), sucrose (C12H22O11), glucose (C6H12O6), arabinose (C5H10O5), and glycerol (C3H8O3)—on BC production by Komagataeibacter hansenii. The varying molecular weights and structural characteristics of these carbon sources provide a framework for examining their influence on BC yield, fiber morphology, and network properties. BC production was monitored through daily measurements of optical density and pH levels in the fermentation media from day 1 to day 14, providing valuable insights into bacterial growth kinetics and cellulose synthesis rates. Scanning electron microscopy (SEM) was used to elucidate fibril diameter and pore size distribution. Wide-angle X-ray scattering (WAXS) provided a detailed assessment of crystallinity. Selected BC pellicles were further processed via freeze-drying to produce a foam-like material that maximally preserves the natural three-dimensional structure of BC, facilitating the incorporation and release of lidocaine hydrochloride (5%), a widely used local anesthetic. The lidocaine-loaded BC foams exhibited a sustained and controlled release profile over 14 days in simulated body fluid, highlighting the importance of the role of carbon source selection in shaping the BC network architecture and its impact on drug release profile. These results highlight the versatility and sustainability of BC as a platform for wound healing and drug delivery applications. The tunable properties of BC networks provide opportunities for optimizing therapeutic delivery and improving wound care outcomes, positioning BC as an effective material for enhanced wound management strategies.

Statistical Design and Analysis for Enhanced Production of Tetracycline‐Conjugated Copper Oxide Nanoparticles with Improved Antimicrobial Properties

AbstractPurpose: Since decades, numerous antibiotics have been used to treat different bacterial illnesses; among these, tetracycline is one of the commonly used antibiotics, which has led to development of bacterial resistance. To tackle this critical issue, we have developed a novel, biocompatible nanodrug that improves the antibacterial activity of tetracycline by conjugating it with copper oxide nanoparticles, thereby addressing the problem of multidrug resistance in bacteria. Methods: In this study, using unipot approach, tetracycline conjugated copper oxide nanoparticles were synthesized where tetracycline act as reducing as well as stabilizing agent. These nanoparticles were characterized by different analytical and microscopic technique. For statistical analysis, FFD and CCD model were employed to assess the effect of various parameters (concentration, pH, temperature and time). Results: The synthesis of nanoparticles was confirmed through different techniques. Synthesized nanoparticles exhibited the highest antibacterial activity against various microbes including multi‐drug resistant microbes compared to its individual constituents. DPPH and ABTS assays revealed high antioxidant activity of nanoparticles whereas, biocompatibility was assessed via MTT assay. The drug release profile confirms the sustained release of tetracycline molecules. Conclusions: We have successfully developed tetracycline conjugated copper oxide nanoparticles exhibiting potent antibacterial, antioxidant and biocompatible activity.

Preparation, optimization, and evaluation of ligand-tethered atovaquone-proguanil-loaded nanoparticles for malaria treatment

This work focused on improving antimalarial therapy through the development and characterization of Atovaquone-Proguanil-loaded nanoparticles employing a 32 factorial design. The nanoparticles were prepared from combinations of Poly(lactic-co-glycolic acid) (PLGA) and Eudragit L100 polymers and different concentrations of PVA (polyvinyl alcohol). Based on the results obtained the formulations were characterized for the particle size, zeta potential, encapsulation efficiency, and percent drug release. Among the nine formulations, F5 proved to be the most favorable in the biophysical parameters with a particle size of 176.3 nm, a zeta potential of −33.5 mV, and an encapsulation efficiency of 86% was found in the present investigation. Experimental dissolution profile analysis indicated that F5 had a slow and controlled-release profile where approximately 92.5%. Besides, cytotoxicity studies employing MTT, LDH (lactate dehydrogenase), and Trypan blue reduction test also supported the biocompatibility of nanoparticles and F5 had the highest cell viability (96%) with the least LDH release of 4%. In stability studies conducted for six months, F5 was found to remain stable regarding physicochemical characteristics and drug release profile at different temperature conditions such as room temperature, 4 °C, and 45 °C. The use of folic acid-functionalized nanoparticles is more effective, according to parasitemia, survival rate, and weight loss in mice treated with the nanoparticles. This is because functionalized nanoparticles could be used to enhance anti-malarial therapies.

