Search Results (3,244)

Treating brain cancer remains challenging due to the blood–brain barrier (BBB) and the systemic toxicity of chemotherapy. This study focuses on developing human serum albumin (HSA) nanoparticles modified with low-molecular-weight protamine (LMWP) to improve crossing the BBB and enable targeted delivery of curcumin and temozolomide (TMZ). Nanoparticle stability was enhanced by crosslinking with aldehyde groups from oxidized gellan (OG). The successful attachment of LMWP to HSA at the thiol group of Cys34 was confirmed through FT-IR and ¹H-NMR analyses. Most self-assembled nanoparticles were smaller than 200 nm in diameter. Curcumin showed higher encapsulation efficiency than TMZ. In vitro drug release was pH-dependent: curcumin released more at pH 7.4, while TMZ release was better at pH 4. Higher crosslinking degrees reduced drug release. Cytotoxicity assays on V79-4 (normal) and C6 (glioma) cell lines showed increased apoptosis and significantly lower IC₅₀ values for co-encapsulated formulations, indicating a synergistic effect. Curcumin’s antioxidant activity was maintained and protected from UV degradation by the polymer matrix. The parallel artificial membrane permeability assay (PAMPA) confirmed that the functionalized formulations with co-encapsulated drugs could cross the BBB. Hemocompatibility studies indicated a favorable profile for intravenous use. Full article

Background/Objectives: The intranasal (IN) route of administration is a promising non-invasive approach for brain targeting, bypassing the blood–brain barrier and enhancing bioavailability. Citalopram hydrobromide (CT), a widely prescribed sparingly water-soluble selective serotonin reuptake inhibitor (SSRI), faces challenges with oral and intravenous administration, including delayed onset, adverse effects, and patient compliance issues. Methods: This study aimed to develop a novel thermoresponsive polymeric micelle (PM) system based on Pluronic^® copolymers (Pluronic F127 and Poloxamer 188) improving CT’s solubility, stability, and nasal permeability for enhanced antidepressant efficacy. A preliminary study was conducted to select the optimized formulation. The preparation process involved using the thin-film hydration method, followed by freeze-drying. Comprehensive evaluations of optimized formulation characteristics included Z-average, polydispersity index (PdI), thermal behavior (lower critical solution temperature, LCST), encapsulation efficiency, X-ray powder diffraction (XRPD), thermodynamic solubility, and biological stability. Additionally, in vitro CT release and CT permeability in nasal conditions were studied. Stability under storage was also evaluated. Results: The optimized CT-PM formulation showed nanoscale micelle size (Z-average of 31.41 ± 0.99 nm), narrow size distribution (polydispersity index = 0.241), and a suitable thermal behavior for intranasal delivery (lower critical solution temperature (LCST) ~31 °C). Encapsulation efficiency reached approximately 90%, with an amorphous structure confirmed via XRPD, leading to a 95-fold increase in CT solubility. The formulation demonstrated appropriate biological and physical stability. In vitro studies showed a 25-fold faster CT release from optimized formulation compared to the initial CT, while CT-PM permeability in nasal conditions increased four-fold. Conclusions: This novel nanoscale thermosensitive formulation is a value-added strategy for nasal drug delivery systems, offering enhanced drug solubility, rapid drug release, stability, and improved permeability. This smart nanosystem represents a promising platform to overcome the limitations of conventional CT administration, improving therapeutic outcomes and patient compliance in depression management. Full article

