Search Results (120)

Background/Objectives: This study aimed to repurpose aripiprazole (AR), an antipsychotic clinically approved by the FDA, as a novel antifungal drug and to potentiate its therapeutic efficacy through PEGylated terpesomes (PEG-TERs). Methods: PEG-TERs were prepared by thin-film hydration and optimized using a central composite design. The optimum PEG-TER formulation was characterized for entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP), and subsequently integrated into polylactic acid (PLA)-based 3D-printed ocuserts. Results: The optimized formulation exhibited spherical vesicles with high EE%, nanoscale PS, narrow PDI, and favorable ZP, alongside excellent stability and mucoadhesive properties. Ex vivo permeation demonstrated a sustained release profile of AR from PEG-TERs compared with an AR suspension, while confocal microscopy confirmed efficient corneal deposition of fluorescein-labeled PEG-TERs. In vivo, the optimum AR-loaded PEG-TERs ocusert exhibited a substantial therapeutic effect in a rabbit model of Candida albicans keratitis, while histopathological assessment confirmed its ocular safety and biocompatibility. Conclusions: In conclusion, AR-loaded PEG-TERs embedded in PLA-based 3D-printed ocuserts represent a promising, safe, and innovative therapeutic platform for the management of Candida albicans-induced corneal infections, offering both drug repurposing and emerging opportunities in advanced ocular drug delivery. Full article

Background/Objectives: Cachexia is a syndrome characterized by the progressive loss of muscle mass, leading to high morbidity and mortality. Ghrelin (Ghrl) exhibits orexigenic, anabolic, and anti-inflammatory properties with therapeutic potential. However, its low bioavailability limits the efficacy of systemic treatments. This study aimed to develop chitosan-coated liposomes containing Ghrl (CH-Lip + Ghrl) for intranasal administration, allowing quantification of Ghrl brain bioavailability using a system optimized for a labile neuropeptide. Methods: The formulation was prepared using thin-film hydration, followed by extrusion and chitosan coating. It was characterized based on morphology, size, zeta potential, stability, encapsulation efficiency, and cell viability. Permeation and mucoadhesion were evaluated ex vivo using porcine nasal mucosa, and cerebral bioavailability was assessed in Wistar rats. Results: CH-Lip + Ghrl had an average of 152.4 ± 0.2 nm (evaluated by DLS), a polydispersity index of 0.159 ± 0.018, a zeta potential of +60.8 ± 6.6 mV, and an encapsulation efficiency of 53.2 ± 0.8%, maintaining stability for 180 days. At 1% (v/v) in culture medium, the formulation retained 73.2 ± 8.4% of the viability in nasal epithelial cells and 81.9 ± 4.8% in neuroblastoma cells. Chitosan coating increased ex vivo mucoadhesion 1.7-fold and permeation 1.3-fold. In vivo, 25 min after intranasal administration, CH-Lip + Ghrl delivered 48.2 ± 8.8% of the dose to the brain, whereas free Ghrl was undetectable. Conclusions: The intranasal administration of CH-Lip + Ghrl enhances cerebral bioavailability of Ghrl. This study integrates a chemically labile neuropeptide with chitosan-coated liposomes for direct brain delivery, representing an innovative platform for future translational studies. Full article

