Reticuloendothelial System Pre-Block Strategy to Improve Tumor Targeting Efficacy for Hyaluronic Acid Related Drug Delivery System
Hyaluronic acid (HA) is widely used in many tumor targeting drug delivery systems (TDDS) due to its biocompatibility and modifiability. Moreover, HA receptors are over-expressed on many tumor cells. However, the clearance of the HA-related TDDS by the reticuloendothelial system (RES)
need urgent consideration on account of the high affinity between HA and related receptors in RES. A pre-block strategy before TDDS administration had been designed to overcome RES clearance. In order to avoid the rapid RES clearance and further improve tumor targeting efficiency for HA-related
TDDS, we designed a novel strategy of selectively pre-blocking HA receptors in RES by injecting HA-coated blank liposome (pre-block formulation) prior to dosing of HA-related TDDS. The molecule weight and surface density of HA in pre-block formulation as well as TDDS, the time interval between
dosing, and the concentration of pre-block formulation, were optimized by a series of in vitro cellular uptake studies in macrophages and 4T1 tumor cell lines, which was further confirmed by in vivo studies. The result shows that that the optimized pre-block formulation can saturate
the RES, by which the RES clearance is weakened and the tumor targeting efficiency for HA-related TDDS is finally improved.
Keywords: ENHANCED TUMOR UPTAKE; HYALURONIC ACID; PRE-BLOCK; RETICULOENDOTHELIAL SYSTEM; TARGETING DRUG DELIVERY SYSTEMS
Document Type: Research Article
Publication date: 01 October 2018
- Journal of Biomedical Nanotechnology (JBN) is a peer-reviewed multidisciplinary journal providing broad coverage in all research areas focused on the applications of nanotechnology in medicine, drug delivery systems, infectious disease, biomedical sciences, biotechnology, and all other related fields of life sciences.
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