Background/Objectives: Radiotherapy can cause severe and irreversible brain damage, including cognitive impairment, increased dementia risk, debilitating depression, and other neuropsychiatric disorders. Current radioprotective drugs face limitations, such as single-target inefficacy or manufacturing hurdles. Isoliquiritigenin (ISL), a natural flavonoid derived from licorice root, exhibits broad bioactivities. It exhibits anti-inflammatory, anti-cancer, immunoregulatory, hepatoprotective, and cardioprotective activities. This study aimed to elucidate ISL’s neuronal radiation mitigation effects and key targets. Methods: In vitro and in vivo models of radiation-induced neuronal injury were established. ISL’s bioactivities were evaluated through cellular cytotoxicity assays, LDH release, ROS, ATP, glutamate, and GSH levels. In vivo, ISL’s radiation mitigation effect was evaluated with sucrose preference test, IL-β level, histopathological analysis, and Golgi-Cox staining analysis. Proteomics, pathway enrichment, and ensemble models (four machine learning models, weighted gene co-expression network, protein–protein interaction) identified core targets. Molecular docking and dynamic simulations validated ISL’s binding stability with key targets. Results: ISL attenuated radiation-induced cellular cytotoxicity, reduced LDH/ROS, restored ATP, elevated GSH, and mitigated glutamate accumulation. In rats, ISL alleviated anhedonia-like phenotypes and hippocampal synaptic loss. ISL also significantly suppressed radiation-induced neuroinflammation, as evidenced by reduced levels of the pro-inflammatory cytokine IL-1β. Proteomic analysis revealed that ISL’s main protective pathways included the synaptic vesicle cycle, glutamatergic synapse, MAPK signaling pathway, SNARE interactions in vesicular transport, insulin signaling pathway, and insulin secretion. Grm8, Grik3, and Grin3a were identified as key targets using the integrated models. The expression of these targets was upregulated post-radiation and restored by ISL. Molecular docking and dynamic simulations indicated that ISL showed stable binding to these receptors compared to native ligands. Conclusions: ISL demonstrates multi-scale radiation mitigation activities in vitro and in vivo by modulating synaptic and inflammatory pathways, with glutamate receptors as core targets. This work nominates ISL as an important natural product for mitigating radiotherapy-induced neural damage. Full article

Background: Large porous particles (LPPs) offer significant potential in drug delivery due to their porous structure and suitable particle size and shape, which can improve powder dispersibility and control drug release. Methods: In this study, sustained-release large porous microparticles of mannitol, PVA, and diclofenac sodium (MPDs) were developed using a spray drying technique. The influence of PVA co-spray drying and its concentration (0–40%) on the characteristics of the spray-dried particles was investigated. Results: Co-spray drying with PVA enhanced particle morphology, producing MPDs with a spherical shape and smooth surface, which minimized particle adhesion. This improvement correlated with a low Carr’s Index value (17.56%), indicating favorable particle dispersibility and aerosol performance. The large geometric diameter (>5 μm) of the MPDs, coupled with their low bulk density (<0.1 g/cm³), suggested potential for inhalation use. FTIR, XRD, and DSC analyses revealed that PVA altered the polymorphic form of mannitol, with the MPDs exhibiting a mixture of the α and δ forms. In vitro dissolution tests demonstrated that PVA co-spray drying effectively prolonged drug release, with the formulation containing 40% PVA (MPD-4) showing an optimal release profile. The release kinetics followed first-order Higuchi models, suggesting drug release occurred through a matrix diffusion mechanism facilitated by the porous structure. Conclusions: These findings demonstrate the feasibility of engineering large porous microparticles with tailored release characteristics and physicochemical properties suitable for further development in inhalable or other controlled-release dosage forms. Full article

The aim of this study was to evaluate liposomal particles as a potential delivery system for natamycin, a widely known antimicrobial agent used in the food industry. The goal was to prolong its diffusion into the surrounding medium. Natamycin-loaded liposomes were prepared using two methods (proliposome and thin-film) and two different phospholipid mixtures. The characterization of natamycin-loaded liposomes was performed in terms of their chemical composition (FT-IR analysis), encapsulation efficiency (EE), and antimicrobial potential against spoilage and pathogenic microorganisms that can be found in milk and milk products. During the 60-day storage period, their size, polydispersity index (PDI), and zeta potential were measured. The in vitro release kinetics of natamycin from liposomes were also assessed, and the results showed a significantly lower release rate of the drug when it was encapsulated. EE showed a high level of natamycin encapsulation (>80%), which was confirmed with FT-IR analysis. The stability study indicated that these systems were stable over a 60-day storage period, as the zeta potential of all formulations was ~−25 mV. Satisfactory antimicrobial performance of the developed liposomes against Listeria monocytogenes, Yersinia enterocolitica, Candida tropicalis, Candida parapsilosis, and Aspergillus flavus (MIC values from 0.00625 to 4 mg/mL) indicates that loading of natamycin into liposomal carriers was an adequate method for their encapsulation and delivery in the milk industry. Full article

