Exosomes are cell-derived vesicles containing heterogeneous active biomolecules such as proteins, lipids, mRNAs, receptors, immune regulatory molecules, and nucleic acids. They typically range in ...size from 30 to 150 nm in diameter. An exosome’s surfaces can be bioengineered with antibodies, fluorescent dye, peptides, and tailored for small molecule and large active biologics. Exosomes have enormous potential as a drug delivery vehicle due to enhanced biocompatibility, excellent payload capability, and reduced immunogenicity compared to alternative polymeric-based carriers. Because of active targeting and specificity, exosomes are capable of delivering their cargo to exosome-recipient cells. Additionally, exosomes can potentially act as early stage disease diagnostic tools as the exosome carries various protein biomarkers associated with a specific disease. In this review, we summarize recent progress on exosome composition, biological characterization, and isolation techniques. Finally, we outline the exosome’s clinical applications and preclinical advancement to provide an outlook on the importance of exosomes for use in targeted drug delivery, biomarker study, and vaccine development.
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IJS, KILJ, NUK, PNG, UL, UM
Skin melanoma is one of the most common cancer types in the United States and worldwide, and its incidence continues to grow. Primary skin melanoma can be removed surgically when feasible and if ...detected at an early stage. Anti-cancer drugs can be applied topically to treat skin cancer lesions and used as an adjunct to surgery to prevent the recurrence of tumor growth. We developed a topical formulation composed of Navitoclax (NAVI), a BCL-2 inhibitor that results in apoptosis, and an ionic liquid of choline octanoate (COA) to treat early-stage melanoma. NAVI is a small hydrophobic molecule that solubilizes at 20% (w/v) when dissolved in 50% COA. Although NAVI is a highly effective chemotherapeutic, it is equally thrombocytopenic. We found that COA-mediated topical delivery of NAVI enhanced its penetration into the skin and held the drug in the deeper skin layers for an extended period. Topical delivery of NAVI produced a higher cancer-cell killing efficacy than orally administrated NAVI. In vivo experiments in a mouse model of human melanoma-induced skin cancer confirmed the formulation's effectiveness via an apoptotic mechanism without any significant skin irritation or systemic absorption of NAVI. Overall, this topical approach may provide a safe and effective option for better managing skin cancer in the clinic.
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•Ionic liquid solubilized the hydrophobic molecule Navitoclax (NAVI) without any solubilizer.•Combination of ionic liquid and NAVI form nano-structured micelles.•Facilitate transportation of the drug through the skin, tested in pig skin.•Minimize systemic circulation and maximize retention in dermis layer of skin.•The formulation induced apoptosis and provided a safe and potent topical delivery for the treatment of melanoma.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
An inkjet printed, biocompatible, heterostructure photodetector is described that was constructed using inks of photo-active molybdenum disulfide (MoS
2
) and electrically conducting ...graphene which facilitated charge collection of the photocarriers. The importance of such devices stems from their potential utility in age-related-macular degeneration, which is a condition where the photosensitive retinal tissue degrades with aging, eventually compromising vision. The absence of effective therapeutic remedies for patients with this disorder has motivated the development of such devices to restore some degree of visual function. Inkjet printed, flexible prosthetic devices offer design simplicity where additive manufacturing can enable large format, low-cost arrays. The biocompatible inkjet printed two-dimensional heterojunction devices were photoresponsive to broadband incoming radiation in the visible regime, and the photocurrent
I
ph
scaled proportionally with the incident light intensity, exhibiting a photoresponsivity
R
~ 0.30 A/W. This is 10
3
times higher compared to prior reports, and detectivity
D
was calculated to be ~3.6 × 10
10
Jones. Strain-dependent measurements were also conducted with bending, indicating the feasibility of such devices printed on flexible substrates. Drop cast and printed CT-MoS
2
inks were characterized using techniques, such as Raman spectroscopy, photoluminescence measurements and scanning electron microscopy. Both mouse embryonic fibroblast and human esophageal fibroblast were used for the biocompatibility analysis for inks drop cast on two types of flexible substrates, polyethylene terephthalate and polyimide. The biocompatibility of inks formed using two-dimensional graphene and MoS
2
on polyimide substrates was extremely high, in excess of 98% for mouse embryonic fibroblast.
