Objectives

The objective of this study is to develop a mebendazole (MBZ) nanosuspension designed as an immediate-release dosage form to improve solubility and bioavailability.

Material and Methods

MBZ, classified as a BCS Class II drug, demonstrates low bioavailability (<10%) due to its limited solubility (0.035 mg/mL). The wet-media milling technique was utilised to reduce particle size, which subsequently increased surface area and dissolution rate. Polyvinyl alcohol (PVA) has been chosen as the stabiliser to improve formulation stability and inhibit particle aggregation. A comprehensive factorial design was employed to optimise critical process parameters, resulting in a nanosuspension characterised by an optimized mean particle size and a polydispersity index (PDI).

Results:

The optimised formulation exhibited an 8.72-fold enhancement in solubility and achieved over 98% drug release within 60 minutes in vitro, markedly surpassing both pure MBZ and existing marketed formulations. The formulation demonstrated a high entrapment efficiency of 96.21% and a drug content of 97.53%, thereby ensuring optimal drug loading. The successful conversion of MBZ into the amorphous form was confirmed through differential scanning calorimetry (DSC). The freeze-drying process enhanced dissolution properties while preserving formulation integrity, stability, and long-term viability. The solubility of the nanosuspension exhibited a significant increase in both aqueous and acidic media, effectively addressing the dissolution-limited absorption of MBZ.

Conclusions:

The findings indicate that nanosuspension technology represents a viable approach for enhancing the dissolution of poorly soluble drugs. The research highlights the potential use of nanosuspensions in drug delivery, especially for BCS Class II compounds, providing an effective formulation strategy to improve pharmacokinetic performance, stability, safety, and therapeutic results.

Hepatic encephalopathy (HE) is a severe neurological complication of liver failure with limited therapeutic options. Vardenafil dihydrochloride (VD), a PDE5 inhibitor, used for erectile dysfunction, shows potential for HE prophylaxis through cGMP elevation and neuroprotection, but it suffers poor oral bioavailability due to low solubility and first-pass metabolism. This study aimed to develop hybrid lipid-polymeric nanoparticles (HLPNPs) with piperine as a bioavailability enhancer for VD repurposing in HE prevention.

HLPNPs were prepared using homogenization/ultrasonication technique with glyceryl tripalmitate and Eudragit RS100. The helper polymer type (oleic acid, chitosan, sodium alginate) was evaluated using a one-factor experimental design on each of the particle size, polydispersity index, zeta potential, and entrapment efficiency. In vitro release studies, pharmacokinetics and therapeutic efficacy tests in a thioacetamide-induced HE mouse model were conducted.

Oleic acid emerged as the optimal helper polymer, yielding HLPNPs with 128±2.8 nm particle size, 0.173±0.07 PDI, -32±1.67 mV zeta potential, and 93±1.8% entrapment efficiency. In vitro release showed sustained VD release (~70% over 72h) following Korsmeyer-Peppas kinetics. Pharmacokinetic studies revealed a remarkable 9-fold improvement for the optimized formulation compared to standard VD, with C_max increasing from 9 ng/mL to 22 ng/mL. In the HE mouse model, the optimized formulation significantly improved liver enzymes (ALT, AST), reduced ammonia levels, and enhanced hippocampal BDNF, cGMP, GluR1, and P-CREB levels compared to standard VD treatment.

The piperine-enhanced HLPNPs successfully overcame VD's bioavailability limitations and demonstrated superior therapeutic efficacy in HE prevention. This innovative drug repurposing approach combining nanotechnology with bioavailability enhancement offers a promising strategy for expanding VD's therapeutic applications beyond erectile dysfunction to neurological conditions.

This study investigates graphene oxide (GO) dispersions in dimethyl sulfoxide (DMSO) as an intermediate platform for developing nanocarriers for biomedical applications. DMSO's high polarity and hydrogen bonding ability make it an effective medium for optimizing GO's dispersion and optical properties before transferring to biocompatible systems.

GO was synthesized from glucose, and dispersions in DMSO (0.125–1.5 g/L) were prepared using mechanical stirring and ultrasonic homogenization. UV-Vis-NIR spectroscopy (200–3000 nm) was used to characterize the dispersions. Key parameters like transmittance, absorption coefficients, and bandgap width were calculated.

