High Entrapment Efficiency Research Articles

Isoquercitrin Loaded PEGylated Long Circulating Liposomes Improve Bone Mass and Reduce Oxidative Stress After Osteoporosis.

Osteoporosis has increasingly become a major public health concern because of its associated heightened risk of bone fragility and fractures. In order to avoid the adverse risk of hormone therapy, scientists have considered isoquercitrin (IQ) as a natural phytoestrogen to potentially prevent osteoporosis. However, IQ has poor solubility and bioavailability which culminates in rapid elimination of phytoestrogen. Herein, this study sought to solve limited applications of IQ by preparing IQ-loaded PEGylated long circulating liposomes (IQ-Lips) via thin-film hydration method. After appropriate characterization using zeta-potential, polydispersed index (PDI), particle size and entrapment efficiency (EE), IQ-Lips were applied to ovariectomized rat models to evaluate their effect on osteoporosis. The results showed that the prepared IQ-Lips exhibited smaller sized nanoparticles (125.35 ± 4.50nm), excellent PDI (0.244 ± 0.001) and zeta-potential (-28.64 ± 0.71 mV) with stable property and higher EE (92.10 ± 0.32%). Importantly, administration of IQ-Lips through oral route increased aqueous solvability, bioavailability and circulation time of IQ. Moreover, the IQ-Lips could increase bone microstructural densities and bone mass, as well as reduce oxidative stress in ovariectomized rat models. Altogether, the IQ-Lips may serve as a novel avenue to potentially prolong the circulation of IQ in the body and improve the bioavailability of IQ for treatment of osteoporosis.

Investigation of Spray Drying Parameters to Formulate Novel Spray-Dried Proliposome Powder Formulations Followed by Their Aerosolization Performance

Background: Spray drying, whilst a popularly employed technique for powder formulations, has limited applications for large-scale proliposome manufacture. Objectives: Thus, the aim of this study was to investigate spray drying parameters, such as inlet temperature (80, 120, 160, and 200 °C), airflow rate (357, 473, and 601 L/h) and pump feed rate (5, 15, and 25%), for individual carbohydrate carriers (trehalose, lactose monohydrate (LMH), and mannitol) for 24 spray-dried (SD) formulations (F1–F24). Methods: Following optimization, the SD parameters were trialed on proliposome formulations based on the same carriers and named as spray-dried proliposome (SDP) formulations. Drug delivery of the formulations was assessed using a dry powder inhaler (DPI) in combination with a next-generation impactor (NGI). Results: Upon analysis, formulations F6 (SD-mannitol), F15 (SD-trehalose), and F20 (SD-LMH) demonstrated high production yields (84.01 ± 3.25, 72.55 ± 5.42, and 70.03 ± 3.39%, respectively), small particle sizes (2.96 ± 1.42, 4.55 ± 0.46, and 5.16 ± 1.32 µm, respectively) and low moisture contents (0.25 ± 0.03, 3.76 ± 0.75, and 1.99 ± 0.77%). These SD optimized parameters were then employed for SDP formulations employing dimyristoly phosphatidylcholine (DMPC) as a phospholipid and beclomethasone dipropionate (BDP) as the model drug. Upon spray drying, SDP-mannitol provided the highest production yield (82.45%) and smallest particle size (2.64 µm), as well as high entrapment efficiency (98%) and a high fine particle dose, fine particle fraction, and respirable fraction (285.81 µg, 56.84%, 86.44%, respectively). Conclusions: The study results are a promising step in the optimization of the large-scale manufacture of proliposome formulations and highlight the versatility of the instrument and variability of formulation properties with respect to the carriers employed for targeting the pulmonary system using dry powder inhalers.

Design of solid lipid nanoparticles for skin photoprotection through the topical delivery of caffeic acid-phthalimide

