Drug Bioavailability Research Articles

Cisplatin (CDDP), a widely used chemotherapeutic agent, is limited by severe ototoxicity side effects. Local drug delivery via the middle ear represents the most effective approach for treating inner ear disease. However, therapeutic efficacy is constrained by poor middle ear retention and limited permeability across the round window membrane (RWM). Quercetin (QU) exhibits potent activity against CDDP-induced cytotoxicity but suffers from delivery challenges. To address this, we developed amino-functionalized mesoporous silica nanoparticles (NH2-MSNs) loaded with QU (QU-N-MSNs), leveraging the permselective properties of the RWM. This system was noninvasively administered to the cochlea via trans-tympanic delivery. The synthesized QU-N-MSNs demonstrated a uniform particle size of approximately 116-124 nm, positive charge, and sustained drug release properties. Compared to free QU, QU-N-MSNs demonstrated significantly enhanced antiapoptotic and cytoprotective activities in vitro. In vivo studies confirmed nanoparticle retention within the inner ear for ≥14 days post administration and efficient RWM penetration. Pretreatment with QU-N-MSNs prior to CDDP exposure in murine models substantially mitigated ototoxicity, as evidenced by reduced hearing threshold shifts across multiple frequencies, preservation of hair cells (HCs) and spiral ganglion neurons (SGNs), and attenuation of mitochondrial-mediated SGN apoptosis. These findings establish QU-N-MSNs as an effective RWM-penetrating delivery platform, offering a promising strategy to enhance hydrophobic drug bioavailability in the inner ear and prevent CDDP-induced ototoxicity.

Comparison of dendritic mesoporous silica nanoparticles with commercial mesoporous excipients in improving physical stability and oral bioavailability of insoluble drugs

Nanoparticle-mediated transdermal systems can bypass the skin's natural outer barrier (stratum corneum), allowing drugs to enter the body more effectively. This technology improves how much drug reaches the bloodstream and how long it acts, which can make drug delivery noninvasive and more comfortable for patients. These technologies are engineered to markedly enhance drug permeability and bioavailability, while improving patient adherence and reducing systemic side effects. The incorporation of nanocarriers into transdermal systems can augment drug permeability across the skin by 2- to 10-fold, contingent upon the physicochemical characteristics of both the drug and the nanocarrier type, as demonstrated in multiple preclinical investigations. This review rigorously analyzes various nanocarriers, including liposomes, niosomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), polymeric nanoparticles, and inorganic nanostructures, and their effects on cutaneous and transdermal drug delivery. Improvements in entrapment efficiency of up to 90% and a three- to fivefold enhancement in drug retention within the epidermis have been recorded. Optimized nanoparticle-based formulations have also demonstrated sustained release characteristics lasting up to 72 h. Additionally, innovative technologies such as dissolving microneedles, nanoneedle arrays, luminous patches, and 3D-printed transdermal systems are examined regarding their capacity to enhance dosage accuracy, bioadhesion, and therapeutic efficacy. The study examines formulation characteristics such as polymer matrices, rate-controlling membranes, excipient compatibility, and penetration enhancers that affect the clinical efficacy and stability of nanoparticle-integrated patches. Significant attention is directed towards the impact of formulation choices on drug loading, release kinetics, and skin interaction patterns. Notwithstanding advancements, no nanoparticle-encapsulated transdermal patch has attained FDA approval to yet. The review delineates the principal translational obstacles-regulatory ambiguity, safety assessment, and GMP-scale production-and emphasizes the necessity for cohesive pharmacokinetic modeling, human skin correlation investigations, and real-time stability data to enhance clinical translation.

Synthesis of 1,3-diaryl substituted pyrazole-based imidazo[1,2-a]pyridine carboxamides and evaluation of their antitubercular activity.

Functional and morphological characterisation of human colonoid-derived monolayers under inflammatory conditions.

High-throughput analysis of aqueous drug solubility, supersaturation, and aggregation behaviour using second harmonic light scattering.

Machine learning-assisted classification and adulteration detection of fatty oils using fatty acid profiles obtained via supercritical fluid chromatography.

