Preparation, Characterization, and Evaluation of the Anticancer Effect of Mesoporous Silica Nanoparticles Containing Rutin and Curcumin.

AIMS AND OBJECTIVE: The aim of this study was the preparation of mesoporous silica nanoparticles co-loaded with rutin and curcumin (Rut-Cur-MSNs) and the assessment of its physicochemical properties as well as its cytotoxicity on the head and neck cancer cells (HN5). Besides, ROS generation of HN5 cells exposed to Rut-Cur-MSNs was evaluated. Several investigations showed that rutin and curcumin have potential effects as anticancer phytochemicals; however, their low aqueous solubility and poor bioavailability limited their applications. The assessment of physicochemical properties and anticancer effect of prepared nanoparticles was the objective of this study. METHODS: The physicochemical properties of produced nanoparticles were evaluated. The toxicity of Rut-Cur-MSNs on HN5 cells was assessed. In addition, the ROS production in cells treated with Rut-Cur-MSNs was assessed compared to control untreated cells. RESULTS: The results showed that Rut-Cur-MSNs have mesoporous structure, nanometer size and negative surface charge. The X-ray diffraction pattern showed that the prepared nanoparticles belong to the family of silicates named MCM-41. The cytotoxicity of Rut-Cur-MSNs at 24 h was significantly higher than that of rutin-loaded MSNs (Rut-MSNs) and curcumin-loaded MSNs (Cur-MSNs) (p<0.05). CONCLUSION: The achieved results recommend that the prepared mesoporous silica nanoparticles containing rutin and curcumin can be a useful nanoformulation for the treatment of cancer. The produced nanomaterial in this study can be helpful for cancer therapy.

Nano-invasomes for simultaneous topical delivery of buprenorphine and bupivacaine for dermal analgesia.

Opioid and local anaesthetic receptors are abundantly concentrated in different layers of the skin. Therefore, simultaneous targeting of these receptors can produce more potent dermal anaesthesia. Herein, we developed lipid-based nanovesicles for the co-delivery of buprenorphine and bupivacaine to efficiently target skin-concentrated pain receptors. Invasomes incorporating two drugs were prepared by ethanol injection method. Subsequently, the size, zeta potential, encapsulation efficiency, morphology, and in-vitro drug release of vesicles were characterized. Ex-vivo penetration features of vesicles were then investigated by the franz diffusion cell on the full-thickness human skin. Wherein, it was demonstrated that invasomes penetrated the skin deeper and delivered bupivacaine more effectively than buprenorphine to the target site. The superiority of invasome penetration was further evidenced by the results of ex-vivo fluorescent dye tracking. Estimation of in-vivo pain responses by the tail-flick test revealed that compared with the liposomal group, the group receiving invasomal formulation and drug-free invasomal formulation (only containing menthol) displayed increased analgesia in the initial times of 5 and 10 min. Also, no signs of oedema or erythema were observed in the Daze test in any of the rats receiving the invasome formulation. Finally, ex-vivo and in-vivo assays demonstrated efficiency in delivering both drugs into deeper layers of skin and exposing them to the located pain receptors, which improves the time of onset and the analgesic effects. Hence, this formulation appears to be a promising candidate for tremendous development in the clinical setting.

Preparation of rutin-loaded mesoporous silica nanoparticles and evaluation of its physicochemical, anticancer, and antibacterial properties.

BACKGROUND: The studies have shown that rutin has great potential as an anticancer and antimicrobial plant base agent; nevertheless, poor bioavailability and low aqueous solubility of rutin limit its application. One of the beneficial routes to increase the solubility and bioavailability of rutin is the development of nanoparticulate material. This study aimed to assess the anticancer and antibacterial effects of rutin-loaded mesoporous silica nanoparticles (RUT-MSNs). METHODS: RUT-MSNs were prepared and physicochemically characterized. The cytotoxicity of RUT-MSNs on the HN5 cells as head and neck cancer cells was evaluated. The expression level of apoptosis-related genes such as Bcl-2 and Bax genes were evaluated. In addition, ROS production of RUT-MSNs treated cells was assessed. In addition, minimum inhibitory concentration (MIC), biofilm, and attachment inhibitory effects of RUT-MSNs compared with free rutin were assessed against different bacterial strains. RESULTS: Transmission electron microscopy (TEM) showed mesoporous rod-shaped nanoparticles with an average particle size of less than 100 nm. RUT-MSNs displayed the cytotoxic effect with IC50 of 20.23 µM in 48 h of incubation time (p < 0.05). The elevation in the ratio of Bax/Bcl-2 was displayed within the IC50 concentration of RUT-MSNs in 48 h (p < 0.05). The antibacterial action of rutin was improved by loading rutin in MSNs to the nano-sized range in the MIC test. CONCLUSION: The anticancer and antibacterial effects of RUT-MSNs were considerably more than rutin. RUT-MSNs inhibited the growth of HN5 cells by inducing apoptosis and producing ROS. These results suggest that RUT-MSNs may be useful in the treatment of cancers and infections.