Exposure of the skin to ultraviolet (UV) radiation is associated with many pathological conditions such as premature aging and skin cancer. Furthermore, members of Nicotinamide Adenine Dinucleotide Phosphate-oxidase (NADPH oxidase or NOX) enzyme family can produce UV-induced reactive oxygen species (ROS), even after cessation of radiation exposure. The caffeic acid-phthalimide (CF) compound is a potent antioxidant, which reduces the generation of ROS. However, its high lipophilicity may hamper its permeation through the skin. Solid lipid nanoparticles (SLNs) can ensure close contact and increase the amount of drug absorbed into the skin. The present work aims to develop and optimize SLNs containing CF to achieve enhanced skin photoprotection along with antioxidant and anti-aging effects. SLNs were prepared by the hot homogenization method using Compritol 888 ATO as the lipid matrix, and Tween 80 and Pluronic® F-127 as the surfactants to stabilize nanoparticle dispersion. The particles had high stability for at least 30 days. Physicochemical characterizations of the selected SLNs formulations showed sizes in the range 150–180 nm, polydispersity index (PDI) of 0.2, and a negative zeta potential (≅ −25 mV). The SLNs had high CF entrapment efficiency (96–97 %) and showed a controlled drug‐release profile. The in vitro study revealed low cytotoxic properties of CF-loaded SLNs towards fibroblasts and a photoprotective effect, reflected from the increased viability of UVB-irradiated fibroblasts treated with CF-SLNs. Moreover, the CF-SLNs induced fibroblast migration and closure, showing that these nanosystems offer not only biological photoprotection, but also stimulate wound healing.

A LIPOSOMAL CONTROLLED DELIVERY SYSTEM FOR PLANTAGO MAJOR L. EXTRACTS AND THEIR BIOLOGICAL ACTIVITY FOR WOUND HEALING

The objectives of this study are to determine the effective features of water and aqueous-ethanol extracts of Plantago major L. (Pm-dH2O and Pm-EtOH, respectively) in wound healing, such as antimicrobial, antioxidant potential, and fibroblast proliferation. Furthermore, it was targeted to obtain liposome structures loaded with Pm-extract for controlled release, characterize the obtained liposomes, and determine their release profiles. Antimicrobial activity (inhibition zone and minimum inhibition concentration), total antioxidant and oxidant (TAS, TOS, and OSI) potentials, total phenolic content (TPC), and total flavonoid content (TFC) of Pm extracts were tested. The radical scavenging activity of Pm extracts was quantified by the DPPH assay. Antioxidant capabilities of Pm extracts were determined with ABTS, CUPRAC, and FRAP. In vitro cytotoxicity tests of Pm extracts were examined on dermal fibroblast cells with MTT assay. Liposome structures loaded with Pm extracts were obtained using the ethanol injection method. Plant extract-loaded liposomes were characterized, and in vitro release kinetics were revealed by dialysis technique. Pm-EtOH extract inhibited the growth of microorganisms at lower concentrations than Pm-dH2O extract. According to TAS, TOS, and OSI values, it was concluded that there was a moderate antioxidant effect in Pm extracts in general. TPC and TFC of the Pm-EtOH extract are higher than the Pm-dH2O extract. Inhibition percentages of Pm-EtOH extract are higher than Pm-dH2O extracts against DPPH free radicals. The ABTS, CUPRAC, and FRAP antioxidant capacities of the Pm-EtOH extract are higher than that of the Pm-dH2O extract. Furthermore, according to dynamic light scattering and microscopy images, these plant extracts loaded liposomes had a high entrapment efficiency, a wide size range, and good stability. Pm extracts showed high cell viability and no cytotoxic effect on HDF cells. Liposome structures loaded with Pm extracts are fine alternatives for effective and controlled release to the wound site due to high entrapment efficiency, a wide size range, and good stability.

Biotinylated platinum(IV)-conjugated graphene oxide nanoparticles for targeted chemo-photothermal combination therapy in breast cancer

Graphene oxide (GO) and GO-based nanocomposites are promising in drug delivery and photothermal therapy due to their exceptional near-infrared optical absorption and high specific surface area. In this study, we have effectively conjugated an oxaliplatin (IV) prodrug, PEGylated graphene oxide, and PEGylated biotin (PB) in a single platform for breast cancer treatment. This platform demonstrates promising prospects for targeted drug delivery and the synergistic application of photothermal-chemotherapy when exposed to NIR-laser irradiation. The resulting nanocomposite (GO(OX)PB (1/1/0.2) NPs) displayed an exceptionally large surface area, minimal particle size (195.7 nm), specific targeting capabilities, a high drug load capacity (43.56 %) and entrapment efficiency (89.48 %) and exhibit excellent photothermal conversion efficiency and photostability when exposed to NIR-laser irradiation (808 nm). The therapeutic effectiveness was assessed both in vitro and in vivo conditions employing human breast cancer cells (MCF-7), mouse mammary gland adenocarcinoma cells (4T1), and 4T1-Luc tumor-bearing mouse models. The findings demonstrated that GO(OX)PB (1/1/0.2) NPs (+L) were highly effective in causing significant cytotoxicity, G2/M phase cell cycle arrest, ROS generation, mitochondrial membrane depolarization, apoptosis, and photothermal effect. This resulted in a greater percentage of cell death compared to free OX, GO(OX)PEG (1/1/0.2) NPs (±L), and GO(OX)PB (1/1/0.2) NPs (−L). The in vivo therapeutic studies on 4T1-Luc tumor-bearing mice revealed that a combination of GO(OX)PB (1/1/0.2) NPs (+L) caused complete disappearance of the tumor, no tumor recurrence, prolonged survival, reduced lung metastasis, and mitigated nephrotoxicity. The serum and blood analysis demonstrated minimal systemic toxicity of GO(OX)PB (1/1/0.2) NPs. The developed nanoplatform, in this context, may serve as a potential nanomedicine to address conventional nephrotoxicity in breast cancer and prevent metastasis by combining chemo-photothermal therapy.

