Cyclodextrins as an encapsulation molecular strategy for volatile organic compounds- Pharmaceutical applications.

The use of essential oils has gained importance due to their wide range of biological properties. Essential oils comprise a complex mixture of volatile organic compounds (VOCs), so the study of VOCs as active pharmaceutical ingredients is often more precise and fruitful. VOCs are natural origin molecules that constitute a sustainable alternative to synthetic drugs due to their important therapeutic value. However, VOCs possess poor solubility in aqueous solutions, high volatility, and, consequently, low stability and bioavailability, limiting VOC handling in industry and their potential use in therapeutics, despite their promising biological properties. Thereby, cyclodextrins (CDs) have emerged as suitable carriers of VOCs, giving rise to so-called VOC/CD inclusion complexes. CDs constitute an inexpensive viable solution for encapsulating VOCs to improve their properties, namely their apparent solubility and stability toward pH, light, and temperature. This review provides a conceptual framework of several VOC/CD inclusion complexes developed. In addition, the most exploited preparation techniques and their influence on the values of encapsulation efficiency and formation constant (Kf) are highlighted. The most recent in vitro or in vivo biological experiments regarding VOC/CD inclusion complexes in the development of pharmaceutical products are also presented. Finally, the toxicological, and regulatory aspects are discussed.

Co-Delivery of erlotinib and resveratrol via nanostructured lipid Carriers: A synergistically promising approach for cell proliferation prevention and ROS-Mediated apoptosis activation.

Cancer treatments are always associated with various challenges, and scientists are constantly trying to find new therapies and methods. Erlotinib (ELT) is a well-known medicine against non-small cell lung cancer (NSCLC). However, treatments by ELT disrupt therapy due to drug resistance and pose severe challenges to patients. To achieve high-performance treatment, we gained nanostructured lipid carriers (NLCs) to evaluate synergistic anticancer effects of co-delivery of ELT and resveratrol (RES), a natural herbal derived phenol against NSCLC. NLCs are prepared via the hot homogenization method and characterized. In vitro cytotoxicity of formulations were evaluated on adenocarcinoma human alveolar basal epithelial (A549) cells. Prepared NLCs showed a narrow particle size (97.52 ± 17.14 nm), negative zeta potential (-7.67 ± 4.55 mV), and high encapsulation efficiency (EE%) was measured for the prepared co-delivery system (EE% 89.5 ± 5.16 % for ELT and 90.1 ± 6.61 % for RES). In vitro outcomes from cell viability study (12.63 % after 48 h of treatment), apoptosis assay (85.50%.), cell cycle (40.00% arrest in G2-M), and western blotting investigations (decreasing of protein expression levels of survivin, Bcl-2, P-Caspase 3P-caspase 9, and P-ERK 1/2, and additionally, increasing protein levels of BAX, P53, C-Caspase 3 and 9), DAPI staining, and colony formation assays showed the augment cytotoxic performances for co-delivery of ELT and RES loaded NLCs. Our study introduced the co-delivery of ELT and RES by NLCs as a novel strategy to elevate the efficacy of chemotherapeutics for NSCLC.

Nanocarrier-based dermopharmaceutical formulations for the topical management of atopic dermatitis.

Atopic dermatitis (AD) is a chronic disease that affects the skin, and that is characterized by highly itchy inflammation, frequent eczematous lesions, and a fluctuating course. The current treatment consists of a multi-stage approach that aims to establish persistent disease control towards the improvement of the quality of life of the patients. Topical therapy is the basis of AD treatment, however, due to the difficulty of crossing the skin barrier, topical application of drugs remains a challenge. In fact, in addition to the low skin bioavailability, and limited accessibility to deeper skin of the drugs - due to difficulty in penetrating the epidermis - implemented drugs in the clinical are associated with serious adverse effects, which are responsible for safety and efficacy limitations, leading to a reduction in patients' compliance. Nanotechnology arises as an emerging approach for the treatment of AD, allowing for controlled release, targeted delivery, improved penetration, and bioavailability of drugs assets, resulting in marked improved therapeutic efficacy and reduction of adverse effects. Although its promising outputs, additional studies are needed to recognize the toxicological characteristics, cost-benefit, and long-term safety of nanocarriers applied to this end. Advanced drug delivery systems, particularly nanoemulsions, liposomes, ethosomes, transfersomes, solid lipid nanoparticles, nanostructured lipid carriers, nanocrystals, polymeric nanoparticles, and polymeric micelles have been used, and are thoroughly addressed in this review as promising nanoformulations towards the topical treatment of AD.

Prevention of UV-induced skin cancer in mice by gamma oryzanol-loaded nanoethosomes.

AIMS: Skin cancer is the most widespread cancer worldwide, mainly caused by exposure to ultraviolet radiation (UV) in sunlight. Utilizing topical preventive agents in routinely daily used cosmetics may prevent UV-related skin damages and skin cancers. γ-Oryzanol (GO) is a natural component derived from rice bran oil, with potential antioxidant and skin anti-aging properties. MAIN METHODS: We biologically thorough studied the antioxidant and anticancer effects of GO in vitro to found the effective signaling pathways, then evaluated the sun protection factor of prepared formulation, and finally investigated the long-term preventive effects of GO-loaded nanoethosomes (GO-NEs) against UVB-induced skin cancer in mice. KEY FINDINGS: GO-NEs could effectively prevent UVB-induced skin cancer. SIGNIFICANCE: Our results suggest that GO-NEs could be utilized as an innovative ingredient in cosmetics.