Evaluation of HER2/neu expression in different types of salivary gland tumors: a systematic review and meta-analysis.

This study is a systematic review and meta-analysis to assess the overexpression rate of HER2 in patients with salivary gland tumors. We included peer-reviewed publications from 1995 to 2020, indexed in medical databases, using search terms such as "human epidermal growth factor receptor 2 (HER2)" and "salivary gland tumors", and extracted relevant data. The extracted data were analyzed with RevMan 5.3 software. Intra-and intergroup post hoc analyses of outcome variables were performed using t-tests, and the rates of HER2 positivity among studies were evaluated. 80 studies were included in the analysis. The positive rates of HER2 ranged from 3.3% to 84.0% and 1% to 9% in malignant and benign subtypes, respectively. The highest HER2 overexpression rate among malignant tumors was in salivary ductal carcinomas (SDC), with a 45% positive rate (CI 95%: 21.9-70.3%). Mucoepidermoid carcinoma (MEC) had the highest positive rate of 84% (CI 95%: 74.1-90.0%). Among benign salivary gland tumors, the highest rate was found in myoepithelioma, with a positive rate of 9% (CI 95%: 1.7-33.6%). The highest rate of HER2 overexpression is present in malignant subtypes of salivary gland tumors, more specifically in salivary ductal carcinoma, mucoepidermoid carcinomas, salivary duct carcinoma in situ, and carcinoma ex pleomorphic adenoma.

Nanophytosomes for enhancement of rutin efficacy in oral administration for diabetes treatment in streptozotocin-induced diabetic rats.

Rutin is a natural antioxidant compound with several therapeutic benefits. However, the application of this bioactive compound is limited due to its low stability and bioavailability. To overcome these limitations, this study aimed to encapsulate rutin into nanophytosomes (NPs) and evaluate the therapeutic potency of this nanocarrier in streptozotocin (STZ)-induced diabetic rats. The particle size, zeta potential, and encapsulation efficiency of the prepared NPs were 72.72 nm, -22 mV, and 93.7%, respectively. The in vivo study showed that the oral administration of rutin-loaded NPs (containing 25 mg rutin/kg per day) for 4 weeks was more effective than free rutin in the control of hyperglycemia and hyperlipidemia in the STZ-induced diabetic rats. Additionally, the administration of rutin-loaded NPs regulated the activities of liver marker enzymes and the levels of total hemoglobin and glycated hemoglobin in the diabetic rats. The antioxidant defenses in the diabetic rats were increased by the administration of rutin-loaded NPs more than free rutin. Moreover, the histopathological study showed that the administration of rutin-loaded NPs restored the diabetes-induced damages in kidney, liver, and pancreas. In conclusion, encapsulation of rutin with phytosomes is an effective technique to benefit from its therapeutic potential, especially to attenuate diabetic complications.

Design and Evaluation of DentAll Mobile Software for Dental Education.

