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Micelle-forming block copolymer–drug conjugates, Adriamycin-conjugated polyethylene glycol–poly(aspartic acid) block copolymers (PEG-P(Asp(ADR))), were synthesized in eight compositions with varying chain lengths of the segments constituting the block co-polymer. The antitumor activity of...
The delivery of hydrophilic drugs, peptides, and proteins to the brain is restricted by tight junctions between the endothelial cells of the cerebral capillaries which contribute to the blood–brain barrier (BBB). Injection of liposomes as drug delivery vehicles is re-ported to enhance the...
Previous studies have demonstrated that the antitumor effect of melphalan can be increased by the administration of the vasodilator hydralazine. This potentiation is due to the induction of hypoxia, which is known to potentiate melphalan cytotoxicity. In this study we investigated whether the...
The pharmacologic efficacy of antisense oligonucleotide- or peptide-based therapeutics in intact organisms is limited by the poor transport of these highly charged molecules across cellular membranes. Since recent studies have shown that avidin, a cationic protein, is taken up by cells via...
Drug–antibody conjugates are undergoing close scrutiny as new antitumor agents because they confer increased drug specificity, producing higher accumulation in the tumor and less systemic toxicity than free drug. Consequently this has led to the use of drugs more toxic than those that can...
The enhancing properties of clofibric acid amides on the transdermal delivery of indomethacin and levonorgestrel were studied in vitro using full-thickness hairless mouse skin. The enhancers possessed alkyl side chains varying from 2 (1) to 16 (7) carbons. Indomethacin was applied in propylene...
We have previously demonstrated that 1-β-D-arabinofuranosylcytosine (ara-C) entrapped in long-circulating formulations of liposomes (Stealth, or sterically stabilized) was an effective sustained release system following intravenous (iv) or intraperitoneal (ip) administration ( Cancer Res . 52,...
Onconase, a protein isolated from fertilized Rana pipiens eggs, has antineoplastic properties both in vitro (Z. Darzynkiewicz, S. P. Carter, S. M. Mikulski, W. Ardelt, and K. Shogen, 1988, Cell Tissue Kinet . 21, 169–182) and in vivo (S. M. Mikulski, W. Ardelt, K. Shogen, E. H. Bernstein, and...
Phospholipid vesicles containing the ionophore A23187 in the bilayer (VesCan) are the only liposomes produced for clinical imaging purposes. We undertook preliminary experiments with In-loaded VesCan (indium-111-V-liposome) using normal rabbits and nude mice bearing human gastric (MKN45) and...
Preformulation studies were conducted to determine the feasibility of a transdermal dosage form of prazosin hydrochloride (PZHC1). A target PZHC1 skin flux of 6.3 μg/cm 2 /h was set to attain a steady-state plasma concentration of 10 ng/ml (from a 20-cm 2 skin area). The octanol/water partition...
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