Biotinylated nanoparticles: A new frontier in nanomedicine and targeted cancer therapy.

Human coronaviruses (HCoVs), composed of the viruses causing severe acute respiratory illness described as the syndromes resulting from infection with respiratory coronaviruses (e.g., human immunodeficiency viruses (HIVs), whose incubation period averages 7 to 15 days and 1 to 6 months, respectively) and the newly emerged ones (e.g., human respiratory herpesvirus 6). The spread of new variants over a short period of time requires urgent and effective therapeutic strategies..This review discusses the potential of nano-chitosan biopolymeric nanoparticles as a promising therapy for combating SARS-CoV-2 and related viruses. The study examined the structural features, genome organization, and pathogenesis of the viral strains causing the current pandemic-SARS-CoV, MERS-CoV, and most recently, the viruses responsible for the current "coronavirus" syndication, namely, the newly discovered coronavirus - known as the "SAR-corona subgroup, viral genome organization, pathogenesis, and host/virus away within the SAR Coronavirus family. The role of nano-chitosan as an anti-viral agent and as a drug delivery enhancer for improved-drug bioavailability and targeted therapy is also reviewed in the context. Nano-chitosan shows a strong antiviral effect on HCoVs via enhancing drug solubility and bioavailability. Its capacity as a carrier able to transport antiviral agents, and in vaccine delivery, diagnostics, as well as in the field of therapeutic applications, is an important advance in nanomedicine. Nano-chitosan is a potential candidate for the future pandemic of coronavirus. The incorporation of nano-chitosan into therapeutic approaches may improve existing therapies as well as contribute to more effective control of viral outbreaks. Future

Pramipexole dihydrochloride (PPX) is a Biopharmaceutical Classification System (BCS) Class I drug with a short half-life, and its aqueous solution is susceptible to photodegradation. To improve its dosing convenience, the aim of this study was to prepare sustained-release solid dispersion (SD) pellets via hot-melt extrusion (HME) using ethyl cellulose (EC) and polyethylene glycol 6000 (PEG6000). The preparation process was optimized using single-factor experiments and central composite design (CCD). Under optimal conditions (PPX:EC ratio 1:4, 12.5% PEG6000, preparation temperature 155°C), the PPX solid dispersion (PPX-SD) showed stable performance and sustained release characteristics. SEM, DSC, and PXRD confirmed the amorphous state of PPX, while FT-IR indicated protential hydrogen bonding interactions between PPX and the polymers. In vitro release studies showed slower and more controlled release under pH 6.8. In vivo studies in rats demonstrated that PPX-SD had a four-fold higher AUC0-∞ (41.37 ± 9.39μg·h·mL-1) compared to the commercial formulation Sifrol® (9.52 ± 2.18μg·h·mL-1, p < 0.05). Tissue distribution studies in rats revealed increased brain accumulation of PPX in the PPX-SD group. Thus, PPX-SD exhibited a sustained-release and markedly improved the bioavailability by maintaining supersaturated amorphous substances, inhibiting precipitation during the drug absorption phase. This formulation offers a robust scientific foundation for the treatment of Parkinson's disease.

Advances in the construction and application of transdermal delivery systems.

Depression is a debilitating mental disorder closely linked to neuroinflammation and dysregulated microglial activity. This study investigates a novel nanotherapeutic strategy utilizing geniposide (GEN)-loaded biomimetic nanoparticles (CSPG@CM) to target microglia and modulate heme oxygenase-1 (HMOX1), a key regulator of oxidative stress and neuroinflammation. Through the synergistic application of systems pharmacology frameworks, computational biological analysis, and both cell-based and animal experimental models, this study demonstrated that GEN-loaded nanoparticles significantly enhance drug bioavailability and specificity, facilitating precise microglial targeting. Treatment with CSPG@CM nanoparticles upregulates HMOX1 expression, suppresses pro-inflammatory cytokine release, and promotes neuronal survival. In a chronic unpredictable mild stress (CUMS) mouse model, CSPG@CM nanoparticles alleviate depressive behaviors, reduce neuroinflammation, and restore neuronal homeostasis. Compared to free GEN, the nanoparticle formulation exhibits superior therapeutic efficacy by overcoming limitations in traditional antidepressant treatments. These findings highlight the potential of nanoparticle-based drug delivery systems for precise modulation of neuroinflammatory pathways, offering a promising avenue for developing innovative antidepressant therapies.