Comparative Study of pH-Responsive and Aggregation Stability of Bosutinib-Loaded Nanogels Comprising Gelatin Methacryloyl, Carboxymethyl Dextran, and Hyaluronic Acid for Controlled Drug Delivery in Colorectal Cancer: An Extensive In Vitro Investigation.

This study investigates the use of pH-responsive nanogels for delivering Bosutinib (BOSU) in colon cancer treatment. Nanogels were formulated using three polymers: hyaluronic acid (HA), carboxymethyl dextran (CMD), and gelatin methacryloyl (GelMA). These nanogels achieved high drug entrapment efficiencies (80-90%) through polymer mixing with BOSU, followed by EDC/NHS cross-linking and sonication. The nanogels were stable, with negative zeta potentials (-20 to -30 mV) and particle sizes between 100 and 200 nm. Fourier-transform infrared analysis confirmed successful methacrylation in GelMA nanogels. Sustained BOSU release at pH 5.0 was observed, resembling tumor environments, compared to slower release at normal pH (7.4). Cytotoxicity tests showed 70-80% cell survival reduction in HCT116 colon cancer cells at higher doses, and GelMA-BOSU nanogels notably reduced cell migration. Antiangiogenic effects were confirmed in a chick chorioallantoic membrane model, highlighting the potential of these nanogels for targeted BOSU delivery in colon cancer therapy.

Fabrication and Evaluation of Polyacrylate Nanocomposites Embedded With Metal Oxides as Enhanced Multipurpose Nanocarriers for Long‐Term Anti‐Inflammatory and Amazing Antimicrobial Properties

ABSTRACTThe design of super‐antimicrobially active multipurpose nanocarriers as polymeric nanocomposites embedded with metal oxides with sustained drug release is beneficial in medical treatment for controlling inflammation and targeting a wide range of pathogenic microorganisms. Brilliant metal oxide nanoparticles (MOx) involving selenium dioxide, titanium dioxide, and vanadium pentoxide were well prepared in good yields, and their morphologies and structures were specified. Then they were embedded in copolymeric nanocomposites through in situ microemulsion polymerization of (E)‐2‐cyano‐N‐cyclohexyl‐3‐(dimethylamino)acrylamide (CHAA) with methyl methacrylate (MMA), dimethylaminoethyl methacrylate (DMAEMA), and acrylic acid (AA). In addition, ibuprofen was then loaded into the synthesized polymers and their nanocomposites to achieve high drug entrapment efficiency EE%, and its release behavior was studied in various simulated fluids. The produced drug‐loaded polymers and their nanocomposites were characterized using Fourier‐transform infrared spectroscopy (FT‐IR), transmission electron microscope (TEM), X‐ray diffraction (XRD), and thermogravimetric analysis (TG). Well‐defined nanospheres of polymeric‐metal oxide nanocomposites were generated in a size range of 50 nm, with ibuprofen loaded at a high encapsulation efficiency of approximately 97%. In vitro drug release was inspected for the polymer and its nanocomposites revealing that the presence of metal oxide nanoparticles resulted in prolonged and sustained release behavior for wound dressing. The antimicrobial study based on the zone of inhibition against various pathogenic microorganisms showed excellent activity against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Helicobacter pylori, and Candida albicans. These findings validate the potential of these nanocomposites to serve as a viable upcoming antimicrobial agent for the treatment of human ailments.

