Interaction of dipyridamole with lipids in mixed Langmuir monolayers

Abstract

Dipyridamole (DIP), a well known coronary vasodilator and coactivator of anti-tumor activity of a number of drugs, forms stable Langmuir monolayers with the zwitterionic lipid dipalmitoylphosphatidylcholine (DPPC) and the negatively charged dipalmitoylphosphatidylglycerol (DPPG) at an air/aqueous solution interface. The drug binds to the lipid molecules and change their packing density in the monolayer in the process of compression, the effect depending on the drug location in the monolayer, protonation of the drug and also on the charge state of the lipid. The incorporation of dipyridamole (DIP) into neutral DPPC monolayers causes them to be more expanded at low DIP concentrations but more condensed at high concentrations, resembling the effect of cholesterol. Maximum expansion occurs for a DIP concentration of 2 mol%. For slightly charged DPPG monolayers spread on ultra pure water, the monolayers become increasingly more expanded with increasing DIP concentrations. For the negatively charged DPPG monolayers spread on buffer solutions, the incorporation of DIP has similar effects to that observed for DPPC monolayers. This is probably due to the interaction between the charged DPPG molecules and the protonated DIP molecules. Also, introduction of protonated DIP brings an increase in surface potential of DPPG monolayers because the negative contribution from the double layer is decreased. The results indicated that DIP molecules are located deeper in the hydrophobic region of DPPC monolayers, whereas in DPPG ones they appear to be located very close to the polar head region. Due to the electrostatic interaction of protonated DIP with the charges on the polar heads of lipids it is inclined with respect to the plane of the monolayer.

Interactions of bioactive molecules & nanomaterials with Langmuir monolayers as cell membrane models

“…Grazing incidence X-ray diffraction and quantum mechanical studies [240]. PM-IRRAS experiments confirmed the earlier observation [241] that the drug interacts peripherally with the zwitterionic lipid headgroup, but does not intercalate deeply between lipid molecules [239]. Apolar interactions were found to be important only for DIP hydrophobic derivatives [242].…”

“…Typical examples include: antimicrobials [117,, anti-tumorals [116,, antiinflammatory [77,[214][215][216][217], anesthesics [218][219][220][221][222][223][224][225][226][227], anti-psychotics [228][229][230][231][232][233][234][235][236][237], cardiac [238][239][240][241][242][243][244][245] and antihistaminic [246] drugs. To address this issue, Langmuir monolayers have been used involving AmB alone as well as mixed with membrane sterols.…”

Effects of dipyridamole on Plasmodium falciparum -infected erythrocytes

“…1). After permeating lipid membranes, the polarizable heteromatic cycle of DP tends to be situated at the border of the polar heads of lipids and hydrophobic tails, while aliphatic side groups are introduced into the hydrophobic phase of the lipids (Borissevitch et al 1995(Borissevitch et al , 1996. The DP molecule is associated with lipids via electrostatic interaction and hydrogen bonding (Caetano et al 2001).…”

Caracterização das monocamadas mistas (DPPC+BCD) de Langmuir: efeito da estrutura e concentração do BCD e da força iônica na subfase

“…A isoterma (ΔV-Α) do DPPC, mostrada na figura 5.22, apresenta potencial zero para grandes distâncias entre as moléculas (grandes valores de área por molécula), aumenta abruptamente a partir de (120±5) Å 2 e atinge o valor máximo de potencial que fica compreendido no intervalo [500;600] mV, concordando com (Borissevitch et al 1996). Este rápido aumento tem sido atribuído, para monocamadas de fosfolipídios e de outros compostos alifáticos, à diminuição da constante dielétrica efetiva na interface monocamada-água que ocorre quando uma determinada densidade de empacotamento é atingida (Borissevitch et al 1996).…”

“…Este rápido aumento tem sido atribuído, para monocamadas de fosfolipídios e de outros compostos alifáticos, à diminuição da constante dielétrica efetiva na interface monocamada-água que ocorre quando uma determinada densidade de empacotamento é atingida (Borissevitch et al 1996). Como discutido na seção 5.…”