ABSTRACT Epilepsy is a disease that arises from the disruption of nerve conduction in different parts of the brain due to intense and repetitive discharge of nerve cells, and some of the symptoms manifest through seizures. The low bioavailability of antiepileptic drugs (AEDs) used for treatment and the inability to administer drugs orally during seizures highlight the need for new drug delivery systems. In the present study, the effect of ethosuximide (ETX) supplementation to polylactic acid (PLA)/bismuth ferrite (BFO, BiFeO 3 ) mixture on epileptic seizures was investigated in detail. ETX‐loaded fibers were created by adding ETX in different ratios (10, 15, and 20 mg) through the same procedures. The morphological analysis showed that the minimum diameter belonged to the 10% PLA fibers. According to the tensile testing results, the 10% PLA + 5 mg BFO fiber had the highest tensile strength value (2.49 ± 1.01 MPa). The biocompatibility results, performed with the human neuroblastoma cell line (SH‐SY5Y), demonstrated that all fibers had no cytotoxic effect. The ETX release was performed both under and without an electric field in vitro conditions. The results demonstrated that the ETX released faster from fibers under an electric field.

Most available data on the composition and solubilizing properties of postprandial human intestinal fluid (HIF) are derived from studies involving liquid meals. These data inform the development of simulated intestinal fluids, widely used in in vitro assays for predicting intestinal drug behavior. However, the typical human diet primarily consists of solid meals, and the physical form of food has been shown to influence gastrointestinal transit and digestion, thereby affecting drug disposition and bioavailability. This study compares the characteristics of fed-state HIF collected after solid meal ingestion (SM-HIF) with previously published data on pooled liquid meal-derived HIF (LM-HIF) and newly generated data from individual LM-HIF samples. Time-dependent samples were analyzed over 180- and 90 min postprandial sampling periods to assess compositional changes following the administration of a solid and liquid meal, respectively. In addition, pooled samples were used to evaluate the solubilizing capacity for seven lipophilic model compounds. After intake of the solid meal, duodenal concentrations of exogenous (lipids, cholesterol, proteins) and endogenous (bile salts, phospholipids) components gradually increased to peak levels reached after 45-75 min. After 180 min, lipid and protein concentrations were still elevated compared to fasted state levels. In comparison to the liquid meal, the ingestion of the solid meal resulted in reduced concentrations of exogenous components, while endogenous components (bile salts and phospholipids) were relatively similar. For most compounds, the reduction in lipid content led to diminished solubilizing capacity of SM-HIF compared to LM-HIF when considering the combined micellar and lipid fractions. In contrast, the solubilizing capacity of the micellar fraction as such was largely independent of the meal type. Both the composition (particularly the micellar lipid concentration) and the solubilizing capacity of SM-HIF were highly variable between pools, albeit to a lesser extent than in LM-HIF. The findings of this study highlight that the physical form of the meal influences the composition and solubilizing capacity of HIF. These insights should be taken into account when refining biorelevant media for in vitro models to better predict food effects during drug product development.

