They have gained remarkable interest during the past decades and some of them have undergone clinical tests[ 2337 ]. They are intrinsically biocompatible, biodegradable and non-immunogenic. The natural surface can protect encapsulated cargos from inactivation with a remarkably prolonged and controllable lifespan in comparison to the synthetic carriers. These make them a valuable systemic drug release platform[ 38 ].
The polyplexes have formed spontaneously by mixing solutions of FATP and Nanogels because of ionic interactions between protonated polyethylenimine PEI chains in Nanogel network with polyphosphate groups of the drug.
This structure has provided a sustained release of the drug, as well as an efficient protection of FATP against enzymatic degradation.
The drug-Nanogel formulation compared to the drug has demonstrated a significantly enhanced cytotoxicity in cultured cancer cells.
Moreover, transcellular transport of the folate-Nanogel polyplexes was found to be 4 times more effective compared to the drug alone using Caco-2 cell monolayers as an in vitro intestinal model.
The data demonstrate that this carrier-based approach to delivery of cytotoxic drugs may enhance tumor specificity and significantly reduce side effects related to systemic toxicity usually observed during cancer chemotherapy.
In particular, polymeric carriers on the basis of polyethylenimine PEI have demonstrated strong potential for therapeutic gene delivery and transfection [ 3 — 5 ]. However, these polycationic drug carriers are far from ideal, and further developments need to reduce their toxicity, optimize circulation parameters and polyplex size [ 6 — 8 ].
Lately, a nanosized carrier based on a crosslinked network of branched PEI and poly ethylene glycol PEG molecules was synthesized and characterized [ 910 ].
This polymeric network has been called Nanogel and demonstrated an excellent swelling capacity and low buoyant density in aqueous media that made it a promising system for systemic drug delivery.
Because of polymer chain flexibility, the Nanogel network has markedly collapsed as a result of oligonucleotide binding, so that the volume of polyplex decreased by an order of magnitude comparing to the volume of initial Nanogel.
This volume has also depended on the oligonucleotide loading and environmental factors such as pH and salt concentration. The hydrophilic polymer envelope prevents the interaction between the drug-containing core and the blood components and allows for steric stabilization.
Alike, many negatively charged hydrophobic compounds were capable to form stable water-soluble complexes with Nanogel [ 11 ]. Physicochemical properties of Nanogel and biological activity of oligonucleotide-Nanogel formulations have been recently reviewed [ 12 ].
Obviously, more systematic studies are needed to fully understand drug delivery capabilities of Nanogel, as well as an application of this carrier to systemic cancer chemotherapy. Cancer chemotherapy is heavily relied on application of cytotoxic antimetabolites such as nucleoside analogs [ 1314 ].
Tissue selectivity of many nucleoside analogs is determined primarily by the activity of corresponding kinases, for example, the lymphoselectivity of fludarabine is explained by the uniquely high deoxycytidine kinase activity in cells of lymphoid origin [ 17 ]. As a result high doses of nucleoside analogs need to be used resulting in systemic toxicity and other adverse effects.
Furthermore, the non-specific tissue biodistribution of cytotoxic drugs significantly increases their systemic toxicity. Additionally, the development of various mechanisms of drug resistance has been demonstrated for different nucleoside analogs [ 1819 ].
The nucleoside analog-using chemotherapy could be enhanced through administration of nucleoside analogs encapsulated in drug delivery system, such as liposomes, to increase cellular accumulation and cancer-specific targeting of the drugs [ 2021 ].
Advanced drug carriers should have the following major properties: The swollen Nanogel particles contain protonated amino groups that are dispersed all over the volume of cross-linked polymer network and easily accessible to form complexes with negatively charged polyanions Figure 1.
The aim of this study was to evaluate properties of Nanogels formulated with phosphorylated nucleoside analogs and application of these formulations to cancer chemotherapy.Dipeptide Nanogels for Anticancer Drug Delivery JIBAN J.
PANDA and *VIRANDER S. CHAUHAN International Centre for Genetic Engineering and Biotechnology. Abstract.
Noninvasive and Local Delivery of Adenoviral-Mediated Herpes Simplex Virus Thymidine Kinase to Treat Glioma Through Focused Ultrasound-Induced. Dipeptide Nanogels for Anticancer Drug Delivery JIBAN J. PANDA and *VIRANDER S. CHAUHAN International Centre for Genetic Engineering and Biotechnology. Zr 2 N 2 O Coating-Improved Corrosion Resistance for the Anodic Dissolution Induced by Cathodic Transient Potential.
Natural cells have been explored as drug carriers for a long period. They have received growing interest as a promising drug delivery system (DDS) until recently along with the development of biology and medical science.
Floxuridine-containing nucleic acid nanogels for anticancer drug delivery. Yuan Ma, a Hongxia Liu, b Quanbing Mou, a Deyue Yan, a Xinyuan Zhu a and Chuan Zhang * a Author affiliations * Corresponding authors. Nanogels are superior drug delivery system than others because 1.
The particle size and surface properties can be manipulated to anticancer drugs more effectively. CHP is composed of pullulan backbone and cholesterol branches. The CHP molecules self. Sep 20, · Hydrophilic nanosized particles consisting of the cross-linked cationic polymer network (Nanogels) are suggested as a drug delivery system for nucleoside analog 5’-triphosphates, an active form of cytotoxic anticancer drugs.
Noninvasive and Local Delivery of Adenoviral-Mediated Herpes Simplex Virus Thymidine Kinase to Treat Glioma Through Focused Ultrasound-Induced.