Sim, a potent HMG-CoA reductase inhibitor, exhibits notable anabolic effects on bone and can upregulate osteogenic genes such as BMP-2, thereby promoting bone formation. An ideal drug delivery system for Sim involves its controlled and sustained release at the defect site to minimize adverse side effects. In this study, Sim was first modified via HP-γ-CD to form a hydrophilic Sim/HP-γ-CD inclusion complex, thereby improving drug solubility and dispersion in aqueous systems. A gelatin–sodium alginate (Gel/SA) hydrogel was then employed as the drug delivery matrix to construct a Gel-SA-Sim/HP-γ-CD hydrogel sustained release system. This hydrogel system exhibited a high water content (82%), along with enhanced mechanical properties, including a compressive strength of 0.284 MPa and a compressive modulus of 0.277 MPa, suggesting strong load-bearing capacity and favorable stiffness. Importantly, Sim was released in a controlled and sustained manner over 7 days, without exhibiting burst release behavior. In vitro osteogenic differentiation assays demonstrated that optimal concentrations of Sim effectively enhanced cellular bioactivity and osteoinductive performance, offering a promising approach to enhance the bioactivity, osteogenesis, and osseointegration of orthopedic implants. Full article

Background/Objectives: To improve the therapeutic efficacy of albendazole (ABZ) for ileocolonic diseases, its low solubility at higher pH levels should be enhanced. Organic acids have been widely used as pH modifiers to improve the solubility of weakly basic drugs. To achieve an adequate effect of the acidic microenvironmental pH during the drug release, pH modifiers should not leach out from the formulation. In the present work, we aimed to demonstrate that 100% tartaric acid pellets (TAP) can be used as pH-modifier cores, providing an acidic microenvironmental pH to enhance the solubility of albendazole at a higher pH. Methods: This study develops multilayer-coated pellets using TAP as starter cores in a bottom-spray-configured fluidized bed apparatus. The drug-layered TAP were coated with time-dependent and pH-dependent layers. Results: The release of ABZ from tartaric acid-based coated pellets was enhanced compared to that from pellets with the same layering structure but with an inert core of sugar or microcrystalline cellulose (MCC). In vitro experiments showed that tartaric acid remained in the pellet core during the dissolution test at a pH 6.8 medium, which resulted in an enhanced release of albendazole at a higher pH. The application of a combination of time-dependent and pH-dependent polymers aimed not only to prevent the release of albendazole at lower pH levels but also to protect TAP from premature release from the formulation. Conclusions: The application of 100% ready-to-use tartaric acid pellets (TAP) with the applied combination of coatings enhanced the solubility of the weakly basic drug albendazole at higher intestinal pH. Full article

Effective ocular drug delivery is still a challenge for pharmaceutical technologists due to the complex elimination mechanisms of the eye. In situ gels and polymeric micelles are among the pharmaceutical technologies that may enable us to overcome these challenges. Therefore, the objective of this study was to evaluate the ocular applicability of in situ gels and polymeric micelles, as well as their combinations, containing a steroidal anti-inflammatory drug, dexamethasone. The developed formulations were compared on the basis of their physicochemical characteristics, rheological behavior, mucoadhesion, in vitro drug release profile, and in vitro and ex vivo permeability. The developed formulations exhibited moderate stability according to the zeta potential measurements; however, they demonstrated appropriate mucoadhesion and sustained drug release. Furthermore, the results of the permeability studies suggest that combining thermoresponsive in situ gels and polymeric micelles represents a promising strategy for enhancing the therapeutic efficacy of ocular drug delivery. Full article

Background/Objectives: Reflecting the interaction between dissolution and absorption, the biphasic dissolution system is an appealing approach for estimating the intestinal absorption of drugs in humans. The study aims to characterize the suitability of the biphasic in vitro dissolution testing to set up an in vitro–in vivo correlation (IVIVC) for the original and generic immediate-release (IR) tablets of a Biopharmaceutics Classification System (BCS) Class II drug, bicalutamide (BIC). Methods: USP apparatus II paddle was used to conduct dissolution testing. A level A IVIVC was obtained between in vitro partitioning and in vivo absorption data of the original drug. The single-compartmental modeling was used for pharmacokinetic (PK) analysis. The generic product’s plasma concentrations were estimated. Results: There was a good correlation between in vitro and in vivo data (r² = 0.98). The area under the concentration–time curve (AUC) and maximum plasma concentration (C_max) ratios for generic/original were 1.04 ± 0.01 and 0.951 ± 0.026 (mean ± SD), respectively. Conclusions: The biphasic dissolution testing may present an in vivo predictive tool for developing generic products of poorly soluble and highly permeable drugs such as BIC, which are characterized by pH-independent poor solubility. Full article