This study evaluates the mucoadhesive properties of Opuntia-carrageenan superporous hydrogel (OPM-CRG SPH) in vitro and in vivo, assessing its potential as a biomaterial for gastrointestinal (GI) mucoadhesive drug delivery systems.Mucoadhesive polymers are critical for anchoring drug delivery devices to specific mucosal sites, enabling localized and sustained drug presence. By prolonging residence time at the site of application, such biomaterials hold the potential to improve drug bioavailability and therapeutic outcomes, particularly in GI delivery platforms. This research explores the mucoadhesive performance of OPM-CRG SPH, which could advance the development of effective GI mucoadhesive drug delivery systems.In vitro mucoadhesion was tested using goat GI mucosa and a texture analyzer, measuring key parameters such as work of adhesion (Wad) and maximum detachment force (Fmax) under varying instrumental conditions. In vivo GI-retention studies were conducted on New Zealand rabbits, using X-ray radiography to monitor the formulation's retention in the GI tract (GIT).Mucoadhesion increased with contact time and force but exhibited minimal change by withdrawal speed. Distinct mucoadhesive behaviors were observed across different GIT segments, with the highest Fmax and Wad values recorded in large intestinal tissues. In vivo studies confirmed maximum adherence at higher pH levels, consistent with in vitro findings. X-ray imaging demonstrated successful 8 to 10-h mucoadhesion in rabbits.The hydrogel exhibits promising mucoadhesive properties, making it a viable candidate for GI drug delivery systems. Its ability to adhere effectively across various GI segments and sustain prolonged retention highlights its potential for enhancing drug delivery efficiency.

Niclosamide, a well-known anthelmintic drug used against parasitic infections, has gained attention for its potent anticancer and antibacterial activity. However, the use of niclosamide remains limited due to its highly hydrophobic nature and low systemic bioavailability. To address these limitations, we developed a biocompatible drug delivery system to combat the challenges of niclosamide usage. We fabricated niclosamide-loaded polycaprolactone (PCL) and poly(ethylene oxide) (PEO) composite nanofibers and investigated their anticancer and antibacterial applications. Here, PEO enhances drug diffusion and bioavailability, while PCL provides biodegradability and controlled drug release properties. Four different compositions of PEO-PCL nanofibers were synthesized and infused with niclosamide. The synthesized nanofibers were thoroughly characterized by using field emission scanning electron microscopy (FE-SEM), Fourier-transform infrared spectroscopy (FTIR), and energy-dispersive X-ray (EDX) analysis, confirming successful drug incorporation. To test the functionality of fabricated nanofibers, we examined the antibacterial properties using a minimum inhibitory concentration (MIC) and minimum killing concentration (MKC). Interestingly, these nanofibers have a significant activity against Staphylococcus aureus (Gram-positive) but not against Escherichia coli (Gram-negative), suggesting selective action. Furthermore, we assessed the anticancer potential of drug-loaded nanofibers in HeLa cells using a cell cytotoxicity assay. A marked decrease in cell viability was observed when the cells were treated with niclosamide-loaded nanofibers. Collectively, our findings demonstrate that niclosamide-loaded PEO-PCL nanofibers are a promising and efficient drug delivery system with potential applications in antimicrobial and anticancer therapies.

ABSTRACT Macromolecules have emerged as transformative agents in drug delivery, significantly enhancing therapeutic efficacy, stability, and precision. These high molecular weight biomolecules, including nucleic acids, proteins, polysaccharides, and synthetic polymers, play a vital role in improving drug solubility, ensuring controlled release, and enabling targeted delivery while minimizing adverse effects. Recent advancements in material science and nanotechnology have led to the development of innovative drug delivery platforms such as hydrogels, dendrimers, liposomes, polymeric micelles, and nanoparticles. These sophisticated systems allow for precise drug administration, reducing toxicity and optimizing therapeutic outcomes. By leveraging macromolecular properties, researchers have enhanced drug bioavailability, improved targeting specificity, and enabled sustained and controlled drug release. The integration of macromolecules with nanotechnology is driving the next generation of drug delivery systems, offering groundbreaking solutions in nanomedicine.

The enhancement of drug solubility and bioavailability is a significant challenge in pharmaceutical sciences. Solid dispersions have emerged as a promising strategy to address this issue. This research provides a comprehensive review of the advancements in solid dispersion technologies, focusing on the classification and characteristics of different generations of solid dispersions. The study highlights the evolution from first-generation solid dispersions, utilizing crystalline carriers, to fourth-generation systems that incorporate water-insoluble polymers and surfactants to improve drug release and bioavailability. The efficacy of various carriers and techniques, such as hot melt extrusion and solvent evaporation, is critically analyzed. Additionally, the impact of these advancements on poorly soluble anticancer drugs and herbal medicines is discussed, providing insights into future research directions and potential therapeutic applications.

