LifeTein’s cysteine-containing peptides helped researchers better understand the effect peptide physicochemical properties have on the pharmacokinetic profiles of the nanoparticles they are attached to. Better understanding and control of these effects is invaluable for future engineering design of many types of therapeutic nanomaterials, including for treatment of traumatic brain injuries (TBI).
Nanoparticles’ Physicochemical Properties Influenced by Peptides
Scientists at the University of California were keen on finding out what exact physicochemical properties in peptides affect the pharmacokinetics of nanoparticles designed for treating TBI. Nanoparticles are a convenient means of therapeutic drug delivery, as they can exhibit different pharmacokinetic profiles from the drug cargo in their core. This experiment analyzed how functionalizing the nanoparticles with PEG and an array of peptides with varying physicochemical properties, provided by LifeTein, contribute to the biodistribution in vivo, using a mouse model of TBI.
Results showed that the biodistribution of the modified nanoparticles varied mainly as a result of the charge of the peptides attached; basic peptides resulted in restricted distributions in the brain via convection-enhanced delivery (CED), as well as elevated off-target organ accumulation resulting in a decrease in brain accumulation when using systemic administration. In comparison, nanoparticles modified with acidic, zwitterionic, or neutral peptides demonstrated less restricted distribution in the brain via CED, and increased accumulation in injured vs. uninjured brain tissue after systemic administration.
This study suggests that the charge of peptides should be greatly taken into account when designing nanoparticles with peptide-modified surfaces. Peptides offer a great way to influence the biological interactions of nanoparticles, and understanding what physicochemical properties contribute to said influence will further advance the use of therapeutic nanoparticles in treatments like TBI.
Reference: Waggoner, L.E., Madias, M.I., Hurtado, A.A. et al. Pharmacokinetic Analysis of Peptide-Modified Nanoparticles with Engineered Physicochemical Properties in a Mouse Model of Traumatic Brain Injury. AAPS J 23, 100 (2021). https://doi.org/10.1208/s12248-021-00626-5