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Oral delivery of peptide drugs using nanoparticles self-assembled by poly(gamma-glutamic acid) and a chitosan derivative functionalized by trimethylation.
- Source :
-
Bioconjugate chemistry [Bioconjug Chem] 2008 Jun; Vol. 19 (6), pp. 1248-55. Date of Electronic Publication: 2008 Jun 03. - Publication Year :
- 2008
-
Abstract
- In the study, chitosan (CS) was conjugated with trimethyl groups for the synthesis of N-trimethyl chitosan (TMC) polymers with different degrees of quaternization. Nanoparticles (NPs) self-assembled by the synthesized TMC and poly(gamma-glutamic acid) (gamma-PGA, TMC/gamma-PGA NPs) were prepared for oral delivery of insulin. The loading efficiency and loading content of insulin in TMC/gamma-PGA NPs were 73.8 +/- 2.9% and 23.5 +/- 2.1%, respectively. TMC/gamma-PGA NPs had superior stability in a broader pH range to CS/gamma-PGA NPs; the in vitro release profiles of insulin from both test NPs were significantly affected by their stability at distinct pH environments. At pH 7.0, CS/gamma-PGA NPs became disintegrated, resulting in a rapid release of insulin, which failed to provide an adequate retention of loaded insulin, while the cumulative amount of insulin released from TMC/gamma-PGA NPs was significantly reduced. At pH 7.4, TMC/gamma-PGA NPs were significantly swelled and a sustained release profile of insulin was observed. Confocal microscopy confirmed that TMC40/gamma-PGA NPs opened the tight junctions of Caco-2 cells to allow the transport of insulin along the paracellular pathway. Transepithelial-electrical-resistance measurements and transport studies implied that CS/gamma-PGA NPs can be effective as an insulin carrier only in a limited area of the intestinal lumen where the pH values are close to the p K a of CS. In contrast, TMC40/gamma-PGA NPs may be a suitable carrier for transmucosal delivery of insulin within the entire intestinal tract.
- Subjects :
- Administration, Oral
Animals
Caco-2 Cells
Drug Carriers chemical synthesis
Electric Impedance
Enzyme-Linked Immunosorbent Assay
Epithelial Cells metabolism
Humans
Hydrogen-Ion Concentration
Insulin administration & dosage
Methylation
Models, Molecular
Molecular Conformation
Polyglutamic Acid chemistry
Polymers chemical synthesis
Solubility
Chitosan chemistry
Drug Carriers chemistry
Insulin chemistry
Insulin pharmacology
Nanoparticles chemistry
Polyglutamic Acid analogs & derivatives
Polymers chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1520-4812
- Volume :
- 19
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Bioconjugate chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 18517235
- Full Text :
- https://doi.org/10.1021/bc800076n