TY - JOUR
T1 - Effect of mucoadhesive polymers on the in vitro performance of insulin-loaded silica nanoparticles
T2 - interactions with mucin and biomembrane models
AU - Andreani, Tatiana
AU - Miziara, Leonardo
AU - Lorenzón, Esteban N.
AU - De Souza, Ana Luiza R.
AU - Kiill, Charlene P.
AU - Fangueiro, Joana F.
AU - Garcia, Maria L.
AU - Gremião, Palmira D.
AU - Silva, Amélia M.
AU - Souto, Eliana B.
N1 - Funding Information:
The work was partially supported by Fundação para a Ciência e Tecnologia (FCT, Portugal), namely, the PhD scholarships SFRH/BD/60640/2009 for T. Andreani and SFRH/BD/80335/2011 for J.F. Fangueiro. FCT and FEDER/COMPETE are also acknowledged under the reference PTDC/SAU-FAR/113100/2009 and PEst-C/AGR/UI4033/2014. The authors also acknowledge the support by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and by European Union Funds (FEDER/COMPETE) under the reference FCOMP-01-0124-FEDER-022696. The authors also acknowledge the support by FAPESP for the PhD scholarship for C.P. Kiill under the reference 2012/10174-3 and for E.N. Lorenzón under the reference 140758/2011-9.
Publisher Copyright:
© 2015 Elsevier B.V. All rights reserved.
PY - 2015/6/1
Y1 - 2015/6/1
N2 - The present paper focuses on the development and characterization of silica nanoparticles (SiNP) coated with hydrophilic polymers as mucoadhesive carriers for oral administration of insulin. SiNP were prepared by sol-gel technology under mild conditions and coated with different hydrophilic polymers, namely, chitosan, sodium alginate or poly(ethylene glycol) (PEG) with low and high molecular weight (PEG 6000 and PEG 20000) to increase the residence time at intestinal mucosa. The mean size and size distribution, association efficiency, insulin structure and insulin thermal denaturation have been determined. The mean nanoparticle diameter ranged from 289 nm to 625 nm with a PI between 0.251 and 0.580. The insulin association efficiency in SiNP was recorded above 70%. After coating, the association efficiency of insulin increased up to 90%, showing the high affinity of the protein to the hydrophilic polymer chains. Circular dichroism (CD) indicated that no conformation changes of insulin structure occurred after loading the peptide into SiNP. Nano-differential scanning calorimetry (nDSC) showed that SiNP shifted the insulin endothermic peak to higher temperatures. The influence of coating on the interaction of nanoparticles with dipalmitoylphosphatidylcholine (DPPC) biomembrane models was also evaluated by nDSC. The increase of ΔH values suggested a strong association of non-coated SiNP and those PEGylated nanoparticles coated with DPPC polar heads by forming hydrogen bonds and/or by electrostatic interaction. The mucoadhesive properties of nanoparticles were examined by studying the interaction with mucin in aqueous solution. SiNP coated with alginate or chitosan showed high contact with mucin. On the other hand, non-coated SiNP and PEGylated SiNP showed lower interaction with mucin, indicating that these nanoparticles can interdiffuse across mucus network. The results of the present work provide valuable data in assessing the in vitro performance of insulin-loaded SiNP coated with mucoadhesive polymers.
AB - The present paper focuses on the development and characterization of silica nanoparticles (SiNP) coated with hydrophilic polymers as mucoadhesive carriers for oral administration of insulin. SiNP were prepared by sol-gel technology under mild conditions and coated with different hydrophilic polymers, namely, chitosan, sodium alginate or poly(ethylene glycol) (PEG) with low and high molecular weight (PEG 6000 and PEG 20000) to increase the residence time at intestinal mucosa. The mean size and size distribution, association efficiency, insulin structure and insulin thermal denaturation have been determined. The mean nanoparticle diameter ranged from 289 nm to 625 nm with a PI between 0.251 and 0.580. The insulin association efficiency in SiNP was recorded above 70%. After coating, the association efficiency of insulin increased up to 90%, showing the high affinity of the protein to the hydrophilic polymer chains. Circular dichroism (CD) indicated that no conformation changes of insulin structure occurred after loading the peptide into SiNP. Nano-differential scanning calorimetry (nDSC) showed that SiNP shifted the insulin endothermic peak to higher temperatures. The influence of coating on the interaction of nanoparticles with dipalmitoylphosphatidylcholine (DPPC) biomembrane models was also evaluated by nDSC. The increase of ΔH values suggested a strong association of non-coated SiNP and those PEGylated nanoparticles coated with DPPC polar heads by forming hydrogen bonds and/or by electrostatic interaction. The mucoadhesive properties of nanoparticles were examined by studying the interaction with mucin in aqueous solution. SiNP coated with alginate or chitosan showed high contact with mucin. On the other hand, non-coated SiNP and PEGylated SiNP showed lower interaction with mucin, indicating that these nanoparticles can interdiffuse across mucus network. The results of the present work provide valuable data in assessing the in vitro performance of insulin-loaded SiNP coated with mucoadhesive polymers.
KW - Biomembranes
KW - Insulin
KW - Mucoadhesion
KW - Oral delivery
KW - Silica nanoparticles
KW - Thermal denaturation
UR - http://www.scopus.com/inward/record.url?scp=84926472510&partnerID=8YFLogxK
U2 - 10.1016/j.ejpb.2015.03.027
DO - 10.1016/j.ejpb.2015.03.027
M3 - Article
C2 - 25843239
AN - SCOPUS:84926472510
SN - 0939-6411
VL - 93
SP - 118
EP - 126
JO - European Journal of Pharmaceutics and Biopharmaceutics
JF - European Journal of Pharmaceutics and Biopharmaceutics
ER -