Search results for "Prodrug"

ChemInform Abstract: Synthesis and in vitro Studies on a Potential Dopamine Prodrug.

2009

Dopamine delivery to the central nervous system (CNS) undergoes the permeability limitations of blood-brain barrier (BBB) which is a selective interface that excludes most water-soluble molecules from entering the brain. Neutral amino acids permeate the BBB by specific transport systems. Condensation of dopamine with neutral amino acids could afford potential prodrugs able to interact with the BBB endogenous transporters and easily enter the brain. The synthesis and characterization of the dopamine derivative 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (7) is described. The chemical and enzymatic stability of 7 was evaluated. The molecular weight (300 Da) and Log Papp (…

Polyaminoacid–doxorubicin prodrug micelles as highly selective therapeutics for targeted cancer therapy

2016

An amphiphilic copolymer carrying high-dose doxorubicin (21% on a weight basis), PHEA–EDA–P,C–Doxo, was prepared by coupling doxorubicin with a biocompatible polyaminoacid through a pH-sensitive spacer. Additional derivatization with 4-pentynoic acid endows it with self-assembling properties by means of π–π stacking. These micelles can be triggered to promptly release drug in lysosomes (∼40% in 12 h) through pH-dependent micelle hydrolysis after uptake. In vitro tests on co-cultures of cancer (MDA-MB 231) and normal (HB-2) breast cells proved that the conjugate was selectively internalized into the former rather than normal cells, exploiting the caveolae-dependent endocytosis pathway, expla…

Multistage rocket: integrational design of a prodrug-based siRNA delivery system with sequential release for enhanced antitumor efficacy.

2018

An integrated peptide-camptothecin prodrug (RSC) system was designed as a nano-sized multistage rocket for the efficient complexation and controlled sequential release of siRNA and anticancer drug under tumor-relevant reductive and esterase-enriched conditions, which facilitated the avoidance of negative interactions and maximized the synergistic effect.

o-Ethoxybenzamid-Mannichbasen als potentielle Prodrugs. o-Ethoxybenzamide Mannich Bases as Potential Prodrugs

1986

Studies on a new potential dopaminergic agent: in vitro BBB permeability, in vivo behavioural effects and molecular docking evaluation.

2015

2-Amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (DA-PHEN) has been previously synthesized to obtain a potential prodrug capable of release dopamine (DA) into CNS. However, DA-PHEN could act per se as a dopaminergic drug. In this study, the permeability transport (Pe), obtained by parallel artificial permeability assay (PAMPA), indicated a low passive transcellular transport (Pe = 0.32 ± 0.01 × 10(-6 )cm/s). Using the Caco-2 cell system, the Papp AP-BL in absorptive direction (3.36 ± 0.02 × 10(-5 )cm/s) was significantly higher than the Papp BL-AP in secretive direction (1.75 ± 0.07 × 10(-5 )cm/s), suggesting a polarized transport. The efflux ratio (Papp AP-BL/Papp BL-AP = 0…

Bisphosphonate prodrugs utilizing endogenous carriers

2016

Targeting of therapeutic agents to a specific site, as well as controlling the rate and time of release, has been intensively investigated and established over the last decades. These studies concerning drug delivery systems led to the formulation of several products that can improve the diffusion across the barriers after drug administration. For this purpose, the development of strategies of novel drug delivery systems for bisphosphonates had taken hold to improve both the bioavailability and safety. Firstly, they have been used for over a century in the branch of industry and later, in the 1960s, in medicine. Bisphosphonates are synthetic compound analogs to the naturally occurring pyrop…

Coupling of the antiviral agent zidovudine to polyaspartamide and in vitro drug release studies.

1998

A macromolecular prodrug of the known antiretroviral agent zidovudine and alpha, beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) was synthesized. A succinic spacer was present between the polymer and the drug, and 1,1'-carbonyldiimidazole was used as the coupling agent. In vitro drug release studies at pH 1.1, 5.5 and 7.4 indicated that limited amounts of intact drug were released from the conjugate. At pH 1.1 and 7.4 succinylzidovudine was released, and this was hydrolysed to give free zidovudine. In the presence of alpha-chymotrypsin, zidovudine was released preferentially in comparison with the succinyl derivative. The amounts of released zidovudine and succinylzidovudine were greater …

Dendrimers as Non-Viral Vectors in Gene-Directed Enzyme Prodrug Therapy.

2021

Gene-directed enzyme prodrug therapy (GDEPT) has been intensively studied as a promising new strategy of prodrug delivery, with its main advantages being represented by an enhanced efficacy and a reduced off-target toxicity of the active drug. In recent years, numerous therapeutic systems based on GDEPT strategy have entered clinical trials. In order to deliver the desired gene at a specific site of action, this therapeutic approach uses vectors divided in two major categories, viral vectors and non-viral vectors, with the latter being represented by chemical delivery agents. There is considerable interest in the development of non-viral vectors due to their decreased immunogenicity, higher…

Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Enalapril

2018

Literature data relevant to the decision to allow a waiver of in vivo bioequivalence testing for the marketing authorization of immediate-release, solid oral dosage forms containing enalapril maleate are reviewed. Enalapril, a prodrug, is hydrolyzed by carboxylesterases to the active angiotensin-converting enzyme inhibitor enalaprilat. Enalapril as the maleate salt is shown to be highly soluble, but only 60%-70% of an orally administered dose of enalapril is absorbed from the gastrointestinal tract into the enterocytes. Consequently, enalapril maleate is a Biopharmaceutics Classification System class III substance. Because in situ conversion of the maleate salt to the sodium salt is sometim…

Potential transbuccal delivery of l-DOPA methylester prodrug: stability in the environment of the oral cavity and ability to cross the mucosal tissue

2016

Levodopa (l-DOPA) is the most effective pharmacologic agent in Parkinson's disease and remains the "gold standard". Nevertheless, in long-term treatments, dyskinesias and motor complications can emerge. In this work, the combined use of l-DOPA methylester hydrochloride prodrug (LDME) with transbuccal drug delivery was supposed as a good alternative method to optimize the bioavailability of l-DOPA, to maintain constant plasma levels and to decrease the drug unwanted effects. The effects of environmental pH on buccal delivery of LDME were evaluated ex vivo. The increase of pH value from 5.8 to 6.2 implies an improvement of drug permeation. Since the pH increase causes the raising of hydrolyti…