Mathematical modeling and parametrical analysis of the temperature dependency of control drug release from biodegradable nanoparticles

Abstract

In this study we describe a mathematical analysis that considers the temperature effects of the controlled drug release process from biodegradable poly-D,L-lactide-co-glycolide (PLGA) nanoparticles.Temperature effects are incorporated and applied to two drug release models. The first one consists of a two-stage release process that considers only simultaneous contributions of initial burst and nanoparticle degradation-relaxation (BR model). The second one is a three release stage model that considers, additionally, a simultaneous drug diffusion (BRD model) step. In these models, the temperature dependency of the release parameters, initial burst constant, k b , the rate of degradationrelaxation constant, k r , time to achieve 50% of release, t max , and effective diffusion coefficient constant (D e ), are determined using mathematical expressions analogous to the Arrhenius equation. The temperature dependent models are used to analyze the release of previously encapsulated Rhodamine 6G dye as a model drug in polyethylene glycol modified PLGA nanoparticles. The experimental data used to develop the mathematical model was obtained from release studies carried out in phosphate buffer pH 7.4 at 37 C, 47 C, and 57 C. Multiphasic release behaviors with an overall increase rate associated with the incubation temperature were observed. The study incorporates a parametrical analysis that can evaluate diverse temperature variation effects of the controlled release parameters for the two models.

Poly(3-Hydroxybutyrate)-Based Nanoparticles for Sorafenib and Doxorubicin Anticancer Drug Delivery

“…Mathematical modeling of triphasic kinetics has been provided by Lucero-Acuña et al [ 44 , 45 ]. The burst and relaxation induced and diffusion-controlled release is expressed in the first, second and third term of the Equation (1), respectively: …”

Polymer-free corticosteroid dimer implants for controlled and sustained drug delivery

“…Modifying drug release kinetics for degradable polymer systems can be achieved through changes to the chemistry of the polymer backbone, polymer molecular weight, and the choice of degradable linkages with differing hydrolytic or enzymatic susceptibility 5 . However, this approach can often yield non-intuitive changes to release kinetics 21 , 72 , requiring significant experimental investigation first in vitro and subsequently in vivo to understand the impact of changes that have been made on release kinetics. In contrast, the systems presented in this work present a practical and simple approach to predicting performance, based on the surface-erosion mediated release kinetics of the corticosteroid dimers.…”

Development of a Model Based on Physical Mechanisms for the Explanation of Drug Release: Application to Diclofenac Release from Polyurethane Films

“…These mechanisms contribute to a part of the global quantity liberated, and each can be affected by the variation of certain factors. Amounts of the drug liberated are limited between 0% and 100% of the global released quantity [ 19 , 20 ]. Therefore, various mechanisms governing drug release need to be adequately investigated.…”