Parkinson’s disease (PD) is recognized as one of the most common neurodegenerative disorders globally. The primary factor contributing to this condition is the loss of dopaminergic neurons, which results in both motor and nonmotor symptoms. The etiology of neurodegeneration remains unclear. However, it is characterized by the elevated production of reactive oxygen species, which subsequently leads to oxidative stress, lipid peroxidation, mitochondrial dysfunction, and inflammation. The investigation of the applicability of natural compounds and their derivatives to various diseases is becoming increasingly important. The possible role of curcumin from Curcuma longa L. and its derivatives in the treatment of PD has been partially investigated, but there are no data on the action of synthetic cyclic C₅-curcuminoids and chalcones tested in a Parkinson’s model. Two chalcones and five synthetic cyclic C₅-curcuminoids with potential antioxidant properties were investigated in an in vitro model of 6-hydroxydopamine (6-OHDA)-induced neurodegeneration in differentiated SH-SY5Y cells. Reactive oxygen species (ROS) production, total antioxidant capacity, antioxidant enzyme activity, thiol and ATP levels, caspase-3 activity, and cytokine release were examined after treatment with the test compounds. Based on these results, one cyclic chalcone (compound 5) and three synthetic cyclic C₅-curcuminoids (compounds 9, 12, and 13) decreased oxidative stress and apoptosis in our in vitro model of neurodegeneration. Compounds 5 and 9 were also successful in decreasing the production of pro-inflammatory cytokines (IL-6, IL-8, and TNF-α), while promoting the release of anti-inflammatory cytokines (IL-4 and IL-10). These findings indicate that these two compounds exhibit potential antioxidant, anti-apoptotic, and anti-inflammatory properties, rendering them promising candidates for drug development. Full article

Introduction: Plant-based phospholipid (PP) liposomes are sustainable, biocompatible, and biodegradable carriers with advantages over synthetic and animal-derived lipids, including lower immunogenic risk and abundant availability from sources such as soy, sunflower, and canola. This systematic review examines their characteristics, innovations, and applications in breast cancer (BCA) therapy. Methods: A total of 43 studies published between 2010 and June 2025 were identified from MEDLINE, Scopus, and Web of Science, focusing on PP composition, drug delivery mechanisms, and therapeutic efficacy in in vitro, in vivo, and preclinical BCA models. Results: Advances include nanotechnology and ligand-targeted systems that improve stability, control drug release, and enhance tumor-specific uptake. PP liposomes co-loaded with chemotherapeutics showed synergistic anticancer effects, increased tumor accumulation, and reduced systemic toxicity. Personalized targeting strategies further improved therapeutic precision and minimized off-target effects. Conclusions: PP liposomes offer an innovative and environmentally sustainable approach for BCA treatment with demonstrated preclinical benefits in efficacy and safety. Translation to clinical practice requires standardized characterization, scalable production, and well-designed trials to confirm safety, dosing, and long-term effectiveness. Full article

Background: The encapsulation of hydrophilic drugs within microparticles has gained significant interest in drug delivery systems due to their potential to improve stability, bioavailability, and controlled release of therapeutic agents. Biotin, a water-soluble vitamin, presents challenges such as rapid degradation and limited membrane permeability, which constrain its therapeutic effectiveness. Objectives: This study aims to develop and characterize biotin-loaded microparticles formulated with alginate, Eudragit^® E100, and CaCl₂, and to evaluate their characterization and potential applications. Methods: The microparticles were produced using the external ionic gelation method, where alginate and CaCl₂ solutions were mixed under probe sonication. Eudragit^® E100 was added as a complexing agent. The optimized formulation was used to encapsulate biotin, and various experimental variables were screened to study their influence on the properties of the microparticles. Results: Biotin was encapsulated in alginate microparticles (size: 634 nm; polydispersity index: 0.26; zeta potential: −45 mV) with an encapsulation efficiency of 90.5%. In vitro release studies using vertical diffusion Franz cells demonstrated a controlled release profile following the Weibull kinetic model. Conclusions: Encapsulation techniques offer a promising approach to overcome the limitations of hydrophilic drug delivery. The biotin-loaded microparticles developed in this study have potential applications in both topical and oral formulations, providing controlled release and improved therapeutic efficacy, and illustrate the broader applicability of polymeric encapsulation systems for improving the delivery of labile, hydrophilic bioactives. Full article

