Designing siRNA/chitosan-methacrylate complex nanolipogel for prolonged gene silencing effects.

Despite immense revolutionary therapeutics potential, sustaining release of active small interfering RNA (siRNA) remains an arduous challenge. The development of nanoparticles with siRNA sustained release capabilities provides an avenue to enhance the therapeutic efficacy of gene-based therapy. Herein, we present a new system based on the encapsulation of siRNA/chitosan-methacrylate (CMA) complexes into liposomes to form UV crosslinkable Nanolipogels (NLGs) with sustained siRNA-release properties in vitro.

Liposomal Nanotherapy for Treatment of Atherosclerosis.

Atherosclerosis is a chronic disease that can lead to life-threatening events such as myocardial infarction and stroke, is characterized by the build-up of lipids and immune cells within the arterial wall. It is understood that inflammation is a hallmark of atherosclerosis and can be a target for therapy. In support of this concept, an injectable nanoliposomal formulation encapsulating fluocinolone acetonide (FA), a corticosteroid, is developed that allows for drug delivery to atherosclerotic plaques while reducing the systemic exposure to off-target tissues.

Targeting efficiency of nanoliposomes on atherosclerotic foam cells: polyethylene glycol-to-ligand ratio effects.

Background: Nanoparticles that actively target tissues, with ligands attached at the extremity of polyethylene glycol (PEG) spacer, are a promising strategy to enhance target cell specificity and internalization. However, the interplay between the targeting ligands and the adjacent ligand-free PEG remains poorly understood.

Research Design And Methods: Experimentally, liposomes containing active folate ligands were firstly formulated and the optimum amount of ligand that yields the highest foam cell uptake was determined.

Nanolipogels as a cell-mimicking platform for controlled release of biomacromolecules.

We present studies of protein (insulin) efflux rates from nano-sized core-shell systems with a gelled core and a lipid bilayer (nanolipogels). The efflux control mechanism is the manipulation of mesh size, and we show that diffusion control crosslinking is the dominant mechanism for efflux control. The concept is inspired by the macromolecular crowding effect in human cells, which may be considered as a physical network of undefined mesh size.

Recent Advances in Chitosan-Based Carriers for Gene Delivery.

Approximately 4000 diseases are associated with malfunctioning genes in a particular cell type. Gene-based therapy provides a platform to modify the disease-causing genes expression at the cellular level to treat pathological conditions. However, gene delivery is challenging as these therapeutic genes need to overcome several physiological and intracellular barriers in order, to reach the target cells.

Design and in vitro release study of siRNA loaded Layer by Layer nanoparticles with sustained gene silencing effect.

Objectives: Clinical translation of siRNA therapeutics has been severely limited due to the lack of stable and sustained siRNA delivery systems. Furthermore, when nanocarrier systems with siRNA are administered systemically to treat diseases, insufficient doses reach the target tissue. Here we report the successful development of a new nanocarrier system for the management of fibrosis.

Targeted therapy for the post-operative conjunctiva: SPARC silencing reduces collagen deposition.

Background: To develop targeted antifibrotic therapy for glaucoma filtration surgery; this study determines the effectiveness of small interfering RNA (siRNA) to reduce in vivo secreted protein acidic and rich in cysteine (SPARC) expression using the mouse model of conjunctival scarring.

Methods: Experimental surgery was performed as described for the mouse model of conjunctival scarring. Scrambled (siScram) or Sparc (siSparc) siRNAs, loaded on layer-by-layer (LbL) nanoparticles, were injected into the conjunctiva immediately after surgery.

Controlled-release nanotherapeutics: State of translation.

This is a review of nanotherapeutic systems, specifically those that exhibit controlled release of the encapsulated bioactive compound. The survey includes the delivery of a range of bioactive compounds, from lipophilic small molecules to hydrophilic proteins and siRNA molecules. The research into enabling sustained delivery of these compounds from nanocarriers has been prolific, but clinical success has been harder to achieve.

Layer-by-layer nanoparticles as an efficient siRNA delivery vehicle for SPARC silencing.

Efficient and safe delivery systems for siRNA therapeutics remain a challenge. Elevated secreted protein, acidic, and rich in cysteine (SPARC) protein expression is associated with tissue scarring and fibrosis. Here we investigate the feasibility of encapsulating SPARC-siRNA in the bilayers of layer-by-layer (LbL) nanoparticles (NPs) with poly(L-arginine) (ARG) and dextran (DXS) as polyelectrolytes.

Multimodal tumor imaging by iron oxides and quantum dots formulated in poly (lactic acid)-D-alpha-tocopheryl polyethylene glycol 1000 succinate nanoparticles.

This work developed a multimodal imaging system by co-encapsulating superparamagnetic iron oxides (IOs) and quantum dots (QDs) in the nanoparticles of poly (lactic acid) - d-α-tocopheryl polyethylene glycol 1000 succinate (PLA-TPGS) for concurrent imaging of the magnetic resonance imaging (MRI) and the fluorescence imaging to combine their advantages and to overcome their disadvantages as well as to promote a sustained and controlled imaging with passive targeting effects to the diseased cells. The QDs and IOs-loaded PLA-TPGS NPs were prepared by a modified nanoprecipitation method, which were then characterized for their size and size distribution, zeta potential and the imaging agent encapsulation efficiency. The transmission electron microscopy (TEM) images showed direct evidence for the well-dispersed distribution of the QDs and IOs within the PLA-TPGS NPs.