Study of the influence of ascorbyl palmitate and amiodarone in the stability of unilamellar liposomes

Abstract

Amiodarone (AMI) is a low water-solubility drug, which is very useful in the treatment of severe cardiac disease. Its adverse effects are associated with toxicity in different tissues. Several antioxidants have been shown to reduce, and prevent AMI toxicity. The aim of this work was to develop and characterize Dimyristoylphosphatidylcholine (DMPC) liposomal carriers doped with ascorbyl palmitate (Asc16) as antioxidant, in order to either minimize or avoid the adverse effects produced by AMI. The employment of liposomes would avoid the use of cosolvents in AMI formulations, and Asc16 could minimize the adverse effects of AMI. To evaluate the partition and integration of AMI and Asc16 in lipid membranes, penetration studies into DMPC monolayers were carried out. The disturbance of the liposomes membranes was studied by generalized polarization (GP). The stability of liposomes was evaluated experimentally and by means of the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. The size particle and zeta potential (ζ) values of the liposomes were used for application in calculations for attractive and repulsive forces in DLVO theory. In experimental conditions all of these vesicles showed stability at time 0, but only DMPC + Asc16 10% + AMI 10% liposomes kept their size stable and ζ during 28 days. These results are encouraging and suggest that such systems could be suitable for AMI delivery formulations.

Alkyl esters of l-ascorbic acid: Stability, surface behaviour and interaction with phospholipid monolayers

“…4A) [15]. The presence of an initial peak was also observed for the adsorption of amiodarone (cationic amphiphilic drug) to the air/water interface [42], suggesting a general behaviour for the adsorption of charged amphiphiles. Fig.…”

“…The presence of the acyl chain, besides improving its solubility in alcohol and non-polar solvents, provides the capacity to self-organize into micelles and coagel when suspended in water [3]. ASC n aggregates have been proposed as drug delivery nanostructures capable of providing antioxidant protection to sensitive drugs [2] and as valuable components of phosphatidylcholine (PC)-based liposomes for drug delivery [4].…”

Solid lipid nanoparticles for the delivery of anti-microbial oligonucleotides

“…As shown in Table 2, the particles presented a size around 100 nm and negative zeta potential. Incorporation of ascorbyl palmitate (A-TPAP) made the particles slightly bigger but with a lower negative zeta potential, an effect that has been previously reported for other lipid nanocarriers containing ascorbyl palmitate [32,33]. Coating with THA did not affected size, but caused inversion of zeta potential from negative to positive, due to effective interaction between the cationic compound and SLN surface.…”

The amphiphilic alkyl ester derivatives of l -ascorbic acid induce reorganization of phospholipid vesicles

“…In addition, another advantage of the amphipathic character of ASCn is their ability to form aggregates in aqueous solutions or to be integrated into lipid vesicles, which offer a suitable environment for the storage and transport of hydrophobic substances susceptible to oxidation [6]. In fact, some ASCn such as ascorbyl laurate (ASC12), ascorbyl myristate (ASC14) and ascorbyl palmitate, (ASC16) self-organize as coagels at relative high ASCn/water ratio [1].…”

“…One approach to tackle this issue is the generation of amphiphilic derivatives of Vitamin C like alkanoyl-6-Oascorbic acid esters (ASCn), which are known to maintain the antioxidant character of ascorbic acid and to partition into non-polar milieus [2,3]. These modifications make to this drug family a very attractive tool for being used in pharmacological preparations since there are experimental evidences indicating a strong connection between oxidative damage, cancer, and aging [4,5].In addition, another advantage of the amphipathic character of ASCn is their ability to form aggregates in aqueous solutions or to be integrated into lipid vesicles, which offer a suitable environment for the storage and transport of hydrophobic substances susceptible to oxidation [6]. In fact, some ASCn such as ascorbyl laurate (ASC12), ascorbyl myristate (ASC14) and ascorbyl palmitate, (ASC16) self-organize as coagels at relative high ASCn/water ratio [1].…”