Effectiveness of Small Interfering RNA Delivery via Arginine-Rich Polyethylenimine-Based Polyplex in Metastatic and Doxorubicin-Resistant Breast Cancer Cells.

Poor cellular uptake, rapid degradation in the presence of serum, and inefficient transfection are some of the major barriers in achieving therapeutic efficacy of naked small interfering RNAs (siRNAs). We investigated the efficacy of the polyplex formulated using our synthesized polymer, polyethylene glycol (PEG)-modified l-arginine oligo(-alkylaminosiloxane) that is grafted with poly(ethyleneimine) (PEI) for siRNA delivery. We hypothesized that the polyplex formulated using the polymer with a balanced composition of PEI for siRNA condensation and its protection, PEG for polyplex stability and to minimize the PEI-associated toxicity, and with arginine facilitating cellular uptake would overcome the aforementioned issues with siRNA delivery.

Big bottlenecks in cardiovascular tissue engineering.

Although tissue engineering using human-induced pluripotent stem cells is a promising approach for treatment of cardiovascular diseases, some limiting factors include the survival, electrical integration, maturity, scalability, and immune response of three-dimensional (3D) engineered tissues. Here we discuss these important roadblocks facing the tissue engineering field and suggest potential approaches to overcome these challenges.

Mechanical Properties, Cytocompatibility and Manufacturability of Chitosan:PEGDA Hybrid-Gel Scaffolds by Stereolithography.

Extracellular matrix mimetic hydrogels which hybridize synthetic and natural polymers offer molecularly-tailored, bioactive properties and tunable mechanical strength. In addition, 3D bioprinting by stereolithography allows fabrication of internal pores and defined macroscopic shapes. In this study, we formulated a hybrid biocompatible resin using natural and synthetic polymers (chitosan and polyethylene glycol diacrylate (PEGDA), respectively) by controlling molecular weight of chitosan, feed-ratios, and photo-initiator concentration.

Tissue plasminogen activator followed by antioxidant-loaded nanoparticle delivery promotes activation/mobilization of progenitor cells in infarcted rat brain.

Inherent neuronal and circulating progenitor cells play important roles in facilitating neuronal and functional recovery post stroke. However, this endogenous repair process is rather limited, primarily due to unfavorable conditions in the infarcted brain involving reactive oxygen species (ROS)-mediated oxidative stress and inflammation following ischemia/reperfusion injury. We hypothesized that during reperfusion, effective delivery of antioxidants to ischemic brain would create an environment without such oxidative stress and inflammation, thus promoting activation and mobilization of progenitor cells in the infarcted brain.

Arginine-rich polyplexes for gene delivery to neuronal cells.

Neuronal gene therapy potentially offers an effective therapeutic intervention to cure or slow the progression of neurological diseases. However, neuronal cells are difficult to transfect with nonviral vectors, and in vivo their transport across the blood-brain barrier (BBB) is inefficient. We synthesized a series of arginine-rich oligopeptides, grafted with polyethyleneimine (PEI) and modified with a short-chain polyethylene glycol (PEG).

Codelivery of DNA and siRNA via arginine-rich PEI-based polyplexes.

In this study, we formulated polyplexes with different compositions for codelivery of DNA and small-interfering RNA (siRNA). Since DNA and siRNA have distinctive and complementary morphological characteristics (DNA is long and winding and siRNA is short and rigid), we hypothesized that their codelivery using polyplex would enhance each other's transfection. To test this hypothesis, cationic polymer branched polyethylenimine (bPEI) as a standard transfecting agent and its derivative arginine-rich oligopeptide-grafted bPEI modified with polyethylene glycol (P(SiDAAr)5P3), synthesized in our laboratory, were used as carriers for transfection.

Superoxide dismutase-loaded biodegradable nanoparticles targeted with a follicle-stimulating hormone peptide protect Sertoli cells from oxidative stress.

Objective: To evaluate targeted superoxide dismutase (SOD)-loaded biodegradable nanoparticles' (NPs) ability to protect Sertoli cells from hydrogen peroxide (H2O2)-induced oxidative stress.

Design: Cell culture controlled experimental study.

Setting: Research laboratory.

Advances in stroke therapy.

Stroke is a leading cause of death, long-term disability, and socioeconomic costs, highlighting the urgent need for more effective treatments. Intravenous administration of tissue plasminogen activator (t-PA) is the only FDA-approved therapy to re-establish cerebral blood flow. However, because of increased risk of hemorrhage beyond 3 h post stroke, few stroke patients (1-2%) benefit from t-PA; t-PA, which has neurotoxic effects, can also aggravate the extent of reperfusion injury by increasing blood-brain barrier permeability.

Folate mediated l-arginine modified oligo (alkylaminosiloxane) graft poly (ethyleneimine) for tumor targeted gene delivery.

Folate receptor mediated gene targeting provides several advantages such as delivery of high concentration of gene at specific tumor sites including brain, lung, ovary, uterus and kidney where folate receptors are over expressed. In the present study for both systemic stability and tumor targeting ability, poly (ethylene glycol)-folic acid (PEG-FA) conjugate was coupled with an arginine modified oligo (alkylaminosiloxane) graft poly (ethyleneimine) having enhanced transfection efficiency compared to poly (ethyleneimine). The resultant polymer P(SiDAAr)5FP2 complexed pDNA effectively and showed protection against nuclease degradation.

Enhanced in-vitro transfection and biocompatibility of L-arginine modified oligo (-alkylaminosiloxanes)-graft-polyethylenimine.

Branched poly ethylene imine (PEI) has been considered as the most efficient non-viral gene transfection agent. However, its clinical application is confined due to cytotoxicity. In the present study, we tried to enhance transfection efficiency and reduce toxicity of PEI by conjugating it with arginine modified oligo(-alkylaminosiloxane) [P(SiDAAr)n].

Folate mediated in vitro targeting of depolymerised trimethylated chitosan having arginine functionality.

Delivery vectors having targeting ligands provide an impending impact on cancer gene therapy. Our work focuses on folate mediated targeting induced by conjugating poly(ethylene glycol)-folate (PEG-FA) with arginine modified chitosan polymer having low molecular weight of 15 kDa and high degree of quaternization (ATFP15H). The ATFP15H derivative on condensation with plasmid DNA formed nanoparticles with core shell nanostructure.

Folate mediated histidine derivative of quaternised chitosan as a gene delivery vector.

Folate targeted gene delivery vectors showed enhanced accumulation in folate receptor expressing tumor model. In the present work, the water solubility and transfection efficiency of chitosans were improved by modifying the depolymerised trimethylated chitosans with histidine moiety. Folate mediated targeting was induced by conjugating poly(ethylene glycol)-folate (PEG-FA) on histidine modified chitosan polymer having low molecular weight of 15 kDa and high degree of quaternisation (HTFP15-H).

Studies on the condensation of depolymerized chitosans with DNA for preparing chitosan-DNA nanoparticles for gene delivery applications.

High molecular weight chitosan (CS) was depolymerized by oxidative degradation with NaNO(2) at room temperature to get 11 samples of CS derivatives of varying molecular weights with a view to assessing their effective molecular weight range for gene delivery applications. Viscosity studies indicated that the molecular weight of the depolymerized CS was proportional to the CS/NaNO(2) ratio. The condensation behavior of DNA/CS complexes at various charge ratios was studied using UV spectroscopy, FTIR, CD, SEM, and AFM.