INTRODUCTION: The use of new learning methods to improve the educational processes is inevitable in the field of dentistry. Due to the positive effects of mobile learning on the students' learning and skills, we decided to design a software in the required areas. Considerations of systemic diseases, medications, emergencies, prophylaxis, tests interpretation, lesions diagnosis, cephalometric, and cast analysis were the topics required. METHODS: This semi-experimental study was carried out in Faculty of Dentistry, Tabriz University of Medical Sciences during 2020. DentAll software was developed using Android Studio software. It is an educational and decision-making support system. The satisfaction and perceptions of 10 professors, 5 post-graduate students, and 30 senior dental students about the designed software were assessed using a questionnaire based on a 5-part Likert scale. The senior students were invited and the pre-test was taken to assess the students' knowledge; then, the designed software was provided by the administrator. At the end of the process, the post-test was taken. Paired samples t-test was used to compare the results of the pre-test and post-test. The data were analyzed using the Statistical Package for Social Sciences (SPSS) 17.0. The significance level was established at a P < 0.05. RESULTS: The mean scores of the pre-test and post-test were 16.5 ± 1.49 and 18.2 ± 0.99, respectively. The statistical analysis showed that the difference between the mean scores of the pre-test and post-test was statistically significant (p< 0.001). 46.7% of the professors and post-graduate students expressed their overall satisfaction as very high, 46.7% as high, and 6.7% as average. Furthermore, 50% of the students expressed their overall satisfaction as very high, 36.7% as high, and 13.3% as moderate. CONCLUSION: The designed comprehensive software satisfied the students and the professors who used it and the students' scores increased after use. This software had capabilities such as easy access to the resources, learning anytime and anywhere, increasing the students' interest and motivation, etc. from the point of view of the commentators. To the best of our knowledge, this comprehensive educational aid has not been designed previously and it was effective in improving the students' learning, scientific knowledge and treatment planning.

Ki-67 expression as a diagnostic biomarker in odontogenic cysts and tumors: A systematic review and meta-analysis.

Ki-67 is a marker of cell proliferation, used as an important diagnostic marker in the pathologic differentiation of various lesions. It is also relevant for developing targeted molecular therapies. We carried out a systematic review to assess the Ki-67 labeling index (LI) in odontogenic cysts and tumors. Databases were searched, including PubMed (MEDLINE), Scopus, CINHAL, PsycoInfo, the Cochrane Library, and Proquest. The meta-analysis was carried out based on the data of 608 lesions. When a 5% cut-off point was set, ki-67 LI of all benign odontogenic tumors dropped below this point. All the malignant tumors demonstrated an LI of over 15.3%; a significantly higher Ki-67 LI in malignant odontogenic lesions (17.59±2.80) was observed. Among benign tumors, the largest and the smallest Ki-67 LIs were seen in ameloblastoma (4.39±0.47) and adenomatoid odontogenic tumor (0.91±1.71). The mean values of Ki-67 LI in tumors and cysts were 4.23 (0.38) and 1.04 (0.07), respectively. Among odontogenic cysts, the highest Ki-67 LI was found in odontogenic keratocyst (OKC) (3.58±0.51), and the lowest in the radicular cyst (1.29±0.62%). Ki-67 LIs in all odontogenic cysts were <3%, except for OKC. This controversial lesion seems to have a profile more similar to a tumor, and a treatment plan similar to tumors might be suggested. We found that odontogenic lesions have diverse proliferative activities that help differentiate between various lesions and suggest therapeutic plans.

Molecular mechanisms of anticancer effect of rutin.

Because of the extensive biological functions of natural substances such as bioflavonoids, and their high safety and low costs, they could have high priority application in the health care system. The antioxidant properties of rutin, a polyphenolic bioflavonoid, have been well documented and demonstrated a wide range of pharmacological applications in cancer research. Since chemotherapeutic drugs have a wide range of side effects and rutin is a safe anticancer agent with minor side effects so recent investigations are performed for study of mechanisms of its anticancer effect. Both in-vivo and in-vitro examinations on anticancer mechanisms of this natural agent have been widely carried out. Regulation of different cellular signaling pathways such as Wnt/ß-catenin, p53-independent pathway, PI3K/Akt, JAK/STAT, MAPK, p53, apoptosis as well as NF-ĸB signaling pathways helps to mediate the anticancer impacts of this agent. This study tried to review the molecular mechanisms of rutin anticancer effect on various types of cancer. Deep exploration of these anticancer mechanisms can facilitate the development of this beneficial compound for its application in the treatment of different cancers.

Role of vitamin D and vitamin D receptor (VDR) in oral cancer.

