Adipose-Derived Biogenic Nanoparticles for Suppression of Inflammation.

Extracellular vesicles secreted from adipose-derived mesenchymal stem cells (ADSCs) have therapeutic effects in inflammatory diseases. However, production of extracellular vesicles (EVs) from ADSCs is costly, inefficient, and time consuming. The anti-inflammatory properties of adipose tissue-derived EVs and other biogenic nanoparticles have not been explored. In this study, biogenic nanoparticles are obtained directly from lipoaspirate, an easily accessible and abundant source of biological material. Compared to ADSC-EVs, lipoaspirate nanoparticles (Lipo-NPs) take less time to process (hours compared to months) and cost less to produce (clinical-grade cell culture facilities are not required). The physicochemical characteristics and anti-inflammatory properties of Lipo-NPs are evaluated and compared to those of patient-matched ADSC-EVs. Moreover, guanabenz loading in Lipo-NPs is evaluated for enhanced anti-inflammatory effects. Apolipoprotein E and glycerolipids are enriched in Lipo-NPs compared to ADSC-EVs. Additionally, the uptake of Lipo-NPs in hepatocytes and macrophages is higher. Lipo-NPs and ADSC-EVs have comparable protective and anti-inflammatory effects. Specifically, Lipo-NPs reduce toll-like receptor 4-induced secretion of inflammatory cytokines in macrophages. Guanabenz-loaded Lipo-NPs further suppress inflammatory pathways, suggesting that this combination therapy can have promising applications for inflammatory diseases.

Organotropic drug delivery: Synthetic nanoparticles and extracellular vesicles.

Most clinically approved drugs (primarily small molecules or antibodies) are rapidly cleared from circulation and distribute throughout the body. As a consequence, only a small portion of the dose accumulates at the target site, leading to low efficacy and adverse side effects. Therefore, new delivery strategies are necessary to increase organ and tissue-specific delivery of therapeutic agents. Nanoparticles provide a promising approach for prolonging the circulation time and improving the biodistribution of drugs. However, nanoparticles display several limitations, such as clearance by the immune systems and impaired diffusion in the tissue microenvironment. To overcome common nanoparticle limitations various functionalization and targeting strategies have been proposed. This review will discuss synthetic nanoparticle and extracellular vesicle delivery strategies that exploit organ-specific features to enhance drug accumulation at the target site.

Extracellular vesicle-based drug delivery systems for cancer treatment.

Extracellular vesicles (EVs) are naturally occurring cell-secreted nanoparticles that play important roles in many physiological and pathological processes. EVs enable intercellular communication by serving as delivery vehicles for a wide range of endogenous cargo molecules, such as RNAs, proteins, carbohydrates, and lipids. EVs have also been found to display tissue tropism mediated by surface molecules, such as integrins and glycans, making them promising for drug delivery applications. Various methods can be used to load therapeutic agents into EVs, and additional modification strategies have been employed to prolong circulation and improve targeting. This review gives an overview of EV-based drug delivery strategies in cancer therapy.

Adipose-derived cellular and cell-derived regenerative therapies in dermatology and aesthetic rejuvenation.

Cellular and cell-derived components of adipose-derived tissue for the purposes of dermatologic and aesthetic rejuvenation applications have become increasingly studied and integrated into clinical practice. These components include micro-fragmented fat (nanofat), the stromal vascular fraction (SVF), adipose-derived mesenchymal stem cells (ASC), and extracellular vesicles (EVs), which have all shown capability to repair, regenerate, and rejuvenate surrounding tissue. Various aesthetic applications including hair growth, scar reduction, skin ischemia-reperfusion recovery, and facial rejuvenation are reviewed. In particular, results from preclinical and clinical studies are discussed, with a focus on clarification of nomenclature.

Gastrointestinal and renal excretion of potassium in African-Americans and White Americans.

OBJECTIVE: Several studies have confirmed the remarkable observation that cumulative urinary potassium (K(+)) excretion is less in African-Americans than White Americans even when identical amounts of potassium are provided in the diet. This study was designed to examine whether this decrease in urinary potassium could be compensatory to an increase in gastrointestinal excretion of potassium in African-Americans. METHODS: Twenty-three young, healthy, normotensive participants of both sexes and races were placed on a fixed diet of 100 mEq per day of K(+) and 180 mEq per day of sodium (Na(+)) for 9 days. All urine and stool were collected daily and analyzed for electrolytes. Blood was obtained for determination of electrolytes, blood urea nitrogen (BUN), creatinine, glucose, insulin, renin, and aldosterone at the beginning and at the end of the study period. RESULTS: Cumulative urinary excretion of K(+) was significantly less in African-Americans (609 ± 31 mEq) compared with White Americans (713 ± 22 mEq, P = 0.015). There was no significant racial difference, however, in the cumulative gastrointestinal excretion of K (105 ± 11 versus 95 ± 9 mEq, P = 0.28) in African-Americans versus White Americans, respectively. CONCLUSION: The racial difference in urinary K(+) handling manifested by decreased excretion of K(+) in African-Americans cannot be attributed to an increase in net gastrointestinal excretion of this cation.

Racial differences in potassium disposal.

BACKGROUND: African Americans appear relatively potassium (K(+))-deficient compared with Caucasian Americans whether on unregulated diets or on diets controlled for K(+) content. METHODS: To determine whether extrarenal K(+) disposal was affected by race, KCl (0.5 mEq/kg in 0.9% saline) was infused over 48 minutes to 12 African American and 12 Caucasian American normotensive, healthy subjects. Identical infusions were administered before and after 10 days of fixed electrolyte intake. In addition to serum K(+), glucose, insulin, renin, and aldosterone were measured in blood, and K(+) and sodium (Na(+)) in urine voided spontaneously during the infusions. Data were analyzed using a two-factor analysis of variance (ANOVA) with repeated measures. RESULTS: Basal serum K(+) did not differ between races (African American 3.97 +/- 0.06 mEq/L and Caucasian American 3.98 +/- 0.05, P= NS). The rise in serum K(+) during the infusion and the area under the curve of serum K(+) over the 3.5 hours of observation were both greater in African American (African American +0.82 +/- 0.07 mEq/L and Caucasian American +0.61 +/- 0.06, P= 0.001; and African American 6.9 +/- 0.5 units and Caucasian American 5.1 +/- 0.6, P= 0.0012). The 10-day period of controlled intake did not abolish these differences. Aldosterone at baseline was lower and insulin was higher in African Americans at the end of the infusion. Urinary K(+), plasma glucose, and renin levels did not differ between African Americans and Caucasian Americans. CONCLUSION: Disposal of an intravenous (iv) K(+) load is decreased in African Americans compared with Caucasian Americans, which may reflect decreased Na(+),K(+)-ATPase activity in African Americans in vivo.