Formulation, Characterization, and Optimization of a Topical Gel Containing Tranexamic Acid to Prevent Superficial Bleeding: In Vivo and In Vitro Evaluations.

Objectives: Tranexamic acid (TXA) is used systemically to stop bleeding, but it can lead to thromboembolism. Trials have revealed the efficacy of topical TXA on local hemorrhages. However, there is a need for an efficient delivery system that can keep the drug at the site of action. Materials and Methods: To develop a gel containing TXA (3%) optimized in terms of viscosity and dispersibility, the central composite design based on two factors-three levels [carbopol 940 and hydroxypropyl methylcellulose (HPMC), 1-1.5% and 1-2%, respectively] was applied. The spreadability and viscosity were assessed using glass slide and rheometer, respectively. To confirm the compatibility of TXA with the gel, fourier transform-infrared (FTIR) spectroscopy was performed. Drug content uniformity was analyzed by a spectroscopy method. An ex vivo mice model using Franz cells was applied to evaluate the permeation of TXA through the skin. To investigate the effect of topical TXA gel on bleeding time, IVY human method was performed. Results: HPMC/carbopol 940 (1:1, w/w) gel showed the highest quality in terms of viscosity and dispersibility (3.982 ± 17.6 and 6.052 ± 3.562, respectively). FTIR absorption spectrum showed that all the TXA index peaks appeared without displacement. The complete-encapsulated TXA content was uniformly dispersed throughout the gel. In vitro TXA cumulative release reached 90% in 4 h. The bleeding time determined in vivo for TXA gel was significantly lower than that for TXA solution and control. Conclusion: The results confirm the importance of further studies on this formulation as a potential medication to stop acute superficial bleeding.

Solid lipid nanoparticles (SLNs), the potential novel vehicle for enhanced in vivo efficacy of hesperidin as an anti-inflammatory agent.

Hesperidin (C28H34O15), a flavanone glycoside abundantly present in citrus fruits, has proven therapeutic effects including anti-inflammatory activities. Herein, we report a novel formulation of HESP loaded solid lipid nanoparticles (SLNs) using hot homogenization and ultrasound to improve the poor solubility and bioavailability. In the present study, the formulation was developed and optimized by response surface method and then characterized by scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy (FT-IR), and dynamic light scattering (DLS). Encapsulation efficiency was determined and the anti-inflammatory effect was assessed through in vivo ear edema inflammation model. According to the electron microscopy results, the product has a spherical shape. The optimized parameters produced small size (179.8 ± 3.6 nm) HESP-SLNs with high encapsulation efficiency (93.0 ± 3.8 %). The outcomes exhibited that encapsulation in SLNs carriers improves the anti-inflammatory potential of HESP.

Melanoma-derived exosomes: Versatile extracellular vesicles for diagnosis, metastasis, immune modulation, and treatment of melanoma.

Malignant melanoma is one of the most aggressive human neoplasms responsible for the majority of skin cancer-related deaths in its advanced stages. Achieving a thorough knowledge of reliable tumor-originated biomarkers and molecular mechanisms can provide many practical approaches and guide the way towards the design of rational curative therapies to improve the survival rate of patients. Cancer cells, including melanoma cells, release high amounts of a broad family of nanovesicles, containing different biochemical messages. Exosomes are a type of extracellular vesicles (EVs) that are generated by different cell populations and participate in the intercellular communication of surrounding and distant cells/tissues. Exosome cargo consists of several biologically active proteins and genomic components. Tumor cells tend to release exosomes throughout the tumor microenvironment, which affects the biological performance of recipient cells. Recent evidence provides new perspective in melanoma management, showing that melanoma-derived exosomes (MEXs) may represent a valuable tool for melanoma diagnosis and treatment. This review presents a summary of the potential role of MEXs in the early diagnosis of melanoma. More importantly, we also discuss the capacity of MEXs in reproducing numerous tumor-related functions required for angiogenesis, immune system modulation, induction of migration and metastatic spread, tumor chemotherapy resistance, and melanoma tumor progression and survival. Considering the advent of novel bioengineering and immunotherapy approaches, natural exosomes can be exerted as nanocarriers and cancer vaccines to facilitate the conduction of more efficient cancer treatment.

