Multimeric peptide-based PEG nanocarriers with programmable elimination properties.
In the current study, the design, synthetic feasibility and biochemical characterization of biodegradable peptidic PEG-based nanocarriers are described. The components were selected to influence the body elimination pathway upon nanocarrier biodegradation. Two prototypical nanocarriers were prepared using non-PEGylated and PEGylated peptidic cores [CH(3)CO-(Lys-betaAla-betaAla)(X)-Cys-CONH(2) (X=2, 4)]. A homodimeric nanocarrier with 4 copies of fluorescein-PEG5kDa was synthesized by linking two PEGylated peptidic cores (X=2) using a disulfide bond. A dual labeled heterodimeric nanocarrier with 2 copies of fluorescein-PEG5kDa and 4 copies of Texas Red was also synthesized. Optimum conditions for linking imaging agents, PEG, or a peptidic core to a peptidic core were determined. Significantly higher yields (69% versus 30%) of the PEGylated peptidic core were obtained by using 2 copies of beta-alanine as a spacer along with increasing DMSO concentrations, which resulted in reduced steric hindrance. Stoichiometric addition of the components was also demonstrated and found to be important for reducing polydispersity. Nanocarrier biodegradation was evaluated in simulated intracellular and extracellular/blood environments using 3 mm and 10 microm glutathione in buffer, respectively. The nanocarrier was 9-fold more stable in the extracellular environment. The results suggest selective intracellular degradation of the nanocarrier into components with known body elimination pathways.
Gunaseelan
Simi
S
Department of Pharmaceutics, Rutgers University, NJ 08854, USA.
Pooyan
Shahriar
S
Chen
Peiming
P
Samizadeh
Mahta
M
Palombo
Matthew S
MS
Stein
Stanley
S
Zhang
Xiaoping
X
Sinko
Patrick J
PJ
D020341:Absorbable Implants; D001826:Body Fluids / Q000737:chemistry*; D020099:Coated Materials, Biocompatible / Q000737:chemistry*; D019281:Dimerization; D004337:Drug Carriers / Q000737:chemistry*; D008422:Materials Testing; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D010455:Peptides; D011092:Polyethylene Glycols