Characterization of polymeric nanoparticles for intravenous delivery: Focus on stability.
The nano-bio interaction has been of increased focus in the past years but very limited results have been obtained for polymeric nanoparticles (NP). Not only is needed to broaden the results obtained with model NP towards other nano-materials used for clinical application but the colloidal stability of NP as a variable consequence of the formation of the protein corona has been significantly understated. The lack and heterogeneity of assays to study NP stability and represent the biological environment call for the standardization of assays to improve the representativeness and comparability of results. In this paper, uncoated and PAH-coated PLGA NP have been prepared and characterized in regard to their potential for intravenous administration. The comparative study of the stability of NP in three media used to represent the biological environment-bovine serum albumin (BSA) solution, mouse and human plasma - revealed that both formulations were unstable in human plasma as opposed to the results obtained for other media. This unexpected behavior in plasmas of different origins could be correlated with a significant variation of the amount of proteins adsorbed to NP and, ultimately, with an approximately 6-fold difference in total protein concentration between the plasma samples. These results suggest that inter-species variation could impact on the colloidal stability of NP and enhance the need to understand the correlation between biological media and identify protocol-related interferences which, altogether, may evidence a relevant factor compromising in vitro- in vivo correlation and the translation of delivery systems aimed at intravenous administration.
Group Genetics of Cognitive Dysfunction, I3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal; ICBAS, Universidade do Porto, Portugal; Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
Claudia L
CL
Oliveira
Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
Francisco
F
Veiga
Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
Carla
C
Varela
Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CNC-Center for Neurosciences and Cell Biology, University of Coimbra, Portugal.
Fernanda
F
Roleira
Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; CNC-Center for Neurosciences and Cell Biology, University of Coimbra, Portugal.
Elisiário
E
Tavares
Group Genetics of Cognitive Dysfunction, I3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal; ICBAS, Universidade do Porto, Portugal.
Isabel
I
Silveira
Group Genetics of Cognitive Dysfunction, I3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal; IBMC-Instituto de Biologia Molecular e Celular, Universidade do Porto, Portugal; Faculty of Pharmacy, University of Coimbra, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal. Electronic address: aribeiro@ff.uc.pt.
Antonio J
AJ
Ribeiro
D061605:Administration, Intravenous; D000327:Adsorption; D000818:Animals; D003102:Colloids / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D015203:Reproducibility of Results; D012710:Serum Albumin, Bovine / Q000737:chemistry
D003102:Colloids; D004337:Drug Carriers; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D012710:Serum Albumin, Bovine; D019344:Lactic Acid
Biological stability; Bovine serum albumin; Mouse and human plasma; Physicochemical characterization; Poly allylamine hydrochloride; Poly(lactic-co-glycolic) acid