Preparation and Characterization of Nanostructured Lipid Carrier (NLC) and Nanoemulsion Containing Vitamin D3.

Vitamin D is an essential vitamin for bone marrow development and immune function, which is mostly synthesized in the skin through sun exposure. The high global prevalence of vitamin D deficiency requires a feasible approach to administer vitamin D to a larger number of population in a shorter amount of time, and this may be achieved through food fortification. Food fortification using nanostructured lipid carriers (NLC) and nanoemulsions appears to be an ideal method to enhance bioavailability, stability, and solubility of bioactive compounds. The aim of this study was to develop NLC and nanoemulsion forms of vitamin D to evaluate its efficacy for further enrichment of dairy products. NLC containing Precirol and nanoemulsion containing vegetable oils were prepared and characterized for polydispersity index, particle size, zeta potential, particle shape, crystal properties, stability, encapsulation efficiency, and releasing. Vitamin D3 NLC size was in the range of 123.4 to 210.6 nm and for nanoemulsion 137.6 to 171.6 nm, respectively. Optimal NLC and nanoemulsion carriers were selected for morphological assessment, encapsulation efficiency, thermal analysis, and release study. Scanning and transmission electron microscopy revealed that particles had approximately spherical shape. In gastric simulated solution (pH = 1.2), NLC and nanoemulsion form of vitamin D3 released 9.3% and 26.9% of vitaminD3, respectively. This indicated that our formulation is able to protect vitamin D3 under acidic conditions. The results of this study revealed that NLC and nanoemulsion could be an optimal carrier for food fortification in order to improve bioavailability of bioactive compounds such as vitamin D.

Preparation, characterization, and optimization of auraptene-loaded solid lipid nanoparticles as a natural anti-inflammatory agent: In vivo and in vitro evaluations.

Auraptene (AUR) is a bioactive antioxidant coumarin with valuable pharmacological properties; however, poor water solubility is a substantial issue for the topical application of AUR. Therefore, we sought to prepare solid lipid nanoparticles (SLNs) containing AUR (AUR-SLNs) to enhance its anti-inflammatory effect. The prepared formulations were optimized by applying the response surface method. Furthermore, AUR-SLNs were compared to conventional cream containing AUR regarding both the permeation rate of the nanoparticles and the anti-inflammatory effect through both in vitro and in vivo studies. Particle size and entrapment efficiency of the optimized formulation were 140.9 ±â€¯3.55 nm and 84.11% ±â€¯3.30, respectively. Transmission electron microscopy revealed that the nanoparticles were spherical. Differential scanning calorimetry (DSC) analysis demonstrated no drug-lipid incompatibility in the formulation. Fourier transform-infrared spectroscopy (FTIR) spectra revealed the amorphous state of AUR and the encapsulation of this agent in SLNs. The in vitro permeation studies exhibited that AUR-SLNs could significantly enhance cutaneous uptake of AUR and skin targeting. The anti-inflammatory and histopathological studies exhibited no significant differences between AUR-SLNs and indomethacin. AUR-SLNs did not induce skin sensitization in guinea pigs. The results suggest that SLNs could be appropriate carriers for the topical application of AUR as a natural anti-inflammatory agent.

Encapsulation challenges, the substantial issue in solid lipid nanoparticles characterization.

Solid lipid nanoparticles (SLNs), as alternative colloidal carriers, have been used for the sustained release of lipophilic drugs with poor water solubility. One of the most important parameters in the characterization of SLNs is entrapment efficiency (EE). Despite the importance of this factor in estimating the drug loading capacity, EE does not always represent the exact percentage of the entrapped drug. Several variables such as the stirring speed and duration, and concentration of surfactant, emulsifier, and drug play important roles in determining the final EE. In addition, EE is mainly affected by the type and concentration of the lipid. There are two major methods for the measurement of EE are in which the encapsulated drug in SLNs is either directly measured (direct method) or the amount of unencapsulated drug in the supernatant is measured (indirect method). Accuracy of drug analysis is the main challenge for EE calculation, and is either performed in the separated aqueous medium or the particles. In this review, we aimed to introduce the available methods for EE determination in SLNs and discuss the advantages and shortcomings of each method.