Oral cancer is known as one of the most common cancers, with a poor prognosis, related to delayed clinical diagnosis, either due to the lack of particular biomarkers related to the disease or costly therapeutic alternatives. Vitamin D executes its functions by interacting with the vitamin D receptor (VDR), both in healthy and diseased individuals, including oral cancer. This review discusses the role of vitamin D and VDR on tumorigenesis, emphasizing on oral cancer. Furthermore, regulation of VDR expression, mechanisms of anticancer effects of calcitriol, oral cancer chemoresistance and its relation with VDR and polymorphisms of VDR gene will be discussed. The manuscript is prepared mainly using the information collected from PubMed and MEDLINE.

A Comparative Study of Macrophage Density in Odontogenic Cysts and Tumors with Diverse Clinical Behavior.

STATEMENT OF THE PROBLEM: Macrophages are the target of attention in numerous diseases. Many studies reported them as the regulators of the growth, dissemination, and clinical behavior of various lesions. There are relatively scarce data regarding the role of macrophages in oral lesions, particularly odontogenic lesions. PURPOSE: This study investigated the macrophage density in odontogenic lesions of diverse biologic performance. MATERIALS AND METHOD: In this comparative analytical study, 60 cases of odontogenic lesions including ameloblastoma, keratocystic odontogenic tumor, dentigerous cyst, and radicular cyst were immunohistochemically stained with anti-CD68 antibody. One-way ANOVA and Tukey's HSD test were used for statistical analysis. RESULTS: The results showed that the macrophage density in keratocystic odontogenic tumor (35.72±7.74) and ameloblastoma (46.12±9.84) was not significantly different from that in dentigerous cyst (43.87±8.13). Interestingly, the macrophage density in keratocystic odontogenic tumor was lower than that in dentigerous cyst. No significant difference was observed in macrophage density between the ameloblastoma and much less aggressive lesions like dentigerous cyst (p= 0.59). Macrophage density in radicular cyst (81.53±11.04) was significantly higher than other odontogenic lesions (p< 0.001). CONCLUSION: The lack of significant differences in macrophage density between the known aggressive odontogenic tumors and much less aggressive lesions implied that macrophages might not contribute to the biological behavior of the odontogenic lesions. Therefore, it could support the notion that targeted therapy would not have prominent clinical potential to decrease the extent of mutilating surgeries in odontogenic lesions.

The role of macrophages and eosinophils in reactive lesions of the oral cavity.

BACKGROUND: Many studies have reported that macrophages and eosinophils are involved in the pathogenesis of several diseases. To the best of our knowledge, this is the first study comparing macrophages and eosinophils in oral reactive lesions. AIMS: In this study, we aimed to determine the contribution of macrophages and eosinophils to the pathogenesis of oral reactive lesions and the relationships between these biomarkers and the diverse histopathologic features. METHODS: Seventy-five paraffin-embedded tissue samples were assessed in this study. Five categories (15 cases for each group), including peripheral ossifying fibroma, pyogenic granuloma, fibroma, inflammatory fibrous hyperplasia, and peripheral giant-cell granuloma, were considered. Anti-CD68 immunohistochemical and hematoxylin-eosin staining was carried out. RESULTS: We found that macrophages, but not eosinophils, were a significant internal component of oral reactive lesions. Macrophages were observed in high densities in all studied groups and diffusely distributed or clustered throughout these lesions. The number of macrophages was increased in peripheral giant-cell granuloma compared with other groups. CONCLUSIONS: Our findings suggest that macrophages are involved in the pathogenesis and the variation of microscopic features of oral reactive lesions. However, further clinical studies should be conducted to identify the biological process behind macrophages and the molecular interactions of these cells, with the ultimate aim of suggesting a new potential therapeutic target for these lesions. We found that eosinophils were not involved in the fibrotic process and the variation of microscopic features in oral reactive lesions. Our results showed that peripheral giant-cell granulomas highly demonstrated histiocytic characteristics.

Comparing Serum and Salivary Levels of Vitamin D in Patients with Recurrent Aphthous Stomatitis and Healthy Individuals.