Development, optimization, and characterization of polymeric micelles to improve dasatinib oral bioavailability: Hep G2 cell cytotoxicity and in vivo pharmacokinetics for targeted liver cancer therapy

The efficacy of dasatinib (DAS) in treating hepatocellular carcinoma (HCC) is hindered by its poor bioavailability, limiting its clinical potential. In this study, we explored the use of TPGS-Soluplus micelles as an innovative drug delivery platform to enhance DAS solubility, stability, and therapeutic impact. A series of TPGS-Soluplus copolymers were synthesized, varying the D-α-tocopheryl polyethylene glycol succinate (TPGS) forms (1000, 2000, and 3500) and adjusting the TPGS to Soluplus weight ratios (1:1, 1:2, and 1:3). Our goal was to identify the optimal formulation with the highest entrapment efficiency, smallest particle size, and enhanced drug loading. The TPGS1000-Soluplus copolymer, with a DAS-to-polymer ratio of 1:30 and a TPGS ratio of 1:2, demonstrated superior performance, achieving an entrapment efficiency of 64.479 ± 1.45 % and drug loading of 5.05 ± 1.01 %. The DAS-loaded micelles (DAS-PMs) exhibited a notably small particle size of 64.479 ± 1.45 nm and demonstrated controlled release kinetics, with 85.60 ± 5.4 % of the drug released over 72 h.Cellular uptake studies using Hep G2 cells revealed significantly enhanced absorption of DAS-PMs compared to free DAS, reflected in lower IC50 values in MTT assays at 24 and 48 h. Pharmacokinetic analysis further highlighted the benefits of the DAS-PMs, with an AUC0-∞ 2.16 times higher and mean residual time (MRT) 1.3 times longer than free DAS, a statistically significant improvement (p < 0.01). These findings suggest that TPGS-Soluplus micelles offer a promising strategy for improving the bioavailability and efficacy of DAS in HCC treatment, presenting a potential new therapeutic avenue for patients with limited options. This innovative formulation could significantly enhance DAS delivery, potentially leading to improved clinical outcomes in liver cancer therapy.

Development of a selective COX-2 inhibitor: from synthesis to enhanced efficacy via nano-formulation.

Non-steroidal anti-inflammatory drugs NSAIDs are widely used for managing various conditions including pain, inflammation, arthritis and many musculoskeletal disorders. NSAIDs exert their biological effects by inhibiting the cyclooxygenase (COX) enzyme, which has two main isoforms COX-1 and COX-2. The COX-2 isoform is believed to be directly related to inflammation. Based on structure-activity relationship (SAR) studies of known selective COX-2 inhibitors, our aim is to design and synthesize a novel series of 2-benzamido-N-(4-substituted phenyl)thiophene-3-carboxamide derivatives. These derivatives are intended to be selective COX-2 inhibitors through structural modification of diclofenac and celecoxib. The compound 2-benzamido-5-ethyl-N-(4-fluorophenyl)thiophene-3-carboxamide VIIa demonstrated selective COX-2 inhibition with an IC50 value of 0.29 μM and a selectivity index 67.24. This is compared to celecoxib, which has an IC50 value of 0.42 μM and a selectivity index 33.8. Molecular docking studies for compound VIIa displayed high binding affinity toward COX-2. Additionally, the suppression of protein denaturation with respect to albumin was performed as an indicative measure of the potential anti-inflammatory efficacy of the novel compounds. Compound VIIa showed potent anti-inflammatory activity with 93% inhibition and an IC50 value 0.54 μM. In comparison, celecoxib achieved 94% inhibition with an IC50 value 0.89 μM. Although molecule VIIa demonstrated significant in vitro anti-inflammatory activity, adhered to Lipinski's "five rules" (RO5) and exhibited promising drug-like properties, it showed indications of poor in vivo activity. This limitation is likely due to poor aqueous solubility, which impacts its bioavailability. This issue could be addressed by incorporating the drug in niosomal nanocarrier. Niosomes were prepared using the thin-film hydration technique. These niosomes exhibited a particle size of less than 200 nm, high entrapment efficiency, and an appropriate drug loading percentage. Transmission electron microscopy (TEM) and differential scanning calorimetry (DSC) studies revealed that the niosomes were spherical and demonstrated compatibility of all of its components. The drug release study indicated that the pure drug had limited practicality for in vivo use. However, incorporating the drug into niosomes significantly improved its release profile, making it more suitable for practical use.