Angiotensin-converting enzyme 2 (ACE2) is a key mediator of SARS-CoV-2 host cell entry, making it an attractive target for drug delivery strategies. Nafamostat (NM), a multifunctional agent with antiviral and anti-inflammatory properties, holds promise for COVID-19 treatment. In this study, we developed PLGA-PEG nanoparticles encapsulating NM (NM-PP NPs) and further conjugated them with specific ACE2 decoys (CTC-445.2d or SI5α) to generate NM-PP-Pro/Pep NPs. Both unmodified and ACE2-decoy-modified NPs exhibited uniform size distributions (diameter < 200 nm) and negative surface charges, as confirmed by dynamic light scattering and zeta potential measurements. The nanoparticles maintained structural integrity for at least 18 days at 4 °C and room temperature. In vitro release studies revealed sustained and controlled NM release kinetics. Notably, NM-PP-Pro NPs displayed potent antiviral activity, with an IC₅₀ < 0.05 nM against wild-type SARS-CoV-2 and remained effective against the D614G variant (IC₅₀ = 2 nM). These results underscore the potential of NM-PP-Pro NPs as a versatile n;anotherapeutic platform for targeting SARS-CoV-2 and its emerging variants. Full article

Background/Objectives: The conventional treatment of glioblastoma (GBM) with alkylating agents is not curative. The protein O6-methylguanine DNA methyltransferase (MGMT) is a significant limitation, being able to repair drug-induced DNA damage. Thus, exploring non-alkylating agents already approved by the FDA is imperative. The antidepressant fluoxetine (FL) has been explored due to its anti-cancer properties. However, its first-pass effect and its non-targeted distribution to brain tissue are major limitations of FL’s administration, which is conventionally orally administered. Thus, the primary objective of this work was the development of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) tailored with folic acid (FA) for FL delivery to GBM cells. Methods: A Central Composite Design (CCD) was applied to optimize the NPs. Results: The developed FA-functionalized PLGA NPs exhibited physicochemical properties suitable for brain-targeted delivery. The final formulation presented an average diameter of 167 ± 8 nm, a polydispersity index (PdI) of 0.23 ± 0.07, and a zeta potential of −22.2 ± 0.3 mV. The encapsulation efficiency (EE) and loading capacity (LC) values were 44.4 ± 3.8% and 3.1 ± 0.3%, respectively. In vitro studies demonstrated that the NPs are stable in storage and simulated physiological conditions and can maintain a controlled and slow-release profile of FL for 17 days. In vitro cell uptake experiments demonstrated that conjugation with FA enhances the NPs’ internalization in GBM cells overexpressing folate receptors through endocytosis mediated by this receptor. Furthermore, in vitro cytotoxicity experiments demonstrated that the FL encapsulation in the developed NPs maintains drug efficacy, as well as it was able to increase cell sensitivity to treatment with an alkylating agent. Conclusions: These results suggest that the developed NPs are effective nanocarriers, either as a standalone therapy or as a chemosensitizer in combination with the standard GBM treatment. Full article

Significant efforts have been dedicated to developing controlled-release systems for the effective management of colorectal cancer. In this study, a once-daily, delayed-release regorafenib (REG) tablet was fabricated using 3D printing technology for the treatment of colorectal cancer. For this, a hydrogel containing 80 mg of the drug in a matrix of hyaluronic acid, carboxymethyl cellulose, Pluronic F127, and glycerol was prepared to incorporate into the shell cavity of tablet via a pressure-assisted microsyringe (PAM). The shell was printed from an optimized ink formulation of Soluplus^®, Eudragit^® RS-100, corn starch 1500, propylene glycol 4000, and talc through melt extrusion-based 3D printing. In vitro release assays showed a drug release rate of 91.1% in the phosphate buffer medium at 8 h and only 8.5% in the acidic medium. Drug release kinetics followed a first-order model. The results showed smooth and uniform layers based on scanning electron microscopy (SEM) and drug stability at 135 °C upon TGA. FTIR analysis confirmed the absence of undesired covalent interactions between the materials. Weight variation and assay results complied with USP standards. Mechanical strength testing revealed a Young’s modulus of 5.18 MPa for the tablets. Overall, these findings demonstrate that 3D printing technology enables the precise fabrication of delayed-release REG tablets, offering controlled-release kinetics and accurate dosing tailored for patients in intensive care units. Full article