Ethosomal systems are novel lipid vesicular carriers containing a relatively high percentage of ethanol. These nanocarriers are especially designed for the efficient delivery of therapeutic agents with different physicochemical properties into deep skin layers and across the skin. Ethosomes have undergone extensive research since they were invented in 1996; new compounds were added to their initial formula, which led to the production of new types of ethosomal systems. Different preparation techniques are used in the preparation of these novel carriers. For ease of application and stability, ethosomal dispersions are incorporated into gels, patches, and creams. Highly diverse in vivo models are used to evaluate their efficacy in dermal/ transdermal delivery, in addition to clinical trials. This article provides a detailed review of the ethosomal systems and categorizes them on the basis of their constituents to classical ethosomes, binary ethosomes, and transethosomes. The differences among these systems are discussed from several perspectives, including the formulation, size, ζ-potential (zeta potential), entrapment efficiency, skin-permeation properties, and stability. This paper gives a detailed review on the effects of ethosomal system constituents, preparation methods, and their significant roles in determining the final properties of these nanocarriers. Furthermore, the novel pharmaceutical dosage forms of ethosomal gels, patches, and creams are highlighted. The article also provides detailed information regarding the in vivo studies and clinical trials conducted for the evaluation of these vesicular systems.

Traditional medical practitioners in Hawaii and Polynesia have used Morinda citrifolia\ud L. (Noni) for centuries to cure or prevent varieties of illnesses. The popularity of M. citrifolia as\ud a dietary supplement, a food functional ingredient, or as a natural health enhancer is increasing\ud throughout the world. M. citrifolia contains phytochemicals that own antibacterial, antiviral, antifungal,\ud antitumor, anthelminthic, analgesic, hypotensive, anti-inflammatory and immune enhancing\ud effects. Moreover, the increasing vogue of M. citrifolia has attracted industries to employ it as a part\ud of various products and for wide applications such as a natural source of medicines and chemical\ud reagents as well as a green insecticidal. The wide spread of M. citrifolia in tropical climate of the\ud globe, from USA to Brazil reaching to Tahiti, Malaysia and Australia, contributed in enriching\ud its uses and potentials due to the variation in harvest locations. M. citrifolia parts including fruits,\ud seeds, barks, leaves, and flowers are utilized on their own for individual nutritional and therapeutical\ud values, however, the fruit is considered to contain the most valuable chemical compounds. This\ud review discusses in details the industrial uses and the pharmacological activities of M. citrifolia fruit,\ud seed, leaf and root, along with their isolated phytochemical compounds, through describing the\ud conducted in vitro and in vivo studies as well as clinical data

Introduction: Colchicine is used for the treatment of gout, pseudo-gout, familial Mediterranean fever, and many other illnesses. Its oral administration is associated with poor bioavailability and severe gastrointestinal side effects. The drug is also known to have a low therapeutic index. Thus to overcome these drawbacks, the transdermal delivery of colchicine was investigated using transethosomal gels as potential carriers. Methods: Colchicine-loaded transethosomes (TEs) were prepared by the cold method and statistically optimized using three sets of 2⁴ factorial design experiments. The optimized formulations were incorporated into Carbopol 940^® gel base. The prepared colchicine-loaded transethosomal gels were further characterized for vesicular size, dispersity, zeta potential, drug content, pH, viscosity, yield, rheological behavior, and ex vivo skin permeation through Sprague Dawley rats’ back skin. Results: The results showed that the colchicine-loaded TEs had aspherical irregular shape, nanometric size range, and high entrapment efficiency. All the formulated gels exhibited non-Newtonian plastic flow without thixotropy. Colchicine-loaded transethosomal gels were able to significantly enhance the skin permeation parameters of the drug in comparison to the non-ethosomal gel. Conclusion: These findings suggested that the transethosomal gels are promising carriers for the transdermal delivery of colchicine, providing an alternative route for drug administration.

Azithromycin (AZM) is a macrolide antibiotic used for the treatment of various bacterial infections. The drug is known to have low oral bioavailability (37%) which may be attributed to its relatively high molecular weight, low solubility, dissolution rate, and incomplete intestinal absorption. To overcome these drawbacks, liquid (L) and solid (S) self-emulsifying drug delivery systems (SEDDs) of AZM were developed and optimized. Eight different pseudo-ternary diagrams were constructed based on the drug solubility and the emulsification studies in various SEDDs excipients at different surfactant to co-surfactant (Smix) ratios. Droplet size (DS) < 150 nm, dispersity (Đ) ≤ 0.7, and transmittance (T)% > 85 in three diluents of distilled water (DW), 0.1 mM HCl, and simulated intestinal fluids (SIF) were considered as the selection criteria. The final formulations of L-SEDDs (L-F1_(H)), and S-SEDDs (S-F1_(H)) were able to meet the selection requirements. Both formulations were proven to be cytocompatible and able to open up the cellular epithelial tight junctions (TJ). The drug dissolution studies showed that after 5 min > 90% and 52.22% of the AZM was released from liquid and solid SEDDs formulations in DW, respectively, compared to 11.27% of the pure AZM, suggesting the developed SEDDs may enhance the oral delivery of the drug. The formulations were stable at refrigerator storage conditions.

Verapamil is a calcium channel blocker and highly effective in the treatment of hypertension, angina pectoris, and other diseases. However, the drug has a low bioavailability of 20 to 35% due to the first pass effect. The main objective of this study was to develop hybrid verapamil-dextran nanostructured lipid carriers (HVD-NLCs) in an attempt to increase verapamil cellular uptake. The formulations were successfully prepared by a high-shear homogenization method and statistically optimized using 24 full factorial design. The HVD-NLCs formulations were freeze-dried using trehalose as a cryoprotectant. The results showed that the optimized formula (VER-9) possessed a particle size (PS), polydispersity index (PDI), and the percentage of entrapment efficiency (%EE) of 192.29 ± 2.98, 0.553 ± 0.075, and 93.26 ± 2.66%, respectively. The incorporation of dextran sulfate in the formulation had prolonged the release of verapamil (~ 85% in 48 h) in the simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8). The differential scanning calorimetry analysis showed no chemical interaction between verapamil and the excipients in the formulation. While wide-angle X-ray scattering studies demonstrated the drug in the amorphous form after the incorporation in the NLCs. The transmission electron microscopy and scanning electron microscopy images revealed that the nanoparticles had spherical shape. The cellular uptake study using Caco-2 cell line showed a higher verapamil uptake from HVD-NLCs as compared to verapamil solution and verapamil-dextran complex. The optimized formulation (VER-9) stored in the refrigerated condition (5 °C ± 3 °C) was stable for 6 months. In conclusion, the HVD-NLCs were potential carriers for verapamil as they significantly enhanced the cellular uptake of the drug.