Chemotherapeutic Drug Delivery Nanoplatform Development: From Physicochemical to Preclinical Evaluation

Through this study, the synergistic behavior of small-molecular-weight, amphiphilic surfactant molecules and the triblock copolymer Pluronic 188 was extensively evaluated based on their ability to formulate nanocarriers with novel properties for the delivery of class II and IV (biopharmaceutical classification system) chemotherapeutic compounds. The combination of four different surfactants at multiple weight ratios and twelve initially formulated nanosystems resulted in four hybrid delivery platforms, which were further studied in terms of multiple physicochemical characteristics, as well as their stability in protein-rich media (fetal bovine serum/phosphate-buffer saline). Finally, we obtained a single final nanoformulation that exhibited a high loading capacity (%EE ≥ 75%) and a sustained drug release profile under physiological conditions (model drug methotrexate), without altering the original physicochemical characteristics of the carrier. With a mean hydrodynamic radius (Rh) of less than 70 nm, a polydispersity index of 0.219, and no protein complexation, the system is a suitable candidate for in vivo, intravenous, and/or intramuscular administration. The cytotoxicity and genotoxicity of both loaded and unloaded carriers were evaluated through the examination of the upregulation or downregulation of apoptosis-related pathways. Multiple conventional 2D and 3D spheroidal conformations were used for these assessments, including HEK293, HCT-116, and MCF-7 cell lines, the results of which stressed the safety and biocompatibility of the empty nanocarrier. Additionally, experiments on Caenorhabditis elegans were conducted to evaluate the system’s in vivo toxicity, focusing on developmental stages, egg-laying behavior, and locomotion. Nanosystems studied in terms of chemotherapeutic encapsulation have mostly focused on the physiochemical aspect of the development of such novel delivery platforms, with only few exceptions proceeding step-by-step from cellular 2D to 3D to in vivo experimentation. The present study offers a holistic view of the behavior of such a novel system, advancing our understanding of the capabilities of polymeric/surfactant-based nanodelivery platforms.

Magneto-Thermal Hydrogel Swarms for Targeted Lesion Sealing.

Magnetic microswarms capable of performing navigation to targeted lesions show great potential for in vivo medical applications. However, using the swarms for lesion cavity filling encounters challenges from precise delivery and sealing. Herein, this work develops a magneto-thermal hydrogel swarm consisting of magnetic hydrogel particles, which can perform phase transition induced by temperature change. The particles are prepared using a temperature-responsive hydrogel matrix, tissue adhesive monomers, and magnetic microparticles. The swarms can be remolded to various shapes, and it can be used to seal perforation in phantom and gastric tissue. The swarms can also serve as drug carriers, and their drug release profiles induced by temperature changes are characterized. Finally, the targeted delivery, adaptive filling, and sealing of a gastric ulcer using the swarms are achieved in ex vivo and in vivo environments.

Development of Mathematical Function Control-Based 3D Printed Tablets and Effect on Drug Release.

The application of 3D printing technology in drug delivery is often limited by the challenges of achieving precise control over drug release profiles. The goal of this study was to apply surface equations to construct 3D printed tablet models, adjust the functional parameters to obtain multiple tablet models and to correlate the model parameters with the in vitro drug release behavior. This study reports the development of 3D-printed tablets using surface geometries controlled by mathematical functions to modulate drug release. Utilizing fused deposition modeling (FDM) coupled with hot-melt extrusion (HME) technology, personalized drug delivery systems were produced using thermoplastic polymers. Different tablet shapes (T1-T5) were produced by varying the depth of the parabolic surface (b = 4, 2, 0, -2, -4mm) to assess the impact of surface curvature on drug dissolution. The T5 formulation, with the greatest surface curvature, demonstrated the fastest drug release, achieving complete release within 4h. In contrast, T1 and T2 tablets exhibited a slower release over approximately 6h. The correlation between surface area and drug release rate was confirmed, supporting the predictions of the Noyes-Whitney equation. Differential Scanning Calorimetry (DSC) and Scanning Electron Microscope (SEM) analyses verified the uniform dispersion of acetaminophen and the consistency of the internal structures, respectively. The precise control of tablet surface geometry effectively tailored drug release profiles, enhancing patient compliance and treatment efficacy. This novel approach offers significant advancements in personalized medicine by providing a highly reproducible and adaptable platform for optimizing drug delivery.

Phase-separated polymer blends for controlled drug delivery by tuning morphology

Controlling drug release rate and providing physical and chemical stability to the active pharmaceutical ingredient are key properties of oral solid dosage forms. Here, we demonstrate a formulation strategy using phase-separated polymer blends where the morphology provides a route for tuning the drug release profile. By utilising phase separation of a hydrophobic and a hydrophilic polymer, the hydrophilic component will act as a channelling agent, creating a porous network upon dissolution that will dictate the release characteristics. With ptychographic X-ray tomography and scanning transmission X-ray microscopy we reveal how the morphology depends on both polymer fraction and presence of drug, and how the drug is distributed over the polymer domains. Combining X-ray imaging results with dissolution studies reveal how the morphologies are correlated with the drug release and showcase how tuning the morphology of a polymer matrix in oral formulations can be utilised as a method for controlled drug release.