Polymer Chemistry Influences Monocytic Uptake of Polyanhydride Nanospheres

• Published in: Pharmaceutical research 2009-03, Vol.26 (3), p.683-690
• Main Authors: Ulery, Bret D, Phanse, Yashdeep, Sinha, Avanti, Wannemuehler, Michael J, Narasimhan, Balaji, Bellaire, Bryan H
• Format: Article
• Language: English
• Subjects: adjuvants; Antigen-Presenting Cells; Antigens, Surface - administration & dosage; Biochemistry; Biological and medical sciences; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Cell Line; Cellular biology; Chemical Precipitation; chemistry; Decanoic Acids - chemical synthesis; Decanoic Acids - chemistry; Decanoic Acids - pharmacokinetics; Dicarboxylic Acids - chemistry; Drug Carriers - chemical synthesis; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; General pharmacology; Hexanes - chemistry; Humans; immune response; Immunology; Leukocytes; Medical Law; Medical sciences; Microscopy, Confocal; Microscopy, Electron, Scanning; Monocytes - metabolism; Nanoparticles; Nanospheres - chemistry; Particle Size; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; polyanhydride; Polyanhydrides - chemical synthesis; Polyanhydrides - chemistry; Polyanhydrides - pharmacokinetics; Polyesters - chemical synthesis; Polyesters - chemistry; Polyesters - pharmacokinetics; Polymers; Research Paper; Surface Properties; Vaccines - administration & dosage
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-008-9760-7

Purpose To demonstrate that polyanhydride copolymer chemistry affects the uptake and intracellular compartmentalization of nanospheres by THP-1 human monocytic cells. Methods Polyanhydride nanospheres were prepared by an anti-solvent nanoprecipitation technique. Morphology and particle diameter were confirmed via scanning election microscopy and quasi-elastic light scattering, respectively. The effects of varying polymer chemistry on nanosphere and fluorescently labeled protein uptake by THP-1 cells were monitored by laser scanning confocal microscopy. Results Polyanhydride nanoparticles composed of poly(sebacic anhydride) (SA), and 20:80 and 50:50 copolymers of 1,6-bis-(p-carboxyphenoxy)hexane (CPH) anhydride and SA were fabricated with similar spherical morphology and particle diameter (200 to 800 nm). Exposure of the nanospheres to THP-1 monocytes showed that poly(SA) and 20:80 CPH:SA nanospheres were readily internalized whereas 50:50 CPH:SA nanospheres had limited uptake. The chemistries also differentially enhanced the uptake of a red fluorescent protein-labeled antigen. Conclusions Nanosphere and antigen uptake by monocytes can be directly correlated to the chemistry of the nanosphere. These results demonstrate the importance of choosing polyanhydride chemistries that facilitate enhanced interactions with antigen presenting cells that are necessary in the initiation of efficacious immune responses.