Harnessing tumor-derived exosomes: A promising approach for the expansion of clinical diagnosis, prognosis, and therapeutic outcome of prostate cancer.

Prostate cancer is the second leading cause of men's death worldwide. Although early diagnosis and therapy for localized prostate cancer have improved, the majority of men with metastatic disease die from prostate cancer annually. Therefore, identification of the cellular-molecular mechanisms underlying the progression of prostate cancer is essential for overcoming controlled proliferation, invasion, and metastasis. Exosomes are small extracellular vesicles that mediate most cells' interactions and contain membrane proteins, cytosolic and nuclear proteins, extracellular matrix proteins, lipids, metabolites, and nucleic acids. Exosomes play an essential role in paracrine pathways, potentially influencing Prostate cancer progression through a wide variety of mechanisms. In the present review, we outline and discuss recent progress in our understanding of the role of exosomes in the Prostate cancer microenvironment, like their involvement in prostate cancer occurrence, progression, angiogenesis, epithelial-mesenchymal transition, metastasis, and drug resistance. We also present the latest findings regarding the function of exosomes as biomarkers, direct therapeutic targets in prostate cancer, and the challenges and advantages associated with using exosomes as natural carriers and in exosome-based immunotherapy. These findings are a promising avenue for the expansion of potential clinical approaches.

Anticancer Effect of Enterococcus faecium, Isolated from Vaginal Fluid, on Ovarian Cancer Cells

Background: Given the association between cervicovaginal microbiota and OVC, we investigated the effect of Enterococcus faecium conditioned medium (CM) on OVC (Caov-4) cells. Methods: CM was obtained from the bacterium E. faecium isolated from the vagina of healthy women. The Caov-4 cells were treated with varying concentrations of CM that comprised co-cultured bacteria with 0.2, 0.5, 1, 1.5, and 2 OD for 12, 24, and 48 h. The apoptosis and growth of cancer cells were evaluated by 4',6-diamidino-2-phenylindole (DAPI) staining, flow cytometry, and DNA laddering assay. Moreover, the expression of PTEN, BAX, BCL2, and AKT1 genes were analyzed using real-time PCR. Results: The CM at a concentration of 0.5 OD from the cultured bacteria and incubation time of 48 h showed the highest negative effect on the viability of cancer cells. The CM treatment increased DNA fragmentation and also induced apoptosis in Caov-4 cells. Interestingly, CM could decrease the expression of proapoptotic genes were less, while antiapoptotic genes were more than fluorouracil in the presence of CM. Conclusion: CM of human-derived E. faecium could have an anticancer effect on OVC cells in a concentration- and time-dependent manner. This study demonstrated that E. faecium secretes anticancer substances into the CM, which could directly affect the viability and apoptosis of cancer cells.

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.

Nanogel Containing Gamma-Oryzanol-Loaded Nanostructured Lipid Carriers and TiO2/MBBT: A Synergistic Nanotechnological Approach of Potent Natural Antioxidants and Nanosized UV Filters for Skin Protection.

The human skin is a recurring target of external aggressions, such as UV radiation, leading to exacerbation of the aging process and the occurrence of skin diseases, such as cancer. Hence, preventive measures should be taken to protect it against these aggressions, consequently decreasing the chance of disease development. In the present study, a topical xanthan gum nanogel containing gamma-oryzanol-loaded nanostructured lipid carriers (NLCs) and nanosized UV filters TiO2 and methylene bis-benzotriazolyl tetramethylbutylphenol (MBBT) was developed to assess their synergistic potential in having multifunctional skin beneficial properties. The developed NLCs contained the natural-based solid lipids shea butter and beeswax, liquid lipid carrot seed oil, and the potent antioxidant gamma-oryzanol, with an optimum particle size for topical application (<150 nm), good homogeneity (PDI = 0.216), high zeta potential (-34.9 mV), suitable pH value (6), good physical stability, high encapsulation efficiency (90%), and controlled release. The final formulation, a nanogel containing the developed NLCs and the nano UV filters, showed high long-term storage stability and high photoprotection ability (SPF = 34) and resulted in no skin irritation or sensitization (rat model). Hence, the developed formulation showed good skin protection and compatibility, demonstrating promise as a new platform for the future generation of natural-based cosmeceuticals.

Recent advances in pain management based on nanoparticle technologies.

BACKGROUND: Pain is a vital sense that indicates the risk of injury at a particular body part. Successful control of pain is the principal aspect in medical treatment. In recent years, the advances of nanotechnology in pain management have been remarkable. In this review, we focus on literature and published data that reveal various applications of nanotechnology in acute and chronic pain management. METHODS: The presented content is based on information collected through pain management publications (227 articles up to April 2021) provided by Web of Science, PubMed, Scopus and Google Scholar services. RESULTS: A comprehensive study of the articles revealed that nanotechnology-based drug delivery has provided acceptable results in pain control, limiting the side effects and increasing the efficacy of analgesic drugs. Besides the ability of nanotechnology to deliver drugs, sophisticated nanosystems have been designed to enhance imaging and diagnostics, which help in rapid diagnosis of diseases and have a significant impact on controlling pain. Furthermore, with the development of various tools, nanotechnology can accurately measure pain and use these measurements to display the efficiency of different interventions. CONCLUSIONS: Nanotechnology has started a new era in the pain management and many promising results have been achieved in this regard. Nevertheless, there is still no substantial and adequate act of nanotechnology in this field. Therefore, efforts should be directed to broad investigations.