STATEMENT OF THE PROBLEM: Recurrent aphthous stomatitis (RAS) is the most prevalent ulcerative condition of the oral mucosa. Many studies have emphasized on immunologic factors as the reason of inducing RAS; however, the exact etiologic cause of RAS has not been identified yet. Vitamin D has an endocrine function and regulatory effects on the immune system. It has potential therapeutic effects on autoimmune diseases, psoriasis, and neoplasms. Vitamin D deficiency has been detected in some autoimmune diseases such as rheumatoid arteritis. PURPOSE: The aim of the present study was to compare the serum and salivary levels of vitamin D in patients with RAS and healthy individuals. MATERIALS AND METHOD: In this cross sectional study, patients with RAS, referring to the Department of Oral Medicine, Tabriz Faculty of Dentistry, were evaluated after taking medical history, clinical examinations, and completing an informed consent form. The serum and salivary vitamin D levels were compared between case (n=26) and control (n=26) groups. RESULTS: The mean serum vitamin D levels in the case and control groups were 33.0.7±12.41 and 50.89±9.30 (ng/dL), respectively, with a statistically significant difference (p<0.001). On the other hand, the mean salivary vitamin D levels in the case and control groups were 17.36± 8.01 and 20.79±6.31 (ng/dL), respectively, with no statistically significant difference (p= 0.09). In addition, the correlation between the serum and salivary levels of vitamin D was 56%, being statistically significant (p< 0.001). CONCLUSION: The serum levels of vitamin D in patients with RAS were significantly less than that in healthy individuals; however, there were no significant differences in salivary vitamin D levels between patients with RAS and healthy individuals. In addition, there was a significant and positive correlation between serum and salivary levels of vitamin D in all patients.

Nanoethosomal formulation of gammaoryzanol for skin-aging protection and wrinkle improvement: a histopathological study.

BACKGROUND: Free radical scavengers and antioxidants, with the main focus on enhanced targeting to the skin layers, can provide protection against skin ageing. OBJECTIVE: The aim of the present study was to prepare nanoethosomal formulation of gammaoryzanol (GO), a water insoluble antioxidant, for its dermal delivery to prevent skin aging. METHODS: Nanoethosomal formulation was prepared by a modified ethanol injection method and characterized by using laser light scattering, scanning electronic microscope (SEM) and X-ray diffraction (XRD) techniques. The effects of formulation parameters on nanoparticle size, encapsulation efficiency percent (EE%) and loading capacity percent (LC%) were investigated. Antioxidant activity of GO-loaded formulation was investigated in vitro using normal African green monkey kidney fibroblast cells (Vero). The effect of control and GO-loaded nanoethosomal formulation on superoxide dismutase (SOD) and malondialdehyde (MDA) content of rat skin was also probed. Furthermore, the effect of GO-loaded nanoethosomes on skin wrinkle improvement was studied by dermoscopic and histological examination on healthy humans and UV-irradiated rats, respectively. RESULTS: The optimized nanoethosomal formulation showed promising characteristics including narrow size distribution 0.17 ± 0.02, mean diameter of 98.9 ± 0.05 nm, EE% of 97.12 ± 3.62%, LC% of 13.87 ± 1.36% and zeta potential value of -15.1 ± 0.9 mV. The XRD results confirmed uniform drug dispersion in the nanoethosomes structure. In vitro and in vivo antioxidant studies confirmed the superior antioxidant effect of GO-loaded nanoethosomal formulation compared with control groups (blank nanoethosomes and GO suspension). CONCLUSIONS: Nanoethosomes was a promising carrier for dermal delivery of GO and consequently had superior anti-aging effect.

IL-4 induces the formation of multinucleated giant cells and expression of Beta5 integrin in central giant cell lesion

