Objective: The objective of this investigation is to develop mathematical equation to understand the impact of variables and establish statistical control over transdermal iontophoretic delivery of tacrine hydrochloride. In addition, possibility of using conductivity measurements as a tool of predicting ionic mobility of the participating ions for the application of iontophoretic delivery was explored.
Methods: Central composite design was applied to study effect of independent variables like current strength, buffer molarity, and drug concentration on iontophoretic tacrine permeation flux. Molar conductivity was determined to evaluate electro-migration of tacrine ions with application of Kohlrausch's law.
Results: The developed mathematic equation not only reveals drug concentration as the most significant variable regulating tacrine permeation, followed by current strength and buffer molarity, but also is capable to optimize tacrine permeation with respective combination of independent variables to achieve desired therapeutic plasma concentration of tacrine in treatment of Alzheimer's disease. Moreover, relative higher mobility of sodium and chloride ions was observed as compared to estimated tacrine ion mobility.
Conclusions: This investigation utilizes the design of experiment approach and extends the primary understanding of imapct of electronic and formulation variables on the tacrine permeation for the formulation development of iontophoretic tacrine delivery.
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http://dx.doi.org/10.1080/03639045.2016.1181646 | DOI Listing |
Int J Mol Sci
June 2022
OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal.
Nanoparticulate systems have been widely investigated as delivery vectors for efficient drug delivery in different diseases. Nanostructured lipid carriers (NLC) are composed of both solid and liquid lipids (glyceryl dibehenate and diethylene glycol monoethyl ether) and have demonstrated enhanced biological compatibility and increased drug loading capability. Furthermore, the use of peptides, in particular cell-penetrating peptides, to functionalize nanoparticles and enhance cell membrane permeation was explored in this paper.
View Article and Find Full Text PDFMolecules
August 2021
Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai 90112, Songkhla, Thailand.
A quinoxaline scaffold exhibits various bioactivities in pharmacotherapeutic interests. In this research, twelve quinoxaline derivatives were synthesized and evaluated as new acetylcholinesterase inhibitors. We found all compounds showed potent inhibitory activity against acetylcholinesterase (AChE) with IC values of 0.
View Article and Find Full Text PDFACS Chem Neurosci
May 2021
Department of Pharmacy and Biotechnology, University of Bologna, Via Belmeloro 6/Selmi 3, 40126 Bologna, Italy.
Since 2002, no clinical candidate against Alzheimer's disease has reached the market; hence, an effective therapy is urgently needed. We followed the so-called "multitarget directed ligand" approach and designed 36 novel tacrine-phenothiazine heterodimers which were evaluated for their anticholinesterase properties. The assessment of the structure-activity relationships of such derivatives highlighted compound as a potent and selective acetylcholinesterase inhibitor with IC = 8 nM and as a potent butyrylcholinesterase inhibitor with IC = 15 nM.
View Article and Find Full Text PDFBiomolecules
December 2020
Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic.
Alzheimer's disease (AD) is a complex disorder with unknown etiology. Currently, only symptomatic therapy of AD is available, comprising cholinesterase inhibitors and -methyl-d-aspartate (NMDA) receptor antagonists. Drugs targeting only one pathological condition have generated only limited efficacy.
View Article and Find Full Text PDFEur J Med Chem
February 2021
Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing, 211189, China; Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing, 211189, China. Electronic address:
Current drugs available in clinic for Alzheimer's disease (AD) treatment can only alleviate disease symptoms without clearly curing or delaying the process of AD. And some AD drugs failed in Phase III clinical trials are only focused on targeting amyloid-β (Aβ). Therefore, an alternative strategy in AD drug design is meaningful to be involved in the multiple pathogenic factors which can affect each other at multiple levels.
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