Hyaluronic acid-functionalized carboxymethyl dextran-coated melatonin nanoconjugates for targeted etoposide delivery in metastatic colon cancer: Extensive in-vitro investigation in HCT116 cell lines, antimicrobial efficacy, and anti-angiogenic potential in chick chorioallantoic membrane (CAM) assay

Managing advanced colon cancer is challenging, requiring targeted therapies. This study presents a novel nanoconjugate system, HA-CMD@ETP-MLT-NCs, designed to deliver etoposide (ETP) specifically to colon cancer cells. The system consists of Hyaluronic Acid (HA)-Functionalized Carboxymethyl Dextran (CMD) coated with Melatonin (MLT). The nanoconjugates showed good stability, with a zeta potential of −29.90 mV and a particle size of 199.1 nm. They achieved an 80.3 % yield and a high drug entrapment efficiency of 93.4 %. In vitro release studies demonstrated pH-dependent drug release, with 73.4 % released at pH 5.5 (tumour-like environment) and 42.6 % at pH 7.4 (normal tissue) over 24 h. The nanoconjugates improved cellular uptake, induced apoptosis, and reduced reactive oxygen species (ROS) in HCT116 colon cancer cells. Flow cytometry showed a significant decrease in ROS levels, and lipid peroxidation inhibition increased to 56.67 %. These findings suggest that HA-CMD@ETP-MLT-NCs enhance etoposide delivery and reduce side effects. Further in vivo studies and clinical trials are needed to confirm its therapeutic potential.

The Effect of Multilayer Nanoemulsion on the In Vitro Digestion and Antioxidant Activity of β-Carotene.

The objectives of this study were to design multilayer oil-in-water nanoemulsions using a layer-by-layer technique to enhance the stability of β-carotene and evaluate its effect on in vitro release and antioxidant activity. To prepare β-carotene-loaded multilayer nanoemulsions (NEs), a primary NE (PRI-NE) using Tween 20 was coated with chitosan (CS) for the secondary NE (SEC-CS), and with dextran sulfate (DS) and sodium alginate (SA) for the two types of tertiary NEs (TER-DS, TER-SA). The multilayer NEs ranged in particle size from 92 to 110 nm and exhibited high entrapment efficiency (92-99%). After incubation in a simulated gastrointestinal tract model, the release rate of free fatty acids decreased slightly after coating with CS, DS, and SA. The bioaccessibility of β-carotene was 7.02% for the PRI-NE, 7.96% for the SEC-CS, 10.88% for the TER-DS, and 10.25% for the TER-SA. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging abilities increased by 1.2 times for the multilayer NEs compared to the PRI-NE. In addition, the cellular antioxidant abilities improved by 1.8 times for the TER-DS (87.24%) compared to the PRI-NE (48.36%). Therefore, multilayer nanoemulsions are potentially valuable techniques to improve the stability, in vitro digestion, and antioxidant activity of β-carotene.

Preparation and characterization of niosomes for the delivery of a lipophilic model drug: comparative stability study with liposomes against phospholipase-A2

Vesicular nanocarriers like niosomes and liposomes are widely researched for controlled drug delivery systems, with niosomes emerging as promising alternatives due to their higher stability and ease of manufacturing. This study aimed to develop and characterize a niosomal formulation for the encapsulation and sustained release of temozolomide (TMZ), a model lipophilic drug, and to compare the stability of niosomes and liposomes, with a particular focus on the behavior of their lipid bilayers. Niosomes were prepared using the thin-film hydration method, composed of Span 60 (Sorbitan monostearate), cholesterol, and soy lecithin in varying molar ratios. The study investigated critical properties such as drug loading capacity, release kinetics, and resistance to enzymatic degradation. The optimized formulation was analyzed for drug entrapment efficiency and stability against phospholipase A2 (PLA2) degradation. The optimized niosomal formulation, with a 4:2:1 molar ratio of Span 60: cholesterol, achieved a high TMZ entrapment efficiency of 73.23 ± 1.02% and demonstrated sustained drug release over 24 hours. In comparison, liposomes released their TMZ payload within 4 hours upon exposure to PLA2, while the niosomes maintained their release profile, indicating superior stability. Spectroscopic and thermal analysis confirmed successful drug encapsulation with no component incompatibilities.