BACKGROUND: It is now well established that IL-4 has a central role in the development of monocytes to multinucleated giant cells (MGCs) by inducing the expression of integrins on the surface of monocytes. The aim of this study was to investigate the potential role of IL-4 in induction of β5 integrin expression in the peripheral blood samples of patients with giant cell granuloma. MATERIAL AND METHODS: Monocytes were isolated from peripheral blood samples of patients with central giant cell granuloma (CGCG) and healthy controls using human Monocyte Isolation Kit II. Isolated monocytes were then cultured in the absence or presence of IL-4 (10 and 20 ng/mL), and following RNA extraction and cDNA synthesis, Real-time PCR was performed to determine the level of β5 integrin expression. The formation of CGCGs and morphological analyses were done under light microscopy. For confirmation of CGCGs, immunocytochemistry technique was also carried out by anti-RANK (receptor-activator of NF-κB ligand) antibody. RESULTS: In both patient and control groups, β5 levels were significantly enhanced by increasing the IL-4 dose from 10 to 20 ng/mL. In addition, these differences were significant between patient and control groups without IL-4 treatment. On the other hand, the number of cells which expressed RANK and therefore the number of giant cells were significantly higher in the patient group in comparison to controls, as assessed by immunohistochemistry evaluations. CONCLUSIONS: In this study, we showed an elevation in the expression levels of β5 integrin when stimulated by IL-4. It is strongly indicated that this integrin acts as an important mediator during macrophage to macrophage fusion and development of giant cells

Histological evaluation of follicular delivery of arginine via nanostructured lipid carriers: a novel potential approach for the treatment of alopecia.

The use of lipidic nanoparticles can overcome the limitations of skin penetration of hydrophilic charged materials. Oleic acid as an ion pairing agent was used to enhance the encapsulation of positively charged arginine into lipophilic nanostructured lipid carrier (NLC). Histological study on the male hamsters was performed to assess the efficiency of drug delivery on hair growth. The accumulation of NLCs in the hair follicles was verified and in vivo studies showed more new hair follicle growth by utilizing arginine-loaded NLCs than arginine aqueous solution. It was concluded that employing ion pairing agent could enhance drug encapsulation into NLCs structure.

Dermal delivery of doxorubicin-loaded solid lipid nanoparticles for the treatment of skin cancer.

OBJECTIVE: Dermal delivery of Doxorubicin (Dox) would be an ideal way in maximising drug efficiency against skin cancer accompanying with minimising side effects. We investigated the potential of Dox-loaded Solid lipid nanoparticles (SLNs) for topical delivery against skin cancer. METHODS: In vitro and in vivo cytotoxicity of optimised formulation were evaluated on murine melanoma (B16F10) cells by MTT assay and melanoma induced Balb/C mice, respectively. Animal study followed by histological analysis. RESULTS: Optimised formulation showed mean particle size and encapsulation efficiency (EE) of 92 nm and 86% w/w (0.86% w/w value of encapsulated Dox in the lipid matrix), respectively. FTIR experiment confirmed drug-lipid interaction interpreting the observed high EE value for Dox. In vitro and in vivo results indicated the superiority of cytotoxic performance of Dox-loaded SLN compared to Dox solution. CONCLUSION: Our findings may open the possibilities for the topical delivery of Dox to the skin cancerous tissues.

Immunohistochemical evaluation of myofibroblast density in odontogenic cysts and tumors.

Background. The aim of this study was to investigate myofibroblast (MF) density in a broad spectrum of odontogenic cysts and tumors and the relation between the density of MFs and the clinical behavior of these lesions. Methods. A total of 105 cases of odontogenic lesions, including unicystic ameloblastoma (UAM), solid ameloblastoma (SA), odontogenic keratocyst (OKC), dentigerous cyst (DC), radicular cyst (RC) (15 for each category), and odontogenic myxoma (OM), adenomatoid odontogenic tumor (AOT), calcifying odontogenic cyst (COC) (10 for each category), were immunohistochemically stained with anti-α-smooth muscle actin antibody. The mean percentage of positive cells in 10 high-power fields was considered as MF density for each case. Results. A statistically significant difference was observed in the mean scores between the study groups (P < 0.001). The intensity of MFs was significantly higher in odontogenic tumors compared to odontogenic cysts (P < 0.001). There was no statistically significant difference between odontogenic tumors, except between UAM and OM (P = 0.041). The difference between OKC and odontogenic tumors was not statistically significant (P > 0.05). The number of MFs was significantly higher in OKC and lower in COC compared to other odontogenic cysts (P = 0.007 and P = 0.045, respectively). Conclusion. The results of the present study suggest a role for MFs in the aggressive behavior of odontogenic lesions. MFs may represent an important target of therapy, especially for aggressive odontogenic lesions. Our findings support the classification of OKC in the category of odontogenic tumors.

