Determining drug release rates of hydrophobic compounds from nanocarriers

Abstract

Obtaining meaningful drug release profiles for drug formulations is essential prior to in vivo testing and for ensuring consistent quality. The release kinetics of hydrophobic drugs from nanocarriers (NCs) are not well understood because the standard protocols for maintaining sink conditions and sampling are not valid owing to mass transfer and solubility limitations. In this work, a new in vitroassay protocol based on 'lipid sinks' and magnetic separation produces release conditions that mimic the concentrations of lipid membranes and lipoproteins in vivo, facilitates separation, and thus allows determination of intrinsic release rates of drugs from NCs. The assay protocol is validated by (i) determining the magnetic separation efficiency, (ii) demonstrating that sink condition requirements are met, and (iii) accounting for drug by completing a mass balance. NCs of itraconazole and cyclosporine A (CsA) were prepared and the drug release profiles were determined. This release protocol has been used to compare the drug release from a polymer stabilized NC of CsA to a solid drug NP of CsA alone. These data have led to the finding that stabilizing block copolymer layers have a retarding effect on drug release from NCs, reducing the rate of CsA release fourfold compared with the nanoparticle without a polymer coating.This article is part of the themed issue 'Soft interfacial materials: from fundamentals to formulation'.

Rapid Self-Assembly of Polymer Nanoparticles for Synergistic Codelivery of Paclitaxel and Lapatinib via Flash NanoPrecipitation

“…Co-encapsulating PTX and LAP into nanoparticles resulted in a decrease in the cumulative drug release of LAP but the drug release was comparable for PTX to single-drug-loaded nanoparticles. The slower burst release of LAP from co-loaded nanoparticles may be attributed to lower drug loading concentrations compared to LAP NPs resulting in a slower dissolution profile, a phenomenon observed with hydrophobic materials [55]. These results are consistent with previous literature indicating LAP has a slower release profile compared to PTX from polymer micelles [30].…”

Self-Assembly of pH-Labile Polymer Nanoparticles for Paclitaxel Prodrug Delivery: Formulation, Characterization, and Evaluation

“…Additionally, we observe a decrease in cumulative release after 3 h at pH 4 ( Figure S6) similar to previous reports which has been attributed to supersaturation and nanopreciptaiton of drugs in the dialysis media [14,58,59]. Thus, further studies of the stability and release in more biologically relevant media such as full growth medium with serum [14,42,43] as well as biodistribution in vivo to how understand the drug release and prodrug hydrolysis are affected by protein binding are of interest but are outside the scope of this study.…”

“…Notably, comparing the paclitaxel and prodrug at pH 7, prodrug synthesis can affect the release mechanism. Further evaluation of stability and release in more biologically relevant media such as full growth medium with serum [14,42,43] as well as biodistribution in vivo to how understand the drug release and prodrug hydrolysis are affected by protein binding [44] are of interest but are outside the scope of this study.…”

Antioxidant Response Activating nanoParticles (ARAPas) localize to atherosclerotic plaque and locally activate the Nrf2 pathway

“…Various methods exist to determine the release kinetic profile of hydrophobic drugs from nanoparticles 36 , however irrespective of the method, the underlying assumption is that the experiment satisfies sink conditions, where the volume of medium must be at least three times that required to form a saturated solution of the drug. This condition is commonly not satisfied 37,38 , as for highly insoluble drugs, such as CDDOMe, this can be quite challenging due to large volumes of release medium required and subsequent difficulties analyzing low concentrations of drug. Abouelmagd and co-workers illustrated the issues with two main methods (dialysis and centrifugation) leading to different conclusions of paclitaxel release from nanoparticles 38 .…”