Liraglutide (LIRA) is a glucagon-like peptide-1 (GLP-1) receptor agonist renowned for its efficacy in treating type 2 diabetes mellitus (T2DM) and is typically administered via subcutaneous injections. Oral delivery, although more desirable for being painless and potentially enhancing patient adherence, is challenged by the peptide’s low bioavailability and vulnerability to digestive enzymes. This study aimed to develop LIRA-containing zein-based nanoparticles stabilized with eudragit RS100 and chitosan for oral use (Z-ERS-CS/LIRA). These nanoparticles demonstrated a spherical shape, with a mean diameter of 238.6 nm, a polydispersity index of 0.099, a zeta potential of +40.9 mV, and an encapsulation efficiency of 41%. In vitro release studies indicated a prolonged release, with up to 61% of LIRA released over 24 h. Notably, the nanoparticles showed considerable resistance and stability in simulated gastric and intestinal fluids, suggesting protection from pH and enzymatic degradation. Pharmacokinetic analysis revealed that orally administered Z-ERS-CS/LIRA paralleled the pharmacokinetic profile seen with subcutaneously delivered LIRA. Furthermore, in vivo tests on a diabetic rat model showed that Z-ERS-CS/LIRA significantly controlled glucose levels, comparable to the results observed with free LIRA. The findings underscore Z-ERS-CS/LIRA nanoparticles as a promising approach for oral LIRA delivery in T2DM management.

Background/Objectives: Nanoemulsions and microemulsions are promising drug delivery systems capable of enhancing the solubility, stability, and bioavailability of active pharmaceutical ingredients, particularly for central nervous system (CNS) disorders. This study presents a bibliometric analysis of scientific publications on intranasal nanoemulsions from 2004 to 2024, based on data from the Scopus database. Methods: A total of 379 articles were analyzed using Bibliometrix and VOSviewer to identify publication trends, leading countries and institutions, prominent journals, and keyword networks. Results: Publications grew significantly over the last decade, with India, the United States, and China leading in volume. Keyword analysis revealed strong thematic clusters related to “brain targeting,” “drug delivery,” and “intranasal administration,” highlighting this route’s potential for bypassing the blood–brain barrier. The most studied compounds included curcumin, quercetin, carbamazepine, diazepam, and insulin, each with therapeutic applications in neurodegenerative and psychiatric disorders. Conclusions: The findings highlight growing interest in intranasal nano- and microemulsions as a non-invasive and efficient CNS delivery strategy. Future research can bridge translational gaps, enhancing efficacy and safety while meeting regulatory expectations for patient-centered drug development. This study provides a comprehensive overview of current trends and serves as a guide for advancing innovative intranasal delivery platforms.

Background: Silibinin (SLB), a flavonoid derived from milk thistle, exhibits promising therapeutic properties but faces significant clinical limitations due to poor solubility and bioavailability. Objectives: This study focuses on the development and characterization of SLB-loaded nanoemulsions designed for mucosal delivery. Methods: Nanoemulsions were prepared using the spontaneous emulsification method, guided by pseudoternary phase diagrams to determine selected component ratios. Comprehensive characterization included particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, rheological properties, and surface tension. Mucoadhesive properties were evaluated using quartz crystal microbalance with dissipation (QCM-D) to quantify interactions with mucin layers. Results: The combination of Capryol 90, Tween 80, and Transcutol in selected proportions yielded nanoemulsions with excellent stability and solubilization capacity, enhancing the solubility of silibinin by 625 times compared to its intrinsic solubility in water. The ternary phase diagram indicated that achieving nanoemulsions with particle sizes between 100 and 300 nm required higher concentrations of surfactants (60%), relative to oil (20%) and water (20%), with formulations predominantly composed of Smix (surfactant and cosurfactant mixture in a 1:1 ratio). Rheological analysis revealed Newtonian behavior, characterized by constant viscosity across varying shear rates and a linear torque response, ensuring ease of application and mechanical stability. QCM-D analysis confirmed strong mucoadhesive interactions, with significant frequency and dissipation shifts, indicative of prolonged retention and enhanced mucosal drug delivery. Furthermore, contact angle measurements showed a marked reduction in surface tension upon interaction with mucin, with the SLB-loaded nanoemulsion demonstrating superior wettability and strong mucoadhesive potential. Conclusions: These findings underscore the suitability of SLB-loaded nanoemulsions as a robust platform for effective mucosal drug delivery, addressing solubility and bioavailability challenges while enabling prolonged retention and controlled therapeutic release.

Zein-based nanoparticles offer significant potential as carriers for drug delivery due to their biocompatibility. However, optimizing their formulation is essential to achieving efficient encapsulation and stability. This study aimed to optimize the formulation of zein-casein-hyaluronic acid-based nanoparticles for the encapsulation of a hydrophilic drug, focusing on achieving favorable physicochemical properties for oral drug delivery applications. A factorial experimental design was employed to evaluate the influence of key formulation parameters, including zein concentration, hyaluronic acid concentration, sodium caseinate concentration, and the organic-to-aqueous phase (O/W) ratio. Particle size (PS), polydispersity index (PDI), zeta potential, and encapsulation efficiency (EE) were analyzed as response variables. Multivariate analyses, such as hierarchical cluster analysis and principal component analysis, were performed to explore the relationships between formulation parameters and nanoparticle properties. Model validity was confirmed by using ANOVA and residual analysis. Optimized nanoparticles exhibited a PS of 217 ± 5 nm, PDI of 0.077 ± 0.022, zeta potential of -24.7 ± 1.9 mV, and EE of 31% ± 4. The nanoparticles displayed a monomodal size distribution and a spherical morphology. Multivariate analyses revealed that the O/W ratio and zein concentration were the most influential factors, while sodium caseinate played a crucial stabilizing role. The desirability function yielded a high score (D = 0.9338), confirming the robustness of the optimization process. Stability studies demonstrated that refrigeration at 8 °C preserved the nanoparticles' physicochemical properties over 180 days. This study underscores the power of experimental design as a tool to refine nanoparticle formulations, paving the way for more efficient drug delivery systems and unlocking new possibilities for the oral administration of hydrophilic compounds.

Glioblastoma, an aggressive intracranial tumor, presents significant therapeutic challenges due to the restrictive nature of the blood-brain barrier (BBB), which limits the effectiveness of conventional treatments. This study aimed to develop and optimize a nanoencapsulated system for intranasal delivery of temozolomide (TMZ) and perillyl alcohol (POH), designed to circumvent BBB limitations, utilizing Eudragit RS100 as the encapsulation matrix. A factorial design approach optimized key parameters, including Eudragit RS100 concentration, POH amount, drip rate, and organic-to-aqueous phase ratio. The nanocapsules were characterized by dynamic light scattering, zeta potential analysis, scanning electron microscopy, and high-performance liquid chromatography. The optimized nanocapsules demonstrated a mean diameter of 253 ± 52 nm and a polydispersity index of 0.145 ± 0.037, indicating uniform size distribution. A zeta potential of approximately +20 mV supported colloidal stability. Encapsulation efficiencies were 3.7% for POH and 28.5% for TMZ. This nanoencapsulated delivery system offers a promising approach for glioblastoma treatment, potentially enhancing clinical outcomes and reducing treatment-associated toxicity.