Optimization of the experimental design parameters for synthesis of Fluconazole loaded transethosomes as nano-based antifungal vesicles

Introduction: Antifungal drugs formulated in conventional pharmaceutical forms are not fully effective due to various factors. New approaches have focused on transdermal delivery drugs, including transethosomes, where the mixture of ethanol and surfactant allows a deeper drug skin’s penetration. Formulation parameters and process variables can make their optimization a considerable challenge. This study aimed to formulate Fluconazole-loaded transethosomes using a full-factorial design with the goal of optimizing formulation and process variables. Method: Fluconazole transethosomes were developed using the cold Method. A 21,31 full-factorial design was created by Design Expert® Software, where the impact of surfactant’s type and soy lecithin to surfactant ratio on resulting formulation were investigated. The formulations were tested for vesicle size, polydispersity index, zeta potential and entrapment efficiency. Results: Formulations containing Tween®80 presented the smaller particle sizes and showed a considerable entrapment efficiency for Fluconazole, they were more homogenous and highly stable compared to those prepared with Span®80. The optimized soy lecithin to surfactant ratio of 90:10 with Tween®80 was deemed apt for the synthesis of transethosomes giving the optimal formulation with a small particle size (300.2±5.57 nm), a low PDI (0.203±0.004), a good zeta potential (−31.75±0.68 mV) and a high entrapment efficiency (88.11±0.74 %). Conclusion: This study enabled the in-depth identification and optimization of the key factors involved in the experimental process, such as the type of surfactant used and the soybean lecithin-to-surfactant ratio. To ensure safety and effectiveness in use, this work provides the perspective of continuing the study by evaluating the antifungal activity, long-term stability and safety of Fluconazole-loaded transethosomes.

Bioavailability enhancement of atazanavir sulphate using mixed micelles: in vitro characterization and in vivo pharmacokinetic study.

This study aims to enhance the oral bioavailability of atazanavir sulphate, a human immunodeficiency virus-1 protease inhibitor known for its poor oral absorption, by formulating mixed micelles using Soluplus® and Kolliphor HS 15. Mixed micelles were prepared through the thin film hydration technique. The micelles were characterized for particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, drug loading, and confirmed for atazanavir sulphate encapsulation via FTIR studies. In vitro release studies were conducted, and the morphology of the micelles was examined using TEM. Atazanavir sulphate mixed micelles exhibited a particle size of 62.92nm, PDI of 0.221, zeta potential of - 17.8mV, high entrapment efficiency (99.76 ± 1.06), and drug loading (14 ± 0.82). In vitro release studies demonstrated sustained release up to 12h, with maximum solubility observed at 2h under pH 1.2 conditions. TEM analysis revealed spherical micelle morphology. Oral administration of atazanavir sulphate mixed micelles showed a 1.23-fold increase in relative bioavailability compared to pure drug suspension. The formulation of mixed micelles using Soluplus® and Kolliphor HS 15 offers a promising strategy to improve the oral bioavailability of atazanavir sulphate. These findings suggest the potential utility of mixed micelles as an effective delivery system for atazanavir sulphate, offering enhanced therapeutic outcomes for patients.

Box–Behnken design for the development of fluconazole-loaded classical ethosomes

Introduction: Ethosomes are soft and flexible vesicles mainly composed of phospholipids, ethanol and water. The presence of a high amount of ethanol ensure deeper drug penetration; however, an optimal formulation is necessary. This study aims to develop and characterize Fluconazole loaded classical ethosomes using Box-Behken design, in order to achieve to an optimal formulation having a minimal vesicle size, low polydispersity index, high zeta potential and good entrapment efficiency (% EE). Methods: Fluconazole ethosomes were prepared using cold method and tested for vesicle size, polydispersity index, zeta potential and EE%. Box-Behken design was created using Design Expert® Software, where the impact of sonication time and amount of ethanol and soybean lecithin on resulting formulation were investigated. Results: It was determined that increasing the concentration of ethanol up to an optimized limit reduces vesicle size and improves % EE. It was also observed that soybean lecithin concentrations affected positively vesicle size but negatively % EE. Whereas sonication time had an inverse effect both on, vesicle size and EE%. All prepared formulations showed a low polydispersity index and a good zeta potential indicating homogeneity and high stability. Therefore, the optimal formulation had % EE of 80.05±0.306 % and vesicular size of 226.501±5.34 nm with polydispersity index of 0.487±0.0078. Conclusion: In summary, using Box-Behnken design can enhance the understanding of the correlations between the variables involved in ethosome formation and their effects on vesicle size, polydispersity index and % EE. The optimal formulation obtained can be incorporated into drug delivery systems to enhance skin permeation and antifungal activity.