The Effect of Particle Size on the Deposition of Solid Lipid Nanoparticles in Different Skin Layers: A Histological Study.

PURPOSE: In the present study the effect of particle size, as a substantial parameters in skin penetration, on the deposition depth and rate of SLNs in different layers of skin was explored. METHODS: SLNs in different particle size ranges (80, 333 and 971 nm) made of Precirol as solid lipid were prepared using hot melt homogenization technique and pigmented by Rhodamine B to be able to be tracked in the skin under inspection of fluorescent microscopy. After 0.5 h, 3 h, 6 h and 24 h of SLNs administration on rat skin, animals were sacrificed and exercised skins were sliced by a freeze microtome. SLNs were monitored in the skin structure under fluorescence microscope. RESULTS: The size of SLNs played a crucial role in the penetration to deep skin layers. The sub100 nm size range of SLNs showed the most promising skin penetration rate and depth mainly via hair follicles. CONCLUSION: The results of the present study indicated that the selection of an appropriate size of particles may be a valuable factor impacting the therapeutic outcomes of dermal drug administration.

Evaluation of mast cell counts and microvessel density in reactive lesions of the oral cavity.

Background. Reliable immunohistochemical assays to assess the definitive role of mast cells (MCs) and angiogenesis in the pathogenesis of oral reactive lesions are generally not available. The aim of the present study was to evaluate mast cell counts (MCC) and microvessel density (MVD) in oral reactive lesions and determine the correlation between MCC and MVD. Methods. Seventy-five cases of reactive lesions of the oral cavity, including pyogenic granuloma, fibroma, peripheral giant cell granuloma, inflammatory fibrous hyperplasia, peripheral ossifying fibroma (15 for each category) were immunohisto-chemically stained with MC tryptase and CD31. Fifteen cases of normal gingival tissue were considered as the control group. The mean MCC and MVD in superficial and deep connective tissues were assessed and total MCC and MVD was computed for each lesion. Results . Statistically significant differences were observed in MCC and MVD between the study groups (P < 0.001). MC tryptase and CD31 expression increased in the superficial connective tissue of each lesion in comparison to the deep con-nective tissue. A significant negative correlation was not found between MCC and MVD in oral reactive lesions (P < 0.001, r = -0.458). Conclusion. Although MCs were present in the reactive lesions of the oral cavity, a direct correlation between MCC and MVD was not found in these lesions. Therefore, a significant interaction between MCs and endothelial cells and an active role for MCs in the growth of oral reactive lesions was not found in this study.

Histological assessment of follicular delivery of flutamide by solid lipid nanoparticles: potential tool for the treatment of androgenic alopecia.

CONTEXT: Flutamide is a potent anti-androgen with the several unwanted side effects in systemic administration, therefore, it has attracted special interest in the development of topically applied formulations for the treatment of androgenic alopecia. OBJECTIVE: The purpose of this study was to prepare and characterize the solid lipid nanoparticles (SLNs) of Flutamide for follicular targeting in the treatment of the androgenic alopecia. METHODS: Flutamide-loaded SLNs, promising drug carriers for topical application were prepared by hot melt homogenization method. Drug permeation and accumulation in the exercised rat skin and histological study on the male hamsters were performed to assess drug delivery efficiency in vitro and in vivo, respectively. RESULTS: The optimized Flutamide-loaded SLNs (size 198 nm, encapsulation efficiency percentage 65% and loading efficiency percentage 3.27%) exhibited a good stability during the period of at least 2 months. The results of X-ray diffraction showed Flutamide amorphous state confirming uniform drug dispersion in the SLNs structure. Higher skin drug deposition (1.75 times) of SLN formulation compared to Flutamide hydroalcoholic solution represented better localization of the drug in the skin. The in vivo studies showed more new hair follicle growth by utilizing Flutamide-loaded SLNs than Flutamide hydroalcoholic solution which could be due to the higher accumulation of SLNs in the hair follicles as well as slowly and continues release of the Flutamide through the SLNs maximizing hair follicle exposure by antiandrogenic drug. CONCLUSION: It was concluded Flutamide-loaded SLN formulation can be used as a promising colloidal drug carriers for topical administration of Flutamide in the treatment of androgenic alopecia.