In Vitro Release Mechanisms of Doxorubicin From a Clinical Bead Drug-Delivery System

Abstract

The release rate of doxorubicin (DOX) from the drug-delivery system (DDS), DC Bead, was studied by 2 miniaturized in vitro methods: free-flowing and sample reservoir. The dependencies of the release mechanisms on in vitro system conditions were investigated experimentally and by theoretical modeling. An inverse relationship was found between release rates and bead size, most likely due to the greater total surface area. The release rates correlated positively with temperature, release medium volume, and buffer strength, although the release medium volume had larger effect than the buffer strength. The sample reservoir method generated slower release rates, which described the in vivo release profile more accurately than the free-flowing method. There was no difference between a pH of 6.3 or 7.4 on the release rate, implying that the slightly acidic tumor microenvironment is less importance for drug release. A positive correlation between stirring rate and release rate for all DDS sizes was observed, which suggests film controlled release. Theoretical modeling highlighted the influence of local equilibrium of protonation, self-aggregation, and bead material interactions of DOX. The theoretical release model might describe the observed larger sensitivity of the release rate to the volume of the release medium compared to buffer strength. A combination of miniaturized in vitro methods and theoretical modeling are useful to identify the important parameters and processes for DOX release from a micro gel-based DDS.

Dexibuprofen Biodegradable Nanoparticles: One Step Closer towards a Better Ocular Interaction Study

“…As expected, DXI free is released after 150 min. The release best fit was a one-phase association, meaning that the release is proportional to the DXI concentration with a half-life of 29 min [38]. This fast release implies that several administrations would be necessary in order to prevent and treat the inflammation associated with several pathologies and associated with surgical procedures.…”

Review of the Development of Methods for Characterization of Microspheres for Use in Embolotherapy: Translating Bench to Cathlab

“…[32a,52b,87] This method, however, also suffers from limitations as some products have been shown to lose mass due to the rate of flow of the eluent through the microsphere mass and incomplete drug release has also been reported, which is an artifact of the method rather than a property of the DEB under study. [32a,87c] Others have described the use of two miniaturized in vitro methods based upon a free‐flowing or sample reservoir setup that allows release rates to be measured under different conditions with reduced amounts of sample, release medium, and waste . They proposed the low volume of in vitro release medium used may better correlate to the in vivo situation due to the low availability of releasing medium at the target site .…”

“…[32a,87c] Others have described the use of two miniaturized in vitro methods based upon a free‐flowing or sample reservoir setup that allows release rates to be measured under different conditions with reduced amounts of sample, release medium, and waste . They proposed the low volume of in vitro release medium used may better correlate to the in vivo situation due to the low availability of releasing medium at the target site . Recently, a modified flow‐through method has been described that uses an occluded mass of microspheres to emulate the embolization and can be adapted to take into account dimensional changes in the microspheres during elution .…”

Synthesis and Characterization of cryogel microcarriers for sustained local delivery of anticancer therapeutics to Glioblastoma multiforme

“…Release studies for loaded doxorubicin propose that an ion-exchange mechanism might be involved in drug elution to the surrounding environment (Lewis et al 2006). Based on this similar mode of action, Ahnfelt et al (Ahnfelt et al 2016) Due to their unique property to bind cationic drugs via ionizable functional groups, sulfonatecontaining hydrogels have been gaining status in sustained and local delivery techniques in areas such as skin substitution, cartilage tissue engineering, and treatment of joint diseases (Liang et al 2016).…”

“…Loading and release experimentations were performed considering the five structurally different types of SPA-PEGDA based cryogel microcarriers, specifically PEGDA, SPA to PEGDA (2:8), SPA to PEGDA (4:6), SPA to PEGDA (6:4), and SPA to PEGDA (8:2). Doxorubicin was chosen as a model drug as it is a commonly used anti-cancer drug that has been under investigation by the FDA for more than three decades (Ahnfelt et al 2016). Doxorubicin is assumed to be slightly positively charged due to its amine group functionality.…”