Nanostructured lipid carrier formulation for delivering poorly water-soluble ITF3756 HDAC inhibitor

Histone deacetylases (HDACs) are enzymes that play crucial roles in cellular processes by hydrolyzing acetyl-L-lysine side chains in core histones, thereby regulating gene expression and maintaining homeostasis. Histone deacetylase inhibitors (HDACi) have emerged as promising agents, particularly in cancer treatment, due to their ability to induce cytotoxic and pro-apoptotic effects. Selective HDAC6 inhibitors, such as ITF3756, have shown low off-target toxicity and promising pharmacological activities, but their poor water solubility limits their application in nanoparticulate drug delivery systems. Here, we optimized a nanostructured lipid carrier (NLC) formulation for delivering ITF3756 using the design of experiments (DOE) and response surface methodology (RSM). An interaction between the factor surfactant and formulation volume was observed, thus demonstrating that the surfactant concentration impacts the NLC size. It can be speculated that the higher the amount of the drug in the formulation, the lower the polydispersion index (PDI), thus resulting in more stable nanostructures. The optimized ITF3756-NLC demonstrated a size of 51.1 ± 0.3 nm, 8.85 ± 4.71 mV charge, and high entrapment efficiency (EE%), maintaining stability for 60 days. Moreover, ITF3756-NLC enhanced α-tubulin acetylation in melanoma, lung, and brain cancer cell lines, indicating retained or improved bioactivity. The ITF3756-NLC formulation offers a viable approach for enhancing the bioavailability and therapeutic efficacy of HDAC6 inhibitors, demonstrating potential for clinical applications in cancer immunotherapy.

Synthesis and characterization of chitosan-pectin fabricated nanoemulsion for ethylhexyl triazone topical delivery

This study aimed to investigate the stability of nanoemulsions for the UVB filter, ethylhexyl triazone (EHT) encapsulation followed by fabrication with chitosan and pectin. Four formulations were developed to assess the influence of hydrophile-lipophile balance (HLB) values on nanoemulsion stability for EHT encapsulation, targeting high Sun Protection Factor (SPF) values. The selected nanoemulsion was then subjected to fabrication with chitosan and pectin, followed by physical characterization and rheological behaviour study. Results indicated that all nanoemulsions exhibited particle sizes ranging from 137.7 nm to 206.0 nm and high entrapment efficiency from 88.76 % to 91.98 %. Sample N3, containing 1 % Tween 20 and 2 % polyethylene glycol (PEG) 400 with HLB of 12, demonstrated the highest stability, yielding a significantly elevated SPF value (10.33). Moreover, polymer-coated nanoemulsions with a low concentration of chitosan (0.1 %) showed enhanced stability when combined with different percentages of pectin. Polymer-coated nanoemulsions indicated shear-thinning behaviour at lower shear rates to Newtonian flow at higher shear rate. Furthermore, both polymer-coated and uncoated nanoemulsions exhibited decreased viscosity with increasing temperature. Also, polymer-coated nanoemulsions was found to enhance the sustainable release of EHT. These findings demonstrated the potential of polymer-coated nanoemulsions for skin application, offering enhanced stability and improved flow behaviour. The design of polymer-coated nanoemulsions could potentially minimize the risks of accumulation and toxicity of UV filters by providing a sustainable release behaviour.

Experimental Design for Optimization of Felbamate Nanosuspension Using Box-Behnken Design.

Felbamate, a valuable antiepileptic drug, suffers from low water solubility and potential side effects, limiting its therapeutic application. This study addresses this challenge by developing a felbamate nanosuspension for nose-to-brain delivery using a three-factor, three-level Box-Behnken design. The research focused on identifying the optimal combination of key formulation variables, chitosan concentration, chitosan/sodium tripolyphosphate ratio, and Tween 80 surfactant concentration to achieve a nanosuspension with desirable particle size, polydispersity index, and high entrapment efficiency (%EE), all critical parameters for efficient drug delivery via the nasal route. The study identified an optimized formulation consisting of 0.176% chitosan, a 3.3:1 chitosan/TPP ratio, and 1.55% Tween 80 through rigorous experimentation and response surface methodology analysis. The optimized formulation yielded a nanosuspension of 115.0 ± 4.37 nm mean particle size, 0.118 ± 0.021 polydispersity index, and +34.08 ± 2.4 mV zeta potential, indicating a stable system with a narrow size distribution suitable for enhanced drug delivery. The entrapment efficiency of 93.18 ± 1.69% confirmed effective encapsulation, while in-vitro dissolution studies demonstrated a significantly higher dissolution rate compared to pure felbamate, suggesting improved bioavailability. The results emphasize the capacity of this optimized nanosuspension to improve the therapeutic efficacy of felbamate and hence justify additional preclinical and clinical research.

