Intranasal administration of elastin-like polypeptide for therapeutic delivery to the central nervous system

Abstract

Bypassing the blood–brain barrier is one of the primary considerations when designing compounds intended to function in the central nervous system (CNS). Intranasal (IN) administration of otherwise blood–brain barrier impermeable molecules can result in high CNS concentrations and low systemic accumulation, indicating that IN administration may be a useful method of delivering therapeutics to the CNS. Elastin-like polypeptide (ELP) is a large, non-immunogenic, highly manipulable biopolymer with extensive evidence supporting its use as a carrier with the ability to improve drug pharmacokinetics and drug targeting. The ability of ELP to reach the CNS via IN administration has been shown previously. Previous studies have also identified the ability of cell penetrating peptides (CPPs) to increase the uptake of molecules in some instances, including via the IN route. Here, we compared and contrasted the biodistribution of ELPs with or without addition of the CPPs Tat or SynB1 via both the IN and intravenous routes. Administration of ELP via the IN route led to significant accumulation in the brain, especially in the olfactory bulbs. When injected intravenously, <3% of the ELP signal was present outside the vascular compartment. This contrasted with IN administration, which resulted in 79% of the fluorescence signal localized outside the vascular space. The fusion of Tat or SynB1 significantly altered the biodistribution of ELP, decreasing the total CNS accumulation following IN administration. The addition of CPPs to ELP increased their retention in the nasal epithelium. These results suggest ELP may represent an effective CNS delivery vector without further modification and that the addition of a CPP significantly influences biodistribution.

Mixed Amphiphilic Polymeric Nanoparticles of Chitosan, Poly(vinyl alcohol) and Poly(methyl methacrylate) for Intranasal Drug Delivery: A Preliminary In Vivo Study

“…administration when compared to i.v. : (i) there was higher accumulation in the brain [ 51 ] and (ii) the accumulation was less spread, enabling targeting of the nanoparticles to more specific CNS regions, which is associated with the nanoparticle properties [ 56 ] and probably with the type of nasal nanoformulation [ 54 ]. After i.n.…”

Intra-vitreal αB crystallin fused to elastin-like polypeptide provides neuroprotection in a mouse model of age-related macular degeneration

“…Further, in this report we demonstrate that ELPs are retained in one target tissue for durations as long as two weeks. In addition, by leveraging intra-vitreal administration the likelihood of off-target drug effects will be minimized as recently reported for intranasal delivery [53]. Previous studies have demonstrated that apoptosis plays an important role in RPE degeneration in NaIO 3 challenged mice, and that αB crystallin has anti-apoptotic effects [4,6,27,35,39].…”

Current and novel polymeric biomaterials for neural tissue engineering

“…ELPs fused with neurotrophin served as a drug depot, limiting neurotrophin loss due to diffusion, and allowed controlled spatio-temporal drug delivery [83]. Moreover, the tuneable characteristics of ELPs allowed intranasal administration aimed at therapeutic delivery of drugs to the CNS [84].…”