Controlled SLN Delivery by Thermoresponsive In-situ Forming Erodible Gels; A Whole-body and Organ Imaging Study

Abstract

Background: Nanoparticles (NPs) suffer from rapid clearance from body and require frequent dosing if long treatment is required.

Method: In order to solve this problem for solid lipid nanoparticles (SLN) and prolong their action, SLNs were incorporated into thermo-responsive Poloxamer sol-gels and their fate was investigated invivo and in-vitro using a near infrared lipophilic fluorescent dye; dialkylcarbocyanin [1]. Leakage test, release of intact SLNs from sol-gel and SLN size and zeta potential were investigated. Biodistribution of DiR formulations (solution, free SLN and SLN-Gel) was investigated by whole-body and ex-vivo organ imaging after intraperitoneal injection in mice. SLN showed particle size of about 165 nm and a negative zeta potential of about -36 mV.

Results: Leakage studies indicated that fluorescent probe does not release from SLNs. Imaging results revealed a steady profile for SLN-Gel over time, while the fluorescence intensity of solution and free SLN showed a burst followed by rapid clearance. Results also showed that SLN release occurs after gel erosion and follows a zero order profile.

Conclusion: Our results indicate that NP-incorporated gel can be used to control the release of SLNs from application site and prolong their action in a sustained manner.

Keywords: Controlled release; SLN; fluorescence reflectance imaging; in-situ forming gels; solid lipid nanoparticle; thermoresponsive; tissue imaging; whole-body imaging..