The encapsulation of miR-34a into chitosan/PLGA nanoparticles in order to obtain nanoplexes useful for the modulation of the biopharmaceutical features of the active compound was studied. The nanoplexes were obtained through nanoprecipitation and were characterized by a mean diameter of ~160 nm, a good size distribution and a positive surface charge. The structure of the nanoparticles allowed a high level of entrapment efficiency of the miR-34a and provided protection of the genetic material from the effects of RNase. A high degree of transfection efficiency of the nanoplexes and a significant in vitro antitumor effect against multiple myeloma cells was demonstrated. The therapeutic properties of the nanoplexes were evaluated in vivo against human multiple myeloma xenografts in NOD-SCID mice. The systemic injection of miR-34a mimic-loaded nanoparticles significantly inhibited tumor growth and translated into improved survival of the laboratory mice. RT-PCR analysis carried out on retrieved tumors demonstrated the presence of a high concentration of miR-34a mimics. The integrity of the nanoplexes remained intact and no organ toxicity was observed in treated animals.
Sulforaphane is a multi-action drug and its anticancer activity is the reason for the continuous growth of attention being paid to this drug. Sulforaphane shows an in vitro antiproliferative activity against melanoma and other skin cancer diseases. Unfortunately, this natural compound cannot be applied in free form on the skin due to its poor percutaneous permeation determined by its physico-chemical characteristics. The aim of this investigation was to evaluate ethosomes® and transfersomes® as ultradeformable vesicular carriers for the percutaneous delivery of sulforaphane to be used for the treatment of skin cancer diseases. The physico-chemical features of the ultradeformable vesicles were evaluated. Namely, ethosomes® and transfersomes® had mean sizes <400 nm and a polydispersity index close to 0. The stability studies demonstrated that the most suitable ultradeformable vesicles to be used as topical carriers of sulforaphane were ethosomes® made up of ethanol 40% (w/v) and phospholipon 90G 2% (w/v). In particular, in vitro studies of percutaneous permeation through human stratum corneum and epidermis membranes showed an increase of the percutaneous permeation of sulforaphane. The antiproliferative activity of sulforaphane-loaded ethosomes® was tested on SK-MEL 28 and improved anticancer activity was observed in comparison with the free drug.
Joint diseases are one of the most common causes of morbidity
and
disability worldwide. The main diseases that affect joint cartilage
are osteoarthritis and rheumatoid arthritis, which require chronic
treatment focused on symptomatic relief. Conventional drugs administered
through systemic or intra-articular routes have low accumulation and/or
retention in articular cartilage, causing dose-limiting toxicities
and reduced efficacy. Therefore, there is an urgent need to develop
improved strategies for drug delivery, in particular, the use of micro-
and nanotechnology-based methods. Encapsulation of therapeutic agents
in delivery systems reduces drug efflux from the joint and protects
against rapid cellular and enzymatic clearance following intra-articular
injection. Consequently, the use of drug delivery systems decreases
side effects and increases therapeutic efficacy due to enhanced drug
retention in the intra-articular space. Additionally, the frequency
of intra-articular administration is reduced, as delivery systems
enable sustained drug release. This review summarizes various advanced
drug delivery systems, such as nano- and microcarriers, developed
for articular cartilage diseases.
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