Bacterial conjunctivitis is a common eye infection caused by bacteria, posing significant treatment challenges due to rising antibiotic resistance and the limitations of traditional therapies. Standard treatments, including topical antibiotics, often suffer from issues such as poor bioavailability, limited effectiveness, and patient adherence. Nanotechnology offers an innovative approach, providing potential solutions for more effective drug delivery, diagnostics, and therapeutic interventions. The objective of this study is to explore the role of nanotechnology in improving the management of bacterial conjunctivitis. Specifically, it examines how nanostructured drug carriers, such as nanoparticles, nanogels, and liposomes, can enhance ocular drug delivery and therapeutic outcomes. A key focus is on the influence of the hydrodynamic radius (Rh) in optimizing stability, solubility, and bioavailability. Nanotechnology has shown promise in improving the delivery of drugs for bacterial conjunctivitis by enhancing ocular penetration and prolonging the release of active agents. The hydrodynamic radius (Rh) of nanoparticles plays a critical role in stabilizing the colloidal structure of the formulation, preventing aggregation and sedimentation. Furthermore, optimizing Rh can increase the surface area-to-volume ratio, which is beneficial for improving the solubility of poorly soluble drugs, thereby enhancing their bioavailability. Nanotechnology- based systems can also enable the development of diagnostic tools, such as nanosensors, capable of quickly and accurately detecting bacterial pathogens, facilitating timely, targeted treatments and reducing unnecessary use of broad-spectrum antibiotics. The precise control of nanoparticle Rh enhances drug stability, bioavailability, and sustained release, ultimately improving patient compliance and therapeutic efficacy. The future of bacterial conjunctivitis treatment is promising, with further research focused on optimizing nanoparticle characteristics such as size, surface modification, and targeted drug delivery. However, challenges remain, particularly concerning the safety of nanoparticles, including potential risks to ocular tissues and long-term effects. Continued research, including in vitro and in vivo studies as well as clinical trials, is essential to establish the safety and clinical viability of these nanotechnology-based systems. With further advancements, nanotechnology could revolutionize treatment strategies for bacterial conjunctivitis, offering more targeted, patient-centered, and effective solutions for managing ocular infections and combating antibiotic resistance.

Bio-based surface-active ionic liquids (SAILs) offer promising advantages for pharmaceutical applications, particularly in enhancing drug solubility and bioavailability. Aspirin, classified under the Biopharmaceutics Classification System (BCS) as poorly soluble in the gastrointestinal tract, require effective solubilization strategies for improved therapeutic efficacy. This study investigates the micellization behavior and thermophysical properties of three natural based SAILs (2-hydroxyethyl)ammonium oleate ([2-HEA][Ole]), bis(2-hydroxyethyl)ammonium oleate ([BHEA][Ole]), and tris(2-hydroxyethyl)ammonium oleate ([THEA][Ole]) in aqueous solutions of aspirin at 298K. Micellization characteristics, including critical micelle concentration (CMC), were determined using electrical conductivity and surface tension measurements for SAILs in the presence of the aspirin aqueous solutions systems at 298K. Key interfacial parameters such as interface surface pressure (Π),minimum surface area occupied per molecule ([Formula: see text]),Gibbs maximum excess surface concentration ([Formula: see text]) were also calculated. Additionally, the Conductor-like Screening Model (COSMO) was employed to elucidate molecular interactions between SAILs and the studied drug. The results indicate that CMC values decrease in the presence of aspirin. Among the studied systems, [THEA][Ole] exhibited the lowest CMC, as determined by electrical conductivity and surface tension measurements, particularly in the presence of higher concentrations of aspirin in aqueous media. Furthermore, COSMO analysis revealed that [THEA][Ole], possessing the highest surface cavity volume(V), demonstrated the most favorable interactions with aspirin, highlighting its potential as an effective solubilizing agent. Finally, interactions between SAILs and aspirin were investigated through limiting molar conductivity[Formula: see text] , and association constant[Formula: see text] , determination.