Ethosomes as Nanocarriers for the Development of Skin Delivery Formulations.

The use of nanotechnology has been extensively explored for developing efficient drug delivery systems towards topical and transdermal applications. Ethosomes constitute a vesicular nanocarrier containing a relatively high concentration of ethanol (20-45%). Ethanol is a well-known permeation enhancer, which confers ethosomes unique features, including high elasticity and deformability, allowing them to penetrate deeply across the skin and enhance drug permeation and deposition. The improved composition of ethosomes offer, thereby, significant advantages in the delivery of therapeutic agents over particularly the conventional liposomes regarding different pathologies, including acne, psoriasis, alopecia, skin infections, hormonal deficiencies, among others. This review provides a comprehensive overview of the ethosomal system and an assessment of its potential as an efficient nanocarrier towards the skin delivery of active ingredients. Special attention is given to the composition of ethosomes and the mechanism of skin permeation, as well as their potential applications in different pathologies, particularly skin pathologies (acne, psoriasis, atopic dermatitis, skin cancer and skin infections). Some examples of ethosome-based formulations for the management of skin disorders are also highlighted. Besides the need for further studies, particularly in humans, ethosomal-based formulations hold great promise in the skin delivery of active ingredients, which increasingly asserts oneself as a viable alternative to the oral route.

Plant-mediated green synthesis of metal-based nanoparticles for dermopharmaceutical and cosmetic applications.

The skin is the primordial barrier that protects the human body against environmental factors. Due to the arise of dermatological pathologies, the development of efficient delivery systems for topical applications has received increased interest. The highest challenge consists of increasing the penetration of the active ingredients through the skin barrier, alongside to the need of obtaining enough skin retention to achieve therapeutic concentrations. Metals, specially noble metals, have been used for years to treat and prevent health issues, among them dermatological disorders. Nanoparticles have been extensively used for topical applications given their advantages, namely by enhancing solubility of apolar drugs, the possibility of controlled release, the higher stability and the capability to target specific areas and delivery of high concentrations of active ingredients. In order to take advantage of the before mentioned unique properties of nanoparticles and the biological activities of metals, various metal-based nanoparticles (MNPs) have been synthesized in the past few years, such as silver (AgNPs), gold (AuNPs), zinc (ZnNPs), zinc oxide (ZnONPs), copper (CuNPs) and copper oxide (CuONPs) nanoparticles. These MNPs are flexible structures that allow the control of physical characteristics, with enhanced surface properties, which provides a high applicability in dermopharmacy and cosmetics. The conventional methods for synthesizing nanoparticles (physical and chemical approaches) are associated with major drawbacks, being the most concerning the high cost (in resources, energy, time and space) and human/environmental toxicity. Hence, the need to develop an alternative synthesis pathway was imposed, giving rise to the green synthesis methodology. In general, green synthesis consist of using biological sources (plants, bacteria or fungi) to synthesize ecological benign, non-hazard and biocompatible nanoparticles. With the development of green synthesis, starting materials have been used more frequently, among them plants. Plant-mediated green synthesis of nanoparticles is based on the use of plant extracts to synthesize nanoparticles, and their outstanding advantages have paved the way for exciting developments on nanoparticle synthesis to the detriment of complex and toxicity-associated chemical and physical synthesis. MNPs produced by plant-mediated synthesis also demonstrate notorious biological activities, i.e., anticancer, antioxidant, anti-inflammatory, antimicrobial, wound healing and antiaging activities. However, safety assessment of phyto MNPs (phyto-MNPs) holds significant importance due to the lack of toxicological studies and the conception issues that some of the available studies show. In general, current studies suggest the biocompatibility and safety of phyto-MNPs, together with significantly improved and relevant biological activities towards dermopharmaceutical and cosmetic applications. Against this backdrop, there is still a long way to run until the application of phyto-MNPs in the medical, pharmaceutical and cosmetic fields, but studies so far show a very high potential towards their clinical translation for dermopharmaceutical and cosmetics applications. This review focuses on phyto-MNPs synthesized resorting to various plant extracts, including their production, characterization and the biological activities that support their topical application for dermopharmaceutical and cosmetic purposes.

Nanovehicles for co-delivery of anticancer agents.

Effective cancer treatment remains a significant challenge in human healthcare. Although many different types of cancer therapy have been tested, scientists have now concluded that combinations of drugs, or drugs plus gene therapy, can target multiple pathways to fight cancer. Nanovehicles can increase drug uptake inside tumor cells, improve biodistribution and accumulation at tumor sites. The ability to deliver two or more anticancer drugs, genes, among others, at the same time and place will increase therapeutic effects while decreasing side effects and reducing the risk of multidrug resistance. This review discusses the advantages of nano-based co-delivery methods in cancer therapy, summarizes the common types of nanovehicles and their preparation methods, and covers some recent co-delivery studies in detail.

