Abstract
Poly(amidoamine)s (PAAs) are water-soluble synthetic polymers designed to be biodegradable and biocompatible. Moreover, they display membrane disruptive properties in response to a decrease in pH. This attribute confers PAAs with endosomolytic properties in vitro and in vivo. A model system was developed to quantify their ability to promote the endosomal escape of macromolecules that may be interesting as therapeutic agents. Here, two PAAs (ISA 1 and 4) were incubated with B16F10 cells in vitro together with two non-permeant toxins: either ricin A-chain (RTA) or gelonin. The relatively non-toxic PAAs ISA 1 and 4 (IC 50>1.5 mg/ml) restored activity to the inherently inert toxins. The IC 50 values for the ISA 1/RTA and ISA 1/gelonin combinations were 0.65±0.05 and 0.55±0.12 mg/ml, respectively. Similarly, when ISA 4 was incubated with a non-toxic combination of RTA and gelonin the IC 50 value decreased to 0.57±0.03 and 0.43±0.26 mg/ml, respectively. In contrast, the neutral polymer dextran and the PAA ISA 22 were unable to mediate this effect. These observations suggest that specific PAA–toxin combinations warrant further development as novel therapeutics.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
