ABSTRACT
A rapidly growing body of experimental evidence has begun to shed light on the wide ranging molecular mechanisms which modulate intra- and inter-cellular communications. A substantial quantity of the available knowledge has only been uncovered in recent years, and we are learning that donor cells release nanovesicles, known as exosomes, which regulate the cellular behavior of recipient cells following uptake. Based on the impressive capacity of exosomes in delivering their "payload", different therapeutic agents, are currently being tested using this delivery method for more effective therapy. This review summarizes the most recent developments in exosome bioactivities and discusses the biochemical nature of exosomes and their biogenesis. It also summarizes the use of exosomes as delivery vehicles for drugs and natural compounds to the targeted site.
Subject(s)
Drug Delivery Systems , Exosomes , Phytochemicals , Animals , Curcumin , Humans , Mice , Models, BiologicalABSTRACT
A Ficus umbellata is used to treat cancer. The present work was therefore designed to assess antitumor potentials of F. umbellata extracts in nine different cell lines. Cell cycle, apoptosis, cell migration/invasion, levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), caspases activities as well as Bcl-2 and Bcl-xL protein content were assessed in MDA-MB-231 cells. The 7,12-dimethylbenz(a)anthracene (DMBA)-induced carcinogenesis in rats were also used to investigate antitumor potential of F. umbellata extracts. The F. umbellata methanol extract exhibited a CC50 of 180 µg/mL in MDA-MB-231 cells after 24 h. It induced apoptosis in MCF-7 and MDA-MB-231 cells, while it did not alter their cell cycle phases. Further, it induced a decrease in MMP, an increase in ROS levels and caspases activities as well as a downregulation in Bcl-2 and Bcl-xL protein contents in MDA-MB-231 cells. In vivo, F. umbellata aqueous (200 mg/kg) and methanol (50 mg/kg) extracts significantly (p < 0.001) reduced ovarian tumor incidence (10%), total tumor burden (58% and 46%, respectively), average tumor weight (57.8% and 45.6%, respectively) as compared to DMBA control group. These results suggest antitumor potential of F. umbellata constituents possibly due to apoptosis induction mediated through ROS-dependent mitochondrial pathway.
Subject(s)
Ficus/chemistry , Plant Bark/chemistry , Plant Extracts/therapeutic use , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Female , Humans , Mitochondria/metabolism , Plant Extracts/chemistry , Rats , Rats, Wistar , Reactive Oxygen Species/metabolism , bcl-X Protein/metabolismABSTRACT
The pharmacokinetics of Amphotericin B (AmB) from polyethylene glycol 2000 (PEG 2000) entrapped cross-linked bovine serum albumin (BSA) microsphere formulations were investigated and compared with solution formulation. The microsphere preparations were characterized for particle size using electron microscopy, zeta potential and encapsulation efficiency. The microsphere formulations demonstrated a sustained release of AmB for a longer period of time, with no rise in plasma creatinine and potassium levels. The enhanced AmB accumulation in lungs was observed which could be of importance since lungs are the primary target in most fungal infections. The stealth property of submicron cross-linked BSA microspheres in formulations containing PEG 2000 (formulation F-2N) and without PEG 2000 (formulation F-1N) was also evaluated. There was no evidence that microspheres embedded with PEG remained longer in circulation; however, it was noticed that the internalization of formulation F-2N microspheres was delayed when compared with microspheres from formulation F-1N.