Opportunistic fungal infections are responsible for over 1.5 million deaths per year. This has created a need for highly effective antifungal medication to be as potent as possible. In this study, we ...improved the efficacy of a common over the counter (OTC) antifungal skin medication, miconazole, by encapsulating nano-molecules of the drug in cholesterol/sodium oleate nano-vesicles. These nano-vesicles were characterized to optimize their size, zeta potential, polydispersity index and encapsulation efficiency. Furthermore, these nano-vesicles were compared to a conventional miconazole-based commercially available cream to determine potential improvements via permeation through the stratum corneum, cytotoxicity, and antifungal capabilities. Our results found that the vesicle size was within the nano range (~300 nm), with moderate polydispersity and stability. When compared with the commercially available cream, Actavis, as well as free miconazole, the miconazole nano-vesicle formulation displayed enhanced fungal inhibition by a factor of three or more when compared to free miconazole. Furthermore, with smaller nanoparticle (NP) sizes, higher percentages of miconazole may be delivered, further enhancing the efficacy of miconazole’s antifungal capability. Cytotoxicity studies conducted with human dermal fibroblast cells confirm its biosafety and biocompatibility, as cell survival rate was observed to be twofold higher in nano-vesicle formulation than free miconazole. This formulation has the potential to treat fungal infections through increasing the retention time in the skin, improving the treatment approach, and by enhancing the efficacy via the use of nano-vesicles.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The rapidly growing field of tissue engineering hopes to soon address the shortage of transplantable tissues, allowing for precise control and fabrication that could be made for each specific ...patient. The protocols currently in place to print large-scale tissues have yet to address the main challenge of nutritional deficiencies in the central areas of the engineered tissue, causing necrosis deep within and rendering it ineffective. Bioprinted microvasculature has been proposed to encourage angiogenesis and facilitate the mobility of oxygen and nutrients throughout the engineered tissue. An implant made via an inkjet printing process containing human microvascular endothelial cells was placed in both B17-SCID and NSG-SGM3 animal models to determine the rate of angiogenesis and degree of cell survival. The implantable tissues were made using a combination of alginate and gelatin type B; all implants were printed via previously published procedures using a modified HP inkjet printer. Histopathological results show a dramatic increase in the average microvasculature formation for mice that received the printed constructs within the implant area when compared to the manual and control implants, indicating inkjet bioprinting technology can be effectively used for vascularization of engineered tissues.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Exosomes are cell-derived vesicles containing heterogeneous active biomolecules such as proteins, lipids, mRNAs, receptors, immune regulatory molecules, and nucleic acids. They are typically range in ...size 30–150 nm in diameter. An exosome’s surfaces can be bioengineered with antibodies, fluorescent dye, peptides, and tailored for small molecule and large active biologics. Exosomes have enormous potential as a drug delivery vehicle due to enhanced biocompatibility, excellent payload capability, and reduced immunogenicity compared to alternative polymeric-based carriers. Due to active targeting and specificity, exosomes are capable of delivering their cargo to exosome-recipient cells. Additionally, exosomes can potentially act as early-stage disease diagnostic tools as the exosome carries various protein biomarkers associated with a specific disease. In this review, we summarized recent progress on exosome composition, biological characterization, and isolation techniques. Finally, we have outlined the exosome’s clinical applications and preclinical advancement to provide an outlook on the importance of exosomes for use in targeted drug delivery, biomarker study, and vaccine development.
The exosome is a bio-inspired and biomimetic material consisting of proteins, lipids, and other various cellular derivatives and has potential as a therapeutic and diagnostic tool. Due to its vast biocompatibility and origin from biological cells, the exosome has many advantages over synthetic and semi-synthetic polymeric biomaterials used in biomedical applications.
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IJS, KILJ, NUK, PNG, UL, UM
Two-dimensional (2D) layered materials have shown promise for a wide range of semiconducting devices which can be formed not only on rigid Si substrates but also low-cost, flexible and biocompatible ...substrates. In this paper, we have tested the biocompatibility of various 2D materials, such as graphene and MoS 2 in several organic solvents. Specifically, these materials have been dispersed in Isopropyl Alcohol (IPA), a mixture of Cyclohexanone/Terpineol with a 7:3 ratios (C/T), and N-Methyl-2-pyrrolidone (NMP). The electrical properties were characterized of all drop cast solutions. For preliminary analysis of the electrically-conducting dispersions of graphene and MoS 2 , the solutions were drop cast onto thin, flexible and polyethylene terephthalate (PET) and polyimide films. Mouse embryonic fibroblast cells (STOs) were used to perform biocompatibility assays. Optical microscopy was used to gauge the degree of biocompatibility of all of the formulated dispersions. We also highlighted an inkjet printed photodetector which can be considered as a future possibility for in vivo photo sensing applications.
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