The main purpose of this study was to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) of Olmesartan (OLM) for enhancement of its solubility and dissolution rate. In this study, liquid SNEDDS containing Olmesartan was formulated and further developed into a solid form by the spray drying technique using Aerosil 200 as a solid carrier. Based on the preliminary screening of different unloaded SNEDDS formulae, eight formulae of OLM loaded SNEEDS were prepared using Capryol 90, Cremophor RH40 and Transcutol HP as oil, surfactant and cosurfactant, respectively. Results showed that the mean droplet size of all reconstituted SNEDDS was found to be in the nanometric range (14.91–22.97 nm) with optimum PDI values (0.036–0.241). All formulae also showed rapid emulsification time (15.46 ± 1.34–24.17 ± 1.47 s), good optical clarity (98.33% ± 0.16%–99.87% ± 0.31%) and high drug loading efficiency (96.41% ± 1.20%–99.65% ± 1.11%). TEM analysis revealed the formation of spherical and homogeneous droplets with a size smaller than 50 nm. In vitro release of OLM from SNEDDS formulae showed that more than 90% of OLM released in approximately 90 min. Optimized SNEDDS formulae were selected to be developed into S-SNEDDS using the spray drying technique. The prepared S-SNEDDS formulae were evaluated for flow properties, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), reconstitution properties, drug content and in vitro dissolution study. It was found that S-SNEDDS formulae showed good flow properties and high drug content. Reconstitution properties of S-SNEDDS showed spontaneous self-nanoemulsification and no sign of phase separation. DSC thermograms revealed that OLM was in solubilized form and FTIR supported these findings. SEM photographs showed smooth uniform surface of S-SNEDDS with less aggregation. Results of the in vitro drug release showed that there was great enhancement in the dissolution rate of OLM. To clarify the possible improvement in pharmacokinetic behavior of OLM S-SNEDDS, plasma concentration-time curve profiles of OLM after the oral administration of optimized S-SNEDDS formula (F3) were compared to marketed product and pure drug in suspension. At all time points, it was observed that OLM plasma concentrations in rats treated with S-SNEDDS were significantly higher than those treated with the drug in suspension and marketed product.

Miconazole nitrate (MIC) is an antifungal drug used for treatment of superficial fungal infections. However, it has low skin permeability. Hence, the objective of this study was to prepare miconazole nitrate using Transfersomes to overcome the barrier function of the skin. MIC Transfersomes were prepared using a thin lipid film hydration technique. The prepared Transfersomes were evaluated with respect to entrapment efficiency (EE%), particle size, and quantity of in vitro drug released to obtain an optimized formulation. The optimized formulation of MIC Transfersomes was incorporated into a Carbapol 934 gel base which was evaluated in comparison with a marketed product (Daktarin® cream 2%) for drug content, pH, spreadability, viscosity, in vitro permeation, and in vitro and in vivo antifungal activity. The prepared MIC Transfersomes had a high EE% ranging from (67.98 ± 0.66%) to (91.47 ± 1.85%), with small particle sizes ranging from (63.5 ± 0.604 nm) to (84.5 ± 0.684 nm). The in vitro release study suggested that there was an inverse relationship between EE% and in vitro release. The kinetic analysis of all release profiles was found to follow Higuchi’s diffusion model. All independent variables had a significant effect on the dependent variables (p-values < 0.05). The prepared MIC transfersomal gel showed higher antifungal activity than Daktarin® cream 2%. Therefore, miconazole nitrate in the form of Transfersomes has the ability to penetrate the skin, overcoming the stratum corneum barrier.

Objectives: The study aimed to prepare carbamazepine in solid lipid nanoparticle form (CBZ-SLN) in order to enhance its anticonvulsant effect. Method: Eight formulations of CBZ-SLNs were prepared by homogenization and ultra-sonication techniques. Results: The prepared CBZ-SLN showed a high entrapment efficiency% (39.66 ± 2.42%–71.91 ± 1.21%), a small particle size (45.11 ± 6.72–760.7 ± 5.25 nm), and a negative zeta potential (from −21.5 ± 1.02 to −38.4 ± 1.32 mv). The in vitro release study showed the slow release of CBZ from SLNs compared to CBZ aqueous dispersion (p < 0.05). The infrared spectroscopy and the thermal analysis revealed the compatibility of the drug with other ingredients and the presence of drug in the more soluble amorphous estate, respectively. The in vivo study on mice revealed that the CBZ-SLN had a higher anticonvulsant efficacy than CBZ aqueous dispersion after a lethal and chronic dose of pentylenetetrazole (PTZ) (p < 0.05). The histopathological examination of the hippocampus revealed a decrease in the percentage of degeneration in mice treated with the CBZ-SLN compared to the PTZ and CBZ groups. Conclusion: CBZ can be formulated as SLN with higher anticonvulsant activity than free CBZ aqueous dispersion.

