Chitosan-modified porous silicon microparticles for enhanced permeability of insulin across intestinal cell monolayers.
Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi microparticles to enhance the intestinal permeation of insulin. Surface modification with CS led to significant increase in the interaction of PSi microparticles with Caco-2/HT-29 cell co-culture monolayers. Compared to pure insulin, the CS-conjugated microparticles significantly improved the permeation of insulin across the Caco-2/HT-29 cell monolayers, with ca. 20-fold increase in the amount of insulin permeated and ca. 7-fold increase in the apparent permeability (P(app)) value. Moreover, among all the investigated particles, the CS-conjugated microparticles also showed the highest amount of insulin associated with the mucus layer and the intestinal Caco-2 cells and mucus secreting HT-29 cells. Our results demonstrate that CS-conjugated AnnUnTHCPSi microparticles can efficiently enhance the insulin absorption across intestinal cells, and thus, they are promising microsystems for the oral delivery of proteins and peptides across the intestinal cell membrane.
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014, University of Helsinki, Finland.
Neha
N
Shrestha
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014, University of Helsinki, Finland.
Mohammad-Ali
MA
Shahbazi
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014, University of Helsinki, Finland; INEB - Instituto de Engenharia Biomédica, NewTherapies Group, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; ICBAS - Instituto Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal.
Francisca
F
Araújo
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014, University of Helsinki, Finland.
Hongbo
H
Zhang
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014, University of Helsinki, Finland; Laboratory of Industrial Physics, Department of Physics and Astronomy, FI-20014, University of Turku, Finland.
Ermei M
EM
Mäkilä
Laboratory of Materials Chemistry and Chemical Analysis, Department of Chemistry, University of Turku, FI-20014 Turku, Finland.
Jussi
J
Kauppila
INEB - Instituto de Engenharia Biomédica, NewTherapies Group, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; IINFACTS - Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Superior de Ciências da Saúde-Norte, Department of Pharmaceutical Sciences, CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal.
Bruno
B
Sarmento
Laboratory of Industrial Physics, Department of Physics and Astronomy, FI-20014, University of Turku, Finland.
Jarno J
JJ
Salonen
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014, University of Helsinki, Finland.
Jouni T
JT
Hirvonen
Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, FI-00014, University of Helsinki, Finland. Electronic address: helder.santos@helsinki.fi.
Hélder A
HA
Santos
D018938:Caco-2 Cells; D002470:Cell Survival; D048271:Chitosan / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D019073:HT29 Cells; D006801:Humans; D007328:Insulin / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000187:drug effects*; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D010539:Permeability; D016062:Porosity; D012825:Silicon / Q000737:chemistry*; D013499:Surface Properties
D007328:Insulin; D048271:Chitosan; D012825:Silicon
Cell monolayers; Chitosan; Diabetes; Insulin; Microparticles; Porous silicon