Background/Objectives: Sublingual vaccination offers a non-invasive route for inducing both systemic and mucosal immunity, yet the formulation properties that govern its success remain poorly defined. This study investigated the relationships among key formulation parameters for sublingual vaccines, such as viscosity, mucoadhesion, and mucosal residence, to understand their impact on in vivo immune responses in the sublingual delivery context. Methods: Ovalbumin (OVA)-based vaccine formulations containing cholera toxin B (CTB) adjuvant and mucoadhesive excipients such as hydroxypropyl methylcellulose (HPMC) or methylglycol chitosan (MGC), were evaluated for: (1) their respective rheological properties—characterized by viscosity and mucoadhesion parameters, as well as (2) in situ mucosal retention (assessed using Cy7-labeled formulations tracked by IVIS in vivo imaging system) and (3) in vivo immunogenicity via systemic (IgG) and mucosal (IgA) responses measured by ELISA, following sublingual administration to mice. Correlations between rheology, in situ/ex situ mucosal residence, and in vivo immune outcomes were determined. Results: Sublingual vaccine formulations containing HPMC exhibited the highest viscosity, mucoadhesion, and mucosal retention profiles, but paradoxically elicited the weakest systemic and mucosal antibody responses. In contrast, chitosan-based formulations enhanced immune responses even at reduced antigen and adjuvant doses, likely due to its permeation-enhancing and adjuvant effects. Correlation analyses revealed that while formulation viscosity and mucoadhesive strength were positively associated with mucosal retention, both rheological and retentive properties showed a significant inverse relationship with immunogenicity in the context of sublingual vaccine delivery. Conclusions: While viscosity and mucoadhesion are essential for in situ retention of sublingual vaccines, prolonged residence driven by excipient’s excessive rheological strength was found to reduce vaccine immunogenicity—likely due to restricted antigen release and mucosal uptake. Accordingly, HPMC appears suboptimal as a sublingual vaccine excipient, while chitosan shows promise for sublingual delivery as a permeation-enhancing adjuvant. These findings may shift the design paradigm for sublingual vaccine formulations, highlighting the need to balance mucosal retention with efficient antigen absorption for maximizing immune responses. Full article

Background/Objectives: The oral administration of chemopreventive agents for colorectal cancer (CRC) remains limited by their low solubility, instability, and limited intestinal absorption. This study develops sodium carboxymethyl cellulose (CMC)-stabilised water-in-oil-in-water (W/O/W) multiple emulsions as pH-responsive carriers for co-delivery of resveratrol and selenium—two complementary chemopreventive compounds. Methods: Multiple emulsions differing in droplet size (small-droplet emulsions, SDE; large-droplet emulsions, LDE) and CMC concentration (0.0–0.5% w/w) are prepared in a Couette–Taylor Flow contactor. The study involves physicochemical characterisation of emulsions (droplet size, stability, rheological behaviour, ζ-potential, encapsulation efficiency), evaluation of release profiles under simulated gastric pH (2.0) and intestinal pH (7.0) conditions, including pathological environments (pH = 5.5), and ex vivo assessment of mucoadhesion using porcine intestinal tissue. Results: SDE and LDE containing CMC (0.0–0.5% w/w) exhibit a complex “drop-in-drop” structure, with Sauter mean diameters of approximately 9–12 μm and 23–25 μm, respectively, and high encapsulation efficiencies (>91%). Increasing CMC concentration enhances viscosity and induces more negative ζ-potential, confirming polymer adsorption at the oil–water interface. Under simulated gastric pH = 2.0, compound release remains limited (≤15%), whereas gradual/sustained release is observed under simulated intestinal pH (5.5/7.0). Mucoadhesion increases with polymer concentration, reaching ~90% for SDE and ~70% for LDE at 0.5% w/w CMC, and remains above 50% under simulated pathological conditions. Conclusions: The study demonstrates that CMC incorporation improves the structural stability, modulates the release behaviour, and enhances the mucoadhesive properties of W/O/W multiple emulsions. These findings suggest that CMC-stabilised emulsions may be further explored as oral delivery vehicles for CRC chemoprevention. 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

