Novel dendritic derivatives of unsaturated fatty acids as promising transdermal permeation enhancers for tenofovir

Abstract

This study was aimed at exploring the potential of unsaturated fatty acids (UFAs) [palmitoleic (PA), linoleic (LA), linolenic (LLA) and arachidonic acid (AA)], and their newly synthesized dendritic esters [PA1E, LA1E, LLA1E and AA1E] having basic tertiary nitrogen as the branching element as transdermal permeation enhancers for the delivery of tenofovir. The structures of the derivatives were confirmed by FTIR, NMR ( 1 H and 13 C) and HRMS. The in vitro cytotoxicity study revealed their biocompatibility. Amongst the UFAs, only PA and LLA exhibited transdermal enhancer potential [enhancement ratio (ER) of 1.35 and 2.9respectively]. All synthesized derivatives at 1% w/w were found to be more effective enhancers as compared to their parent UFAs, with LLA1E being identified as the most superior (ER = 5.31). Further, the concentration effect study revealed that at 2% w/w LLA1E had a greater ER (6.11) as compared to its parent (ER = 3.85). The permeability data correlated with the observations made in the histomorphological and transepithelial electrical resistance (TEER) evaluations. There was no significant loss in the integrity of the epidermis, transcellular and intercellular route of transport across the epidermis, with drug and enhancer treatment having no permanent damage on the epidermis. The novel dendritic ester derivatives of the UFAs therefore can be considered as effective transdermal permeation enhancers.

Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study

“…NEs were prepared by an ultra-sonication method ( 22 ) using mixtures of linolenic acid ester (LLA1E) ( 20 ) as the oily phase, Solutol HS 15 ® and PEG 400 as the surfactant/co-surfactant mixture (S mix ). The oily phase (LLA1E) and the S mix were mixed, the required quantity of milli-Q water was added and sonicated [probe Omni Sonic Ruptor 400 Ultrasonic Homogenizer (OMNI International, Kennesaw, GA, USA)] at 30% amplitude for 10 min (20°C) to form the blank NE.…”

“…Only a few local toxicity studies on transdermal skin effect ( 17 ) vaginal routes ( 18 , 19 ) and invitro studies ( 16 ) were reported. Tenofovir nanoparticles (NTDF) with novel dendritic properties have been developed by our team, invitro toxicity evaluation of the lipid component showed promising results ( 20 ). NTDF has potential to revolutionize the treatment of HIV infection through its effective penetration, reduction in administration frequency and effectiveness in attacking latent HIV virus in restricted areas in the body.…”

Non-ionic self-assembling amphiphilic polyester dendrimers as new drug delivery excipients

“…53,54 The test material displaying percentage cell viability >70% can be considered as biologically safe and nontoxic to mammalian cells. 55 The biosafety of all ADs can be attributed to selection of non-toxic and biodegradable building blocks used for their synthesis.…”

Transforming linoleic acid into a nanoemulsion for enhanced activity against methicillin susceptible and resistant Staphylococcus aureus

“…The optical density of each well was measured on a microplate spectrophotometer (Mindray MR-96A) at a wavelength of 540 nm. 39 The percentage cell viability was calculated as follows:…”