Nano-vesicular systems for melanocytes targeting and melasma treatment: In-vitro characterization, ex-vivo skin retention, and preliminary clinical appraisal

Melasma represents an acquired melanogenesis disorder resulting in skin’s hyperpigmentation effect. Although several approaches are adopted for melasma treatment, nanotechnology presents the most convenient one. Therefore, the present work aimed to formulate and characterize three nano-vesicular systems namely, liposomes, penetration enhancer containing vesicles (PEVs) and invasomes to enhance the topical delivery of the skin whitening agent; alpha arbutin (α-arbutin) for the treatment of melasma. Liposomes were prepared according to a 23 full factorial design and the selected formula was further employed for the preparation of PEVs and invasomes. Results showed that the three vesicular systems exhibited nano-sizes ranging from 151.95 to 672.5 nm, negative charges ranging from −12.50 to −28.20 mV, high entrapment efficiencies ranging from 80.59 to 99.53 %, good stability and prolonged-release of α-arbutin for 24 h after dispersion in hydrogel form. The deposition study from the vesicular hydrogel confirmed their effectiveness for the drug’s accumulation in the skin reaching an average of 1.6-fold higher in the stratum corneum, 1.6–1.8-fold higher in the epidermis, and 1.6–1.8-fold higher in the dermis compared to the free drug dispersion in hydrogel. A preliminary clinical split-face study on patients suffering from melasma revealed that α-arbutin-loaded liposomes and PEVs in hydrogel forms showed better clinical outcomes compared to the free α-arbutin hydrogel as well as to the previously published α-arbutin encapsulated in chitosan nanoparticles and dispersed in hydrogel form. This delineates the aforementioned nano-vesicular systems as effective and clinically superior delivery means for melasma management.

Emerging Applications of Herbal-Based Nanocosmeceuticals for Beauty and Skin Therapy

: Herbal cosmeceuticals are a rapidly expanding sector of the personal care industry, and their use has greatly expanded over time. The advancement of research and development is demonstrated by nanotechnology, which boosts product efficacy by delivering innovative solutions. The application of nanotechnology is growing in the field of cosmeceuticals to address numerous shortcomings of conventional herbal products. Lower penetration and high compound instability of various cosmetic products for prolonged and enhanced compound delivery to beauty-based skin therapy are the main problems with the use of phyto-based cosmeceuticals. Nanosized delivery technologies are currently being used in cosmeceutical industries and products for prolonged and improved delivery of phyto-derived bioactive chemicals to solve these drawbacks. The aseptic sensation of many cosmeceutical products is improved by nanosizing phytocompounds, which also improve skin-protective properties and sustained delivery. Nanocosmeceuticals are now commonly utilized on skin, hair, lips, and nails to treat disorders including wrinkles, photoaging, hyperpigmentations, dandruff, hair damage, chapped lips, etc. Some of the cutting-edge nanotechnologies now being used for improved delivery of the phytoconstituents in skin care therapy include liposomes, ethosomes, glycerosomes, transferosomes, niosomes, phytosomes, nanostructured lipid carriers, solid lipid nanoparticles, polymeric nanoparticles, nanoemulsions, nanogels, etc. The advantages of these novel nanocarriers include improved skin penetration, controlled and prolonged drug release, increased stability, site-specific targeting, high entrapment efficiency, and improved bioavailability. Several phytoconstituents such as curcumin, aloe vera, resveratrol, lycopene, tocopherol, quercetin, catechins, and lutein have been successfully nanosized by employing various delivery technologies and incorporated in various gels, lotions, and creams for skin, lip, hair, and nail care for their sustained effects. The present article primarily focuses on the use of phytocompounds in various cosmeceutical products, diverse classes of innovative nanocarriers employed for delivering herbal nanocosmeceuticals, and the use of various phytobioactive compounds in novel nanocosmeceutical formulations to improve skin-based therapy.