Controlled ultrasonic treatment produced stable dispersions with an increased molar extinction coefficient (εm ≈ 14 l·g⁻¹·cm⁻¹), indicating effective exfoliation and a rise in sp² domains. The constant optical bandgap (Eg ≈ 3.95–4.0 eV) confirmed the process was non-destructive, preserving GO's functional integrity. Spectroscopic data revealed specific GO-DMSO interactions, such as hydrogen bonding, which ensure colloidal stability.

The established dispersion patterns and spectral behaviors in DMSO can be translated to biocompatible media like aqueous buffers or amphiphilic polymers (e.g., Pluronic F127), maintaining the material's stability and optical properties. This protocol provides a universal platform for preparing GO dispersions suitable for drug delivery systems, contrast agents, and optical biosensors. The original contribution demonstrates that DMSO as an intermediate enables controlled GO dispersion and the formation of optical parameters reproducible in pharmaceutical systems.

Introduction: Carbon Dots (CDs) have emerged as promising nanomaterials for pharmaceutical and diagnostic applications due to their tunable fluorescence, biocompatibility, and potential for surface functionalization. Their dual applicability as drug delivery nanocarriers and fluorescent probes for bioimaging makes their physicochemical characterization crucial for advancing biomedical research. Methods: CDs were synthesized using citric acid as the carbon precursor through two distinct approaches: thermal pyrolysis in an oil bath at 200 °C for 30 min and a hydrothermal method at 200 °C for 4 h in the presence of urea as a nitrogen source. The nanostructures were characterized by transmission electron microscopy (TEM), UV-Vis absorption spectroscopy, photoluminescence spectroscopy, Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, and zeta potential analysis. Results: TEM analysis revealed spherical and homogeneous particles with an average diameter of 3.0–3.5 nm, consistent with the size range of quantum dots. Optical characterization showed stable photoluminescence, with absorption maxima at 333–350 nm and excitation-independent emission attributed to ordered sp² domains. Nitrogen doping significantly enhanced fluorescence intensity, increasing quantum yield and improving stability within a physiological pH range (4.5–9.5). FTIR spectra confirmed the presence of surface functional groups such as C=O, C–N, and C–OH, while Raman analysis revealed the characteristic D and G bands of graphitic carbon. Zeta potential values of approximately –30 mV indicated high colloidal stability and abundant anionic groups favorable for further functionalization. Conclusions: The combination of small size (<10 nm), high photostability, tunable fluorescence, and negative surface charge highlights the multifunctional potential of CDs. These features support their application both as drug delivery systems, responsive to physiological conditions, and as fluorescent probes for bioimaging, reinforcing their relevance as advanced platforms in therapeutic and diagnostic contexts.

Introduction: Silver nanoparticles are well known for their antibacterial, antiviral, and antifungal properties. Although the exact mechanism is not fully understood, it is believed to be strongly related to the release of Ag+ ions, which contribute to cell death. Polymers can interact with the cell surface, potentially enhancing ion release and increasing the antimicrobial effect. In this study, we used biocompatible polymers in a seed-mediated growth method to produce silver nanospheres and evaluate their activity against Candida albicans. Methodology: Candida albicans was cultured on Sabouraud Agar and standardized to 10⁶ CFU/mL. Silver nanospheres were synthesized using Carbopol® 940 (CBP), Alginate (Alg), and Sodium Poly-4-Styrene-Sulfonate (PSS), then purified by centrifugation prior to use in the experiments. The nanospheres were incubated with fungal cells for 24 hours. After incubation, each test sample was serially diluted from 10⁻¹ to 10⁻⁴, and 10 µL of each dilution was plated on Sabouraud Agar. Results and discussion: Our findings showed that AgNP-PSS resulted in the greatest reduction in fungal activity, with a 4 Log₁₀ reduction, compared to AgNP-CBP (2.7 Log₁₀) and AgNP-Alg (1.7 Log₁₀). We believe this enhanced effect may be related to the presence of sulfur groups in the PSS molecules. Conclusion: AgNPs exhibited the expected antifungal activity against Candida albicans in vitro, and the results with PSS suggest that polymer interactions play a key role in mediating their mechanism of action.

Introduction: Gene therapy holds immense therapeutic potential, but its efficacy relies on safe and efficient gene delivery systems. Non-viral vectors, such as polyethylenimine (PEI), offer advantages over viral methods, including lower immunogenicity and easier fabrication. The primary challenge of non-viral gene delivery vectors lies in their lower transfection efficiency compared to viral systems. This study investigates novel PEI-based ternary complexes utilizing anionic peptides to enhance plasmid DNA delivery by mitigating the significant cytotoxicity and non-specific interactions associated with cationic vectors.