Intermittent catheterization mitigates urinary retention for over 300,000 people in the US every year, but can cause microtrauma in the urothelium, compromising its barrier function and increasing the risk of pathogen entry, which may affect user health. To reduce adverse effects, intermittent catheters (ICs) with increased lubricity are used. A common strategy to enhance IC lubricity is to apply a polyvinylpyrrolidone (PVP) coating to ICs; however, this coating can become adhesive upon drying, potentially leading to microtrauma. An alternative approach for lubricity is the migration of integrated amphiphilic surfactant (IAS) within the IC to the surface. The present work examines differences in urethral microtrauma caused by the simulated catheterization of ex vivo porcine urethral tissue using PVP-coated and IAS ICs. Scanning electron microscopy and fluorescence microscopy of the tissue showed the removal of the apical cell layer after contact with the PVP-coated ICs, but not the IAS IC. More extracellular matrices and DNA were observed on the PVP-coated ICs than the IAS IC after tissue contact. Contact angle analysis of the polar and dispersive components of the surface energy demonstrated that the PVP-coated ICs promoted mucoadhesion, while the IAS IC limited mucoadhesion. Overall, the results indicate that IAS ICs cause less microtrauma to urethral tissue than traditional PVP-coated ICs. Full article

Periodontitis is a prevalent oral condition worldwide. Azithromycin, a conventional lipophilic drug for periodontal treatment, often causes systemic side effects when administered orally. To address this, azithromycin-loaded nano-emulgels were developed using olive oil as a carrier within a xanthan gum aqueous gel phase. This oil-in-aqueous gel emulsion was actuated into a foam for localized drug delivery in gingival and periodontal disease. The solubility of azithromycin in various vehicles was tested, with olive oil showing the best solubility (0.347 mg/mL). Thermodynamic stability testing identified viable nano-formulations, with encapsulation efficiencies ranging from 98 to 100%. These formulations exhibited rapid drug release within 2–8 h. Muco-adhesion studies and ex vivo permeability tests on porcine buccal mucosa highlighted the beneficial properties of xanthan gum for local drug retention within the oral cavity. Antimicrobial efficiency was assessed using minimum inhibitory concentrations against various oral pathogens, where the formulation with equal surfactant and co-surfactant ratios showed the most potent antibacterial activity, ranging from 0.390 to 1.56 µg/mL. This was supported by the shear-thinning, muco-adhesive, and drug-retentive properties of the xanthan gel base. The study also examined the influence of the oil phase with xanthan gum gel on foam texture, rheology, and stability, demonstrating a promising prototype for periodontitis treatment. Full article

Background: Folic acid (FA) is essential for cellular functions but has limited ocular bioavailability, restricting its therapeutic effectiveness. Objective: To develop chitosan (CS)-based nanogels (NGs) for FA transport and release, with corneal permeation evaluation. Methods: NGs’ hydrodynamic diameter (Ho) and polydispersity index (PdI) were determined using dynamic light scattering (DLS). CS-FA interaction was confirmed by Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA) was applied for the dehydrated material characterization. Scanning electron microscopy (SEM) was used to evaluate the NGs ultraestructure. In vitro drug release studies were performed using a modified Franz diffusion cell, and the release profile was fitted to obtain kinetics parameters. Mucoadhesion properties were evaluated through ζ-potential measurements. Ex vivo corneal permeation studies were conducted in rabbit corneas to compare the permeability of FA contained in NGs. Results: NGs presented a Ho of 312.4 ± 8.2 nm and a PdI of 0.28 ± 0.04. SEM imaging revealed spherical morphologies with minor variations in size and shape induced by FA. Lyophilized and resuspended NGs exhibited a 6.8% increase in Ho and a PdI rise to 0.42, indicating slight aggregation. In vitro drug release studies demonstrated sustained FA release, as determined by the Higuchi model. Mucoadhesion studies showed a decrease in ζ-potential from +36.9 to +18.1 mV, confirming electrostatic interactions with mucin. Ex vivo corneal permeation studies indicated that encapsulated FA permeated 2.6 times slower than free FA, suggesting sustained release. Conclusions: our findings demonstrate the potential of nanostructures in the form of NGs to enhance FA-loaded ocular delivery and bioavailability. Full article