Limitations of Spinal Anesthesia for Patient and Surgeon During Percutaneous Nephrolithotomy.

PURPOSE: To evaluate the intraoperative pain score of patients who undergo percutaneous nephrolithotomy under spinal anesthesia and to evaluate surgeons' and patients' convenience with this type of anesthesia. MATERIALS AND METHODS: PCNL cases who were performed by two endourology fellows under spinal anesthesia during June to July 2014 were included. Spinal anesthesia was performed using injection of 0.25mg/kg bupivacaine 0.5% in the intrathecal space. All procedures were performed with the patient in the prone position. Stone access was made by using ?uoroscopic guidance, and the tract was dilated using a single-stage technique. Visual analogue pain score was used to assess patients' pain during operation, immediately after, and 2 hours later. RESULTS: 50 patients were enrolled during the study period. Visual analogue pain score of 10 and 8 were observed in 5 and three patients respectively. In two patients the operation was terminated because of patient anxiety and pain. In another patient a second access was not obtained to remove a staghorn stone because of patient's agitation. Gross agitation was observed in six patients. Apart from flank pain, intraoperative pain was felt in the flank, scapula, abdomen and/or chest. CONCLUSION: Spinal anesthesia does not provide enough analgesia for the patient in a limited frequency of percutaneous nephrolithotomy operations. We could not find statistically significant predictors of insufficient analgesiabased on patients' demographics, stone characteristics or access location.

Nano-Phytosome: A Developing Platform for Herbal Anti-Cancer Agents in Cancer Therapy.

BACKGROUND: Cancer is one of the main causes of death in the world. It has not yet been cured in an efficient manner and has remained a major challenge for current chemotherapy. OBJECTIVE: This review summarizes the latest investigations regarding the possible application of phytosome complexes for cancer therapy, their formulation techniques, and mechanism of transportation through phytosome. RESULTS: Nanotechnology opened a pioneer field in cancer therapy by modifying significant properties of drugs and their carriers. Nanotechnology utilizes various nanostructures to transport anti-cancer agents to the site of action. The greater stability of nanophytosomes is due to formation of chemical links between phospholipid molecules and phytoactive agents. Among several new drug delivery systems, phytosomes depict an advanced technology to deliver phytoactive compounds to the target site of action, and at present, several phytosome formulations are in clinical use. CONCLUSION: Potential anti-cancer properties of phytoconstituents are enhanced by phytosomal formulations.

Bilateral Laparoscopic Stone Surgery for Renal Stones- A Case Series.

PURPOSE: To present our experience with synchronous or metachronous laparoscopic pyelolithotomy and ureterolithotomy for patients with bilateral urolithiasis. MATERIALS AND METHODS: The data of all patients who underwent laparoscopic pyelolithotomy (± ureterolithotomy) for bilateral renal and/or ureteral stones from November 2009 to July 2014 were included. Laparoscopic operations were performed through a transperitoneal approach. RESULTS: 10 patients underwent laparoscopic operations for renal stones (19 kidney stones) and ureteral stones (1 ureteral stone). 4 patients underwent synchronous operations and 6 patients underwent metachronous operations. The mean ± SD of operation duration were 212 ± 51 minutes for synchronous operations and 166 ± 41 minutes for metachronous operations. Residual stone was observed 5 patients. No patient developed urinary leakage. CONCLUSION: Laparoscopic pyelolithotomy and/or ureterolithotomy for bilateral stones is a feasible option in centers with experience in laparoscopy.

X-Ray Free Minimally Invasive Surgery for Urolithiasis in Pregnancy.

PURPOSE: Our goal was to present our experience with ultrasound guided supine or prone percutaneous nephrolithotomy in three pregnant women under spinal anesthesia. MATERIALS AND METHODS: Three pregnant women in the 16th, 20th and 28th weeks of pregnancy presented with symptomatic large renal stone in the first patient and multiple renal stones in the second and third patients which were unresponsive to conventional medical therapy. They requested a definitive stone treatment. The operations were done in November 2012, June 2014 and February 2015. Data was gathered prospectively. All steps of gaining access to the pyelocalyceal system including needle insertion, tract dilation, and Amplatz sheath placement were performed under ultrasonography guidance. Tract was dilated with a single shot technique. The first two procedures were performed in supine position and the third procedure was performed in lateral flank position. RESULTS: Two patients were stone-free postoperatively and one patient had only an asymptomatic 4 mm residual stone. They were discharged on the 2nd postoperative day and had an uneventful postoperative course. No fever, bleeding or renal colic was noticed during postoperative hospitalization. All patients delivered their fetuses at term without any abnormality reported by the examining pediatric specialist after their birth. CONCLUSION: Ultrasonography can be used as an imaging modality guiding all steps of obtaining percutaneous access in pregnant women. Supine or flank ultrasound guided percutaneous nephrolithotomy can be offered to pregnant women in whom conservative measures fail to the patients' wellbeing.