Methods: We developed ternary polyelectrolyte complexes comprising plasmid DNA, PEI, and anionic, glutamate-rich peptides (E6p, cRGD-E6p, E6Hp, E6p0), which varied in their histidine content and the presence of an αvβ3 integrin-targeting ligand (cRGD). Their transfection efficiency was evaluated in vitro using PANC-1 cells and in vivo via intramuscular injection in m. quadriceps f. in mice. Reporter genes (lacZ and GFP) were used to quantify efficiency of delivery through β-galactosidase assays and fluorescence microscopy.

Results: Optimal charge (Phosphorus/Nitrogen/Carboxyl) ratios for high transfection efficiency were identified. For the E6p0 peptide, the most effective DNA/PEI/peptide ratio was 1/16/2, while for E6p, cRGD-E6p, and E6Hp, it was 1/16/4. Reducing the injection volume to two-fold did not compromise transfection efficiency but minimized tissue damage in vivo. All formulations achieved statistically significant transfection levels compared to the control group. Peptides E6p0 and E6p showed the highest performance in vivo, evidenced by a greater number of GFP-positive muscle fibers.

Conclusion: The designed ternary complexes exhibit high efficacy for plasmid DNA delivery both in vitro and in vivo, highlighting their strong potential as versatile vectors for therapeutic gene delivery applications.

Introduction: Benznidazole (BNZ), a poorly water-soluble drug, is the first-line treatment for Chagas disease; however, long treatment periods at high doses often cause adverse effects with insufficient efficacy in the chronic phase. This study aimed to design and compare benznidazole-loaded nanoparticles (NPs) and lipid nanocapsules (LNCs) with the pure drug, focusing on dissolution enhancement and kinetic modeling to support strategies for improving oral bioavailability.

Methods: LNCs were prepared by the phase inversion technique, yielding formulations with an average diameter of 50 nm, an encapsulation efficiency between 83–92%, and drug loading between 0.66–1.04%. NPs were obtained by the liquid anti-solvent precipitation process, also with diameters of approximately 50 nm. Both systems were evaluated and compared with the pure drug by in vitro release assays in simulated gastric medium at 37 °C. The experimental data were fitted to the Lumped-Gonzo model, which provided pharmaceutically relevant parameters and showed an excellent fit to the release profiles (R² > 0.99).

Results: The pure drug exhibited very limited dissolution, requiring more than 280 minutes to reach 20% release (t_20%) and showing a mean dissolution time (MDT_20%) close to 90 minutes. In contrast, LNCs doubled the initial release rate compared with BNZ, reduced MDT_20% to around 33 minutes, and increased dissolution efficiency (DE_360min) to 26.3%. NPs showed the most remarkable performance, achieving a very fast initial release rate of 1.5701 %/min and a maximum release of 89.2%.

Conclusions: Both formulations enhanced benznidazole dissolution compared with the pure drug, with LNCs showing a moderate but sustained effect and NPs achieving the most pronounced improvement. These findings highlight the potential of nanocarriers, particularly NPs, as promising platforms for improving BNZ oral bioavailability.

Introduction: The development of efficient drug delivery systems remains a major challenge in pharmaceutical sciences. Nanomaterials, thanks to their exceptional properties, are fundamental to advancements in this field. Among them, lipid-based nanocarriers—such as solid lipid nanoparticles (SLN) and lipid nanocapsules (LNC)—stand out for their ability to encapsulate both hydrophilic and lipophilic drugs, improving solubility and stability, and enabling targeted or controlled release. Ciprofloxacin was used as a model drug in dissolution studies due to its well-documented properties. This study aimed to design and optimize lipid nanocarriers (SLN and LNC) for oral ciprofloxacin delivery, evaluating their stability and release profiles through predictive kinetic modeling to enhance bioavailability and support the rational development of nanomedicines.

Methods: SLN were synthesized using Gelucire 44/14, Span 80, and Tween 80, while LNC were prepared with Kolliphor, soybean lecithin, and Labrafac. Transmission electron microscopy confirmed that both nanocarriers exhibited spherical morphology with an approximate diameter of 50 nm.