Buccal drug delivery systems often struggle with poor drug solubility, limited adhesion, and rapid clearance, leading to suboptimal therapeutic outcomes. To address these limitations, we developed a novel hybrid eutectogel composed of xanthan gum (XTG), hyaluronic acid (HA), and a Natural Deep Eutectic Solvent (NADES) system (choline chloride, sorbitol, and glycerol in 2:1:1 mole ratio), incorporating 2.5% ibuprofen (IBU) as a model drug. The formulation was optimized using a face-centered central composite design to enhance the rheological, textural, and drug release properties. The optimized eutectogels exhibited shear-thinning behavior (flow behavior index, n = 0.26 ± 0.01), high mucoadhesion (adhesiveness: 2.297 ± 0.142 N·s), and sustained drug release over 24 h, governed by Higuchi kinetics (release rate: 237.34 ± 13.61 μg/cm²/min^1/2). The ex vivo residence time increased substantially with NADES incorporation, reaching up to 176.7 ± 23.1 min. An in vivo anti-inflammatory evaluation showed that the eutectogel reduced λ-carrageenan-induced paw edema within 1 h and that its efficacy was sustained in the kaolin model up to 24 h (p < 0.05), achieving comparable efficacy to a commercial 5% IBU gel, despite a lower drug concentration. Additionally, the eutectogel presented a minimum inhibitory concentration for Gram-positive bacteria of 25 mg/mL, and through direct contact, it reduced microbial viability by up to 100%. Its efficacy against Bacillus cereus, Enterococcus faecium, and Klebsiella pneumoniae, combined with its significant anti-inflammatory properties, positions the NADES-based eutectogel as a promising multifunctional platform for buccal drug delivery, particularly for inflammatory conditions complicated by bacterial infections. Full article

The aim of this study was to develop a thermosensitive mucoadhesive (MA) in situ nasal gel for sumatriptan. A 3D response surface methodology (Design of Expert version 11) was employed to formulate nine different formulations. The Pluronic F-127 concentration (X1) and chitosan concentration (X2) were selected as independent factors. The formulas were studied in terms of pH, clarity, drug content, gelation temperature, gelation time, gel strength, MA strength, viscosity, % release after 5 h, and release kinetics. The optimized formulas were studied for % permeated after 5 h and stability in addition to previous tests. The study of the stability of the optimized formula was performed under accelerated conditions (40 ± 2 °C, 75 ± 5% RH) for 3 months. The outcomes of the optimized formula were a clear gel with a gelation temperature of 33 °C and a reasonable gelation time of less than one minute, and the release and permeation during 5 h were 40% and 50%, respectively. The formulated gel decreased the mucociliary clearance (MCC) and thus increased the retention time in the nasal cavity, resulting in enhancing SMT absorption, which could improve the drug efficacy. Full article

Imipramine hydrochloride (IMP), a tricyclic antidepressant used for major depression, enuresis, and neuropathic pain, is limited by gastrointestinal complications, low oral bioavailability (44%), and complex dosing requirements. This study aimed to explore a novel non-invasive nasal delivery system using chitosan nanoparticles (Cs NPs) embedded in an in situ gel to address the limitations of oral IMP administration. Cs NPs loaded with IMP were synthesized via ionic gelation and assessed for precision in drug concentration using a validated HPLC method. The particles were integrated into a thermoresponsive polymer, Pluronic F127, to form an in situ gel suitable for nasal administration. The formulation was characterized for gelation temperature, duration, viscosity, mucoadhesive strength, and overall gel robustness. Drug release kinetics and the controlled release mechanism were studied using ex vivo permeation tests with Franz diffusion cells and nasal sheep mucosa. The optimized nanoparticle formulation (F4-50) exhibited a consistent PS of 141.7 ± 2.2 nm, a zeta potential (ZP) of 16.79 ± 2.1 mV, and a high encapsulation efficiency of 67.71 ± 1.9%. The selected in situ gel formulation, F4-50-P1, demonstrated a gelation temperature of 33.6 ± 0.94 °C and a rapid gelation time of 48.1 ± 0.7 s. Transform-attenuated total reflectance infrared spectroscopy (ATR-IR) confirmed the compatibility and effective encapsulation of IMP within the formulation. The release profile of F4-50 included an initial burst release followed by a sustained release phase, with F4-50-P1 showing improved control over the burst release. The flux rates were 0.50 ± 0.01 mg/cm²/h for F4-50 and 0.33 ± 0.06 mg/cm²/h for F4-50-P1, indicating effective permeation. The developed chitosan nanoparticle-based in situ gel formulation provides a promising approach for the controlled release of IMP, enhancing therapeutic efficacy and patient compliance while mitigating the disadvantages associated with oral delivery. Full article

