Abstract:
A thermogelling, aliphatically modified polymer for use in drug delivery is described. Illustrative embodiments include poly(lactic-co-ε-caprolactone)-poly(ethylene glycol)-poly(lactic-co-ε-caprolactone) hexanoate and poly(lactic-co-ε-caprolactone)-poly(ethylene glycol)-poly(lactic-co-ε-caprolactone) laurate. Another illustrative embodiment includes a composition having a thermogelling amount of an aliphatically modified poly(lactic-co-ε-caprolactone)-poly(ethylene glycol)-poly(lactic-co-ε-caprolactone) and an effective amount of a drug. The thermogelling polymers are made by bonding an aliphatic group to poly(lactic-co-ε-caprolactone)-poly(ethylene glycol)-poly(lactic-co-ε-caprolactone). A method of use includes injecting a warm-blooded individual with a thermogelling amount of the aliphatically modified polymer and a drug.
Abstract:
An arginine-grafted bioreducible poly(disulfide amine) (“ABP”) as a reagent for efficient and nontoxic gene delivery is described. ABP forms positively charged nano-particles of less than 200 nm with siRNA. ABP is biodegraded under reducing conditions, such as in the cytoplasm. ABP exhibits much higher transfection efficiency than polyethyleneimine in mammalian cells and exhibits no cytotoxicity. ABP is an effective delivery vehicle for gene silencing with siRNA and may be used for treating cancer.
Abstract:
Poly(disulfide amine)s, methods of making, and methods of use are described. Illustrative embodiments of the poly(disulfide amine)s include poly(CBA-DAE), poly(CBA-DAB), and poly(CBA-DAH). These compositions are made by Michael addition between N,N′-cystaminebisacrylamide and N-Boc-protected diamine monomers, followed by N-Boc deprotection. Complexes are formed by mixing the poly(disulfide amine)s with nucleic acid. Delivery of the nucleic acid into cells is carried out by contacting the cells with the nucleic acid/poly(disulfide amine) complexes.
Abstract:
A method for delaying onset of insulin dependent diabetes mellitus (IDDM) in an individual predisposed to developing the disease is disclosed. The method comprises administering a composition comprising an immunologically effective monoclonal antibody or fragment thereof against glutamic acid decarboxylase (GAD) coupled to a nonimmunogenic hydrophilic polymer that provides a hydration shell around the monoclonal antibody for inhibiting immune recognition thereof. Poly(ethylene glycol) is a preferred polymer. A method of reducing insulitis in an IDDM patient and a composition therefor are also described.
Abstract:
A composition for delivery of a selected nucleic acid into a targeted host cell comprises a complex of a hydrophobized, positively charged, biocompatible polymer; a lipoprotein; and a selected nucleic acid. Hydrophobic and electrostatic interactions between the components provide for the formation of the condensed DNA-containing complex. Preferred embodiments of the complex have a slightly positive surface charge and an average diameter of about 200 nm. Plasmids and oligonucleotides can be efficiently delivered with such compositions. A method of delivering a selected nucleic acid to a host cell is also disclosed.
Abstract:
Disclosed is an on-line advertisement method using an advertisement website. An on-line advertisement method according to an embodiment of the present invention provides an advertisement available to a user terminal at a current position of a user terminal which accesses an advertisement website.
Abstract:
A biologic ventricular assist device that also has the capability to capture, grow, and administer stem cells to regenerate and restore damaged myocardium in the heart. The device works in conjunction with a traditional ventricular assist device and possesses an additional external path or tube that is in-line with the path of the ventricular assist device. The external path allows for the administration of stem cells, genes, genetically modified cells or other therapeutic biologic or pharmacologic agents, as well as leading to a stem cell collecting accessory (14) that captures circulating stem cells. The stem cell collecting accessory is also associated with a chamber (39) for culturing the captured stem cells. The cultured stem cells can be delivered back to the heart by an electro-mechanical or ultrasound/echocardiographic delivery system that runs through the external path back into the ventricular assist device and allows for the delivery of the stem cells, or other therapeutic biologic or pharmacologic agents, directly into the internal chambers of the heart. Administering the stem cells, genes, genetically modified cells or other therapeutic biologic or pharmacologic agents, either alone or in combination, to the heart allows the myocardium to regenerate and repair itself even while the heart is attached to the ventricular assist device, ultimately allowing the heart to regenerate, recover and allow the VAD to be removed.
Abstract:
An arginine-grafted bioreducible poly(disulfide amine) (“ABP”) as a reagent for efficient and nontoxic gene delivery is described. ABP forms positively charged nano-particles of less than 200 nm with siRNA. ABP is biodegraded under reducing conditions, such as in the cytoplasm. ABP exhibits much higher transfection efficiency than polyethyleneimine in mammalian cells and exhibits no cytotoxicity. ABP is an effective delivery vehicle for gene silencing with siRNA and may be used for treating cancer.
Abstract:
A carrier for delivering small interfering RNA (siRNA) into cells includes a cholesterol residue covalently bonded to oligoarginine. Mixing the siRNA with the carrier produces a complex-containing composition. Contacting a cell with the complex-containing composition results in delivery of the siRNA into the cell. Delivery of an siRNA targeted to vascular endothelial growth factor is a treatment for cancer. Methods of making the carrier and complex are also disclosed.
Abstract:
Plasmids useful for treating ischemic disease, such as ischemic heart disease, are described. The plasmids express vascular endothelial growth factor (VEGF) under the control of a promoter (RTP801) that is up-regulated under hypoxic conditions. Pharmaceutical compositions for treating ischemic disease include mixtures of the hypoxia-regulated VEGF plasmids and pharmaceutically acceptable carriers. Methods for treating ischemic disease include administering such pharmaceutical compositions to a person in need of such treatment.