Optimization of Influential Variables in the Development of Buprenorphine and Bupivacaine Loaded Invasome for Dermal Delivery.

Purpose: Hydrophilic drugs are extensively applied in clinical applications. Inadequate dermal penetration of these drugs is a great challenge. Incorporation of drugs into nano-carrier systems overcomes lower penetration drawbacks. Invasomes are novel nano-carrier systems which enhance transdermal penetration by using terpene and ethanol in their structures. buprenorphine and bupivacaine hydrochlorides are two potent analgesic drugs that are loaded simultaneously in the nano-invasome structure as opioid and non-opioid drugs. Methods: The full factorial experimental design was used for planning and estimating optimum formulations of invasome systems. Three influential factors like terpene type, terpene concentration and preparation method were comprehensively analyzed for achieving high encapsulation efficiency (EE) and optimum size. Results: The mean sizes of designed invasomes were in the range of 0.39-5.86 µm and high values of EE and loading capacity (LC) were reported as 98.77 and 19.75 for buprenorphine-loaded invasome, respectively. Zeta potential measurements confirmed that the obtained high value of EE might be as a result of reversible ionic interactions between positively charged drugs and negatively charged phospholipidic part of invasome structure. Another characterization of the prepared formulations was carried out by Fourier transform infrared (FTIR), X-ray diffraction (XRD) and dynamic light scattering (DLS) technique. Conclusion: The satisfactory obtained results of formulations encourage researchers to get optimum topical analgesic formulations with potent and rapid onset time properties required in invasive cutaneous procedures.

An overview of various treatment strategies, especially tissue engineering for damaged articular cartilage.

Many traditional procedures, including surgical methods such as microfracture of subchondral bone and soft tissue transplantation, have been widely used to treat damaged cartilage. However, there is still no definitive cure for cartilage defects. In recent decades, tissue engineering has raised hopes for the repair of defective cartilage. Different approaches are used for cartilage engineering, in which cells, scaffolds, and biological signals or growth factors may be used alone or in combination. Additionally, the imitation of the mechanical properties of the natural cartilage tissue by bioreactors is also helpful in this regard. It should be noted that in the transplantation of engineered cartilage tissue, there are challenges such as poor integration, inflammation and phenotypic instability that may lead to failure of neo-cartilage transplantation. Therefore, a comprehensive understanding of the multiple therapeutic approaches, including surgical procedures, cell-based methods and tissue engineering, should be obtained. The present review article provides this information, along with a variety of factors, including cells, materials, and biological/biomechanical factors required for the engineering of cartilage tissue, as well as the challenges ahead and their solutions.

Invasome: A Novel Nanocarrier for Transdermal Drug Delivery.

Invasomes are novel vesicular systems that exhibit improved transdermal penetration compared to conventional liposomes. These vesicles contain phospholipids, ethanol, and terpene in their structures; these components confer suitable transdermal penetration properties to the soft vesicles. The main advantages of these nanovesicles lie in their ability to increase the permeability of the drug into the skin and decrease absorption into the systemic circulation, thus, limiting the activity of various drugs within the skin layer. In this paper, several features of invasomes, including their structure, mechanism of penetration, applications, characterization, and potential advantages in dermal drug delivery, are highlighted. Overall, this review suggests that enhanced transdermal penetration of drugs using invasomes provides an appropriate opportunity for the development of lipid vesicular carriers.

Nanoethosomes for Dermal Delivery of Lidocaine.

PURPOSE: It is necessary for local anesthetics to pass through the stratum corneum to provide rapid pain relief. Many techniques have been reported to enhance intradermal penetration of local anesthetics such as vesicular lipid carriers. Ethosomes are lipid vesicles containing phospholipids, ethanol at relatively high concentration. We hypothesized that synergistic effects of phospholipids and high concentration of ethanol in formulation could accelerate penetration of nanoethosomes in deep layers of skin. METHODS: Lidocaine-loaded nanoethosomes were prepared and characterized by size and zeta analyzer, scanning electron microscopy (SEM) and X-ray diffractometer (XRD). Furthermore, encapsulation efficiency (EE), loading capacity (LC), and skin penetration capability were evaluated by in vitro and in vivo experiments. RESULTS: results showed that the particle size, zeta potential, EE and LC of optimum formulation were 105.4 ± 7.9 nm, -33.6 ± 2.4 mV, 40.14 ± 2.5 %, and 8.02 ± 0.71 respectively. SEM results confirmed the non-aggregated nano-scale size of prepared nanoethosomes. Particle size of ethosomes and EE of Lidocaine were depended on the phospholipid and ethanol concentrations. XRD results demonstrated the drug encapsulation in amorphous status interpreting the achieved high drug EE and LC values. In vitro and in vivo assays confirmed the appropriate skin penetration of Lidocaine with the aid of nanoethosomes and existence of deposition of nanoethosomes in deep skin layers, respectively. CONCLUSION: The developed nanoethosomes are proposed as a suitable carrier for topical delivery of anesthetics such as Lidocaine.