Background/Objectives: Patients with schizophrenia have significant challenges in adhering to and complying with oral medicines, resulting in adverse consequences such as symptom worsening and psychotic relapse. Methods: This study aimed to develop clove oil-based bilosomes using definitive screening design (DSD) to maximize the anti-schizophrenic action of clozapine and promote its nose-to-brain delivery. The target was to optimize the physicochemical properties of bilosomes and incorporate them into mucoadhesive intranasal in situ gels, searching for augmented ex vivo and in vivo clozapine delivery. Results: The bilosomes’ particle size was decreased by increasing the span, SDC, and clove oil amounts. In addition to using a high lipid amount, the aforementioned components also helped increase the entrapment efficiency values. Increased zeta potential was only observed by increasing surfactant amount and reducing clozapine concentration. After incorporation of optimized liquid clove oil-based bilosomes, which had a spherical nano-sized vesicular shape, into P 407-dependent gels, an HPMC (2% w/w)/P 407 (20% w/w)-containing formulation (G6) was selected as an optimized gel owing to its acceptable gelation time (13.28 s), gel strength (27.72 s), viscosity (12,766.67 cP), and mucoadhesive strength (4273.93 dyne/cm²). The optimized G6 exhibited higher J_ss (50.86 μg/cm²·h⁻¹) through the nasal mucosa compared to the control gel (23.03 μg/cm²·h⁻¹). Compared to the control gel, G6 displayed higher relative bioavailability (491.37%) than a commercial tablet (264.46%). Following ELISA analysis, dopamine and serotonin were significantly reduced, while BDNF was remarkably increased after administration of optimized G6 into schizophrenic rats. Conclusion: Our study indicates the potential of intranasal bilosomal gels in upgrading the anti-schizophrenic and neuroprotective activity of clozapine. Full article

Loratadine (LOR) is a second-generation antihistamine that exhibits a low and variable oral bioavailability (10–40%) and delayed onset owing to poor solubility and an extensive first-pass effect. Therefore, in light of the clinical need, the main goal of the present study was to develop sublingual fast-dissolving thin films of LOR–citric acid co-amorphous systems (LOR-CAs) with the aim of eliciting a faster onset and improving the bioavailability. We formulated sublingual fast-dissolving thin films of LOR by a film-casting technique using hydrophilic polymers like hydroxypropyl methylcellulose (HPMC E15), polyvinyl pyrrolidone K30 (PVP K30), and hydroxypropyl cellulose EL (HPC-EF) and citric acid as a pH modulator, while glycerin served as a plasticizer. The sublingual fast-dissolving thin films were characterized by FTIR, SEM, DSC, and XRD and evaluated for in vitro dissolution and ex vivo mucoadhesion. The best formulation (F1) developed using HPMC E15 as a polymer, glycerin as a plasticizer, and citric acid as a pH modulator was found to be the optimized formulation as it was smooth, clear, flexible, and displayed good mucoadhesion (11.27 ± 0.418 gm/cm²) and uniform thickness (0.25 ± 0.02 mm). The formulation F1 was found to display a significantly shorter DT (30.30 ± 0.6 s) and rapid release of LOR (92.10 ± 2.3% in 60 min) compared to other formulations (ANOVA, p < 0.001). The results indicated that the prepared sublingual films are likely to elicit a faster therapeutic effect, avoid first-pass metabolism, and improve the bioavailability. Full article