Results: Encapsulation efficiencies were 97.9% and 98.0% for SLN and LNC, respectively. Stability studies over two months revealed that LNC remained stable at both 4°C and 25°C, whereas SLN experienced notable particle size changes after 7 days at 25°C. Release profiles in simulated gastric fluid were successfully fitted using the Lumped–Gonzo kinetic model, yielding high correlation coefficients (R² = 0.9980 and 0.9886 for LNC and SLN, respectively).

Conclusions: These results demonstrate that predictive kinetic modeling is a valuable strategy for guiding the rational design of stable and effective lipid-based nanocarriers to improve ciprofloxacin oral bioavailability.

Hemangioma is an abnormal growth of blood vessels in the skin, forming a benign tumor, mostly common in infants and children. Propranolol (PRO) is a non-selective beta-blocker used as an antihypertensive that has shown regression in infantile hemangiomas. Its oral administration comes with adverse effects, including a high risk for asthmatic patients, and only 25% of the administered dose is bioavailable. With that in mind, the incorporation of PRO into nanocapsules (NCs)-based polymeric films provides protection against degradation, prolongs its half-life, allows controlled release, and modulates its skin permeation/penetration. Given the above, this study incorporates propranolol Eudragit RL®100 nanocapsules in pectin films, obtained by the solvent casting method, and characterizes them for porosity and intumescence. Nanocapsules presented 151 ± 7.86 nm, 0.134 ± 0.01 PDI, and 25.64 ± 4.9 zeta potential. The pectin films (1%) were homogeneous and transparent. The porosity ratio was determined by the amount of absorbed solvent by the film sample after immersion in ethanol. Samples were obtained from vehicle formulation, free drug, NC-PROP, and blank NC films. The results obtained after 24h were 55.93 ± 3.13%, 49.91 ± 0.56%, 42.49 ± 2.05%, 41.74 ± 2.5%, respectively. This indicates that the NCs interact in a way that modifies the pores and creates a more effective barrier than the vehicle or free drug form. For intuminescence, the same method was applied, apart from the solvent being a pH 7.4 buffer, but all the film samples disintegrated and dissolved in the buffer, indicating a biodegradable matrix. The incorporation of PRO-loaded nanocapsules into pectin films resulted in homogeneous and biodegradable matrices with reduced porosity and promising barrier properties. These characteristics suggest that NC-PROP films can provide a controlled and localized drug release, potentially reducing systemic adverse effects associated with oral administration. Overall, this approach represents a promising strategy for the topical treatment of infantile hemangiomas.

Oxidative stress is a pathological condition that plays crucial roles in the pathogenesis of various diseases. This study evaluated the antioxidant and toxicological effects of verbenone enhanced with cyclodextrin and lysine in diclofenac induced oxidative stress mice. Adult Swiss mice (35) were randomly distributed into seven (7) groups, induced with oxidative stress and orally administered verbenone, lysine, cyclodextrin, verbenone-lysine, and verbenone-cyclodextrin at 200 mg/kg body weight for seven (7) days. Cyclodextrin treatment significantly increased (p<0.05) total cholesterol, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglycerides compared with diclofenac control. No significant alterations (p<0.05) were observed in very low density lipoprotein cholesterol (VLDL), while a significant increase (p<0.05) was observed with diclofenac treatment in liver triglycerides. No significant alterations (p<0.05) were observed with atherogenic index while cyclodextrin significantly increased cardiac index and coronary artery index. Plasma protein and catalase activities decreased significantly (p<0.05) in all treatment groups. No significant alterations (p<0.05) were observed in malondialdehyde and liver superoxide dismutase. Glutathione peroxidase activity decreased in plasma for verbenone, cyclodextrin, and verb-cyclodextrin, but increased in the liver with lysine and cyclodextrin treatments. Liver albumin and total bilirubin were elevated in treatments, while gamma-glutamyl transferase activity significantly increased (p<0.05) across all groups except with verbenone treatment. Histopathology revealed periportal inflammation in verb-lysine, and while liver and kidney architecture in verb-cyclodextrin and verbenone groups was preserved. The study reveals complex interactions between diclofenac-induced oxidative stress and the modulatory effects of verbenone, lysine, and cyclodextrin. Verbenone and the various mitigated oxidative damage, with cyclodextrin conjugation presented more safety profile compared to lysine conjugation. The combination of verbenone and lysine or cyclodextrin may provide valuable insights into the modulation of renal and hepatic functions under oxidative stress conditions.