The objective of this study was to formulate and evaluate valsartan (VLT) ethosomes to prepare an optimized formula of VLT-entrapped ethosomes that could be incorporated into a sustained release transdermal gel dosage form. The formulation of the prepared ethosomal gel was investigated and subjected to in vitro drug release studies, ex vivo test, and in vivo studies to assess the effectiveness of ethosomal formulation in enhancing the bioavailability of VLT as a poorly soluble drug and in controlling its release from the transdermal gel dosage form. The acquired results are as follows: Dependent responses were particle size, polydispersity index, zeta potential, and entrapment efficiency. The optimized VLT-ETHs had a nanometric diameter (45.8 ± 0.5 nm), a negative surface charge (−51.4 ± 6.3 mV), and a high drug encapsulation (94.24 ± 0.2). The prepared VLT ethosomal gel (VLT-ethogel) showed a high peak plasma concentration and enhanced bioavailability in rats compared with the oral solution of valsartan presented in the higher AUC (0–∞). The AUC (0–∞) with oral treatment was 7.0 ± 2.94 (μg.h/mL), but the AUC (0–∞) with topical application of the VAL nanoethosomal gel was 137.2 ± 49.88 (μg.h/mL), providing the sustained release pattern of VLT from the tested ethosomal gel.

(1) Background: Thymus vulgaris L. (thyme) essential oil (TEO) has gained much attention because of its long history of medicinal usage. However, the lack of precise chemical profiling of the TEO and methods to optimize the bioactivity and delivery of its constituents has hampered its research on quality control and biological function; (2) Methods: The current study aimed to analyze the TEO’s chemical composition using the GC-MS method and identify its key components. Another objective of this work is to study the impact of the protective layer of amphiphilic oligochitosan (AOC) on the physicochemical stability and transdermal potentials of TEO multilayer nanoemulsions formulated by the incorporation of TEO, Tween80, lecithin (Lec), and AOC; (3) Results: The AOC protective layer significantly improved the stability of TEO-based NEs as revealed by the constancy of their physicochemical properties (particle size and zeta potential) during storage for a week. Excessive fine-tuning of thyme extract NEs and the AOC protective layer’s persistent positive charge have been contributed to the thyme extract’s improved anti-inflammatory, transdermal, and anti-melanoma potentials; (4) Conclusions: the AOC-coated NEs could offer novel multifunctional nanoplatforms for effective transdermal delivery of lipophilic bioactive materials.

Cancer is a multifactorial disease necessitating identification of novel targets for its treatment. Inhibition of Bcl-2 for triggered pro-apoptotic signaling is considered a promising strategy for cancer treatment. Within the current work, we aimed to design and synthesize a new series of benzimidazole- and indole-based derivatives as inhibitors of Bcl-2 protein. The market pan-Bcl-2 inhibitor, obatoclax, was the lead framework compound for adopted structural modifications. The obatoclax’s pyrrolylmethine linker was replaced with straight alkylamine or carboxyhydrazine methylene linkers providing the new compounds. This strategy permitted improved structural flexibility of synthesized compounds adopting favored maneuvers for better fitting at the Bcl-2 major hydrophobic pocket. Anti-cancer activity of the synthesized compounds was further investigated through MTT-cytotoxic assay, cell cycle analysis, RT-PCR, ELISA and DNA fragmentation. Cytotoxic results showed compounds 8a, 8b and 8c with promising cytotoxicity against MDA-MB-231/breast cancer cells (IC₅₀ = 12.69 ± 0.84 to 12.83 ± 3.50 µM), while 8a and 8c depicted noticeable activities against A549/lung adenocarcinoma cells (IC₅₀ = 23.05 ± 1.45 and 11.63 ± 2.57 µM, respectively). The signaling Bcl-2 inhibition pathway was confirmed by molecular docking where significant docking energies and interactions with key Bcl-2 pocket residues were depicted. Moreover, the top active compound, 8b, showed significant upregulated expression levels of pro-apoptotic/anti-apoptotic of genes; Bax, Bcl-2, caspase-3, -8, and -9 through RT-PCR assay. Improving the compound’s pharmaceutical profile was undertaken by introducing 8b within drug-solid/lipid nanoparticle formulation prepared by hot melting homogenization technique and evaluated for encapsulation efficiency, particle size, and zeta potential. Significant improvement was seen at the compound’s cytotoxic activity. In conclusion, 8b is introduced as a promising anti-cancer lead candidate that worth future fine-tuned lead optimization and development studies while exploring its potentiality through in-vivo preclinical investigation.