Sulpiride (Sul) is a medication that blocks dopamine D₂ receptors. It is used to treat gastrointestinal disturbances and has antipsychotic effects depending on the dose given. Sulpiride is subject to P-glycoprotein efflux, resulting in limited bioavailability and erratic absorption. Hence, the aim of this study was to generate a glycerosomal in situ gel of sulpiride for intranasal administration, specifically targeting children with schizophrenia who may have difficulty swallowing traditional solid medications, for enhancing its bioavailability. This study aimed to demonstrate the efficacy of intranasal administration of glycerin-encapsulated lipid-nanovesicles (glycerosomes) mixed with in situ gels for prolonged release of anti-psychotic medication. A Box–Behnken design was utilized to create sulpiride-loaded glycerosomes (Sul-GMs), with the lipid amount (A), glycerin concentration (B), and sonication time (C) acting as independent variables. Their impact on the entrapment efficiency, EE% (Y₁), and in vitro drug release (Y₂) were evaluated. The sulpiride EE% showed an increase when the glycerin concentration was raised to 25% v/v. Nevertheless, when the glycerin concentration was raised to 40% v/v, there was a notable decrease in the EE%. The optimized glycerosome was added to pH triggered carbopol 974P in situ gel formulations including HPMC K15M with different concentrations. The in situ gel formulation (G3) comprising 0.6% carbopol 974P and 0.6% hydroxypropyl methyl cellulose-K15M (HPMC K15M) demonstrated suitable pH, viscosity, desired gel strength, spreadability, and mucoadhesive strength. Consequently, it was selected for in vitro study, ex vivo permeation investigation, and in vivo evaluations. The glycerosomal in situ gel exhibited favorable ex vivo permeability of SU when applied to the nasal mucosa. The pharmacokinetic investigation revealed that the optimized Sul-loaded glycerosomal in situ gel exhibited a significant fourfold and twofold enhancement in systemic bioavailability compared to both the control gel and the commercially available formulation. Finally, the intranasal administration of Sul-loaded glycerosomal in situ gel is a promising alternative to oral treatment for pediatric patients with psychosis. Full article

The combination of nanoemulgel and phytochemistry has resulted in several recent discoveries in the field of topical delivery systems. The present study aimed to prepare nanoemulgel based on turmeric (Curcuma longa) and neem (Azadirachta indica) against microbial infection as topical drug delivery. Olive oil (oil phase), Tween 80 (surfactant), and PEG600 (co-surfactant) were used for the preparation of nanoemulsion. Carbopol 934 was used as a gelling agent to convert the nanoemulsion to nanoemulgel and promote the control of the release of biological properties of turmeric and neem. The nanoemulsion was characterized based on particle size distribution, PDI values, and compatibility using FTIR analysis. In contrast, the nanoemulgel was evaluated based on pH, viscosity, spreadability, plant extract and excipient compatibility or physical state, in vitro study, ex vivo mucoadhesive study, antimicrobial properties, and stability. The resulting nanoemulsion was homogeneous and stable during the centrifugation process, with the smallest droplets and low PDI values. FTIR analysis also confirmed good compatibility and absence of phase separation between the oil substance, surfactant, and co-surfactant with both plant extracts. The improved nanoemulgel also demonstrated a smooth texture, good consistency, good pH, desired viscosity, ex vivo mucoadhesive strength with the highest spreadability, and 18 h in vitro drug release. Additionally, it exhibited better antimicrobial properties against different microbial strains. Stability studies also revealed that the product had good rheological properties and physicochemical state for a period of over 3 months. The present study affirmed that turmeric- and neem-based nanoemulgel is a promising alternative for microbial infection particularly associated with microorganisms via topical application. Full article