In vitro uptake evaluation in Caco-2 cells and in vivo results in diabetic rats of insulin-loaded PLGA nanoparticles

Reix, Nathalie; Parat, Audrey; Seyfritz, E.; Werf, Remmelt van der; Epure, V.; Ebel, Nicolas; Danicher, L.; Marchioni, Eric; Jeandidier, N.; Pinget, M.; Frère, Y.; Sigrist, S.

doi:10.1016/j.ijpharm.2012.08.024

Cited by 83 publications

(35 citation statements)

References 40 publications

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“…34,35 The fraction of PLGA nanoparticles entrapped in lysosomes may suffer from degradation, whereas the others transported to the transGolgi network can be packaged into secretory vesicles for exocytosis through fusion with the basolateral membrane. 36 Panyam et al 37 suggested a rapid endolysosomal escape into the cytosol by PLGA nanoparticles, due to their selective reversal of the surface charge (from anionic to cationic) in the acidic endolysosomal compartment. The similar phenomenon of endolysosomal escape was also reported for chitosanmodified iron oxide nanoparticles, 38 which probably results from the "proton-sponge" effect.…”

Section: Dovepressmentioning

confidence: 99%

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Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4

Wang

Zhang²,

Jiao³

et al. 2013

IJN

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Background: Exendin-4 is an incretin mimetic agent approved for type 2 diabetes treatment. However, the required frequent injections restrict its clinical application. Here, the potential use of chitosan-coated poly (d,l-lactide-co-glycolide) (CS-PLGA) nanoparticles was investigated for intestinal delivery of exendin-4. Methods and results: Nanoparticles were prepared using a modified water-oil-water (w/o/w) emulsion solvent-evaporation method, followed by coating with chitosan. The physical properties, particle size, and cell toxicity of the nanoparticles were examined. The cellular uptake mechanism and transmembrane permeability were performed in Madin-Darby canine kidney-cell monolayers. Furthermore, in vivo intraduodenal administration of exendin-4-loaded nanoparticles was carried out in rats. The PLGA nanoparticle coating with chitosan led to a significant change in zeta potential, from negative to positive, accompanied by an increase in particle size of ∼30 nm. Increases in both the molecular weight and degree of deacetylation of chitosan resulted in an observable increase in zeta potential but no apparent change in the particle size of ∼300 nm. Both unmodified PLGA and chitosan-coated nanoparticles showed only slight cytotoxicity. Use of different temperatures and energy depletion suggested that the cellular uptake of both types of nanoparticles was energy-dependent. Further investigation revealed that the uptake of PLGA nanoparticles occurred via caveolin-mediated endocytosis and that of CS-PLGA nanoparticles involved both macropinocytosis and clathrin-mediated endocytosis, as evidenced by using endocytic inhibitors. However, under all conditions, CS-PLGA nanoparticles showed a greater potential to be transported into cells, as shown by flow cytometry and confocal microscopy. Transmembrane permeability analysis showed that unmodified and modified PLGA nanoparticles could improve the transport of exendin-4 by up to 8.9-and 16.5-fold, respectively, consistent with the evaluation in rats. Conclusion:The chitosan-coated nanoparticles have a higher transport potential over both free drug and unmodified particles, providing support for their potential development as a candidate oral delivery agent for exendin-4.

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Section: Dovepressmentioning

confidence: 99%

“…26 The improved P app value may have resulted from the exocytosis of nanoparticles following endolysosomal escape or the exocytosis of exendin-4 released from nanoparticles into cytoplasm. 36,37 Further investigation is needed to illustrate the detailed mechanism.…”

Section: Dovepressmentioning

confidence: 99%

Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4

Wang

Zhang²,

Jiao³

et al. 2013

IJN

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“…These monomers are endogenous, and can be metabolized by cells via Krebs cycle [4]. Given the recent advances in synthesis and surface modification technologies, PLGA can be fine tuned to modify their size, loading (nucleic acid [5], drugs [6], or proteins [7] have been vectorized so far), degradation, and the shell of particles. Due to their biodegradability, PLGA particles are also used to ensure a controlled, sustained release of drugs [8].…”

Section: Introductionmentioning

confidence: 99%

PLGA-Based Nanoparticles: a Safe and Suitable Delivery Platform for Osteoarticular Pathologies

et al. 2015

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“…Poly(lactide-co-glycolide) (PLGA) is widely studied for biological applications owing to their biodegradability and biocompatibility Lassalle & Ferreira 2010;Reix et al, 2012). Generally speaking, the PLGA copolymers were synthesized from lactic acid and glycolic acid through the ring-opening polymerization.…”

Section: Plgamentioning

confidence: 99%

A review of biodegradable polymeric systems for oral insulin delivery

Luo

Xiong

Tian³

et al. 2015

Drug Delivery

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Currently, repeated routine subcutaneous injections of insulin are the standard treatment for insulin-dependent diabetic patients. However, patients' poor compliance for injections often fails to achieve the stable concentration of blood glucose. As a protein drug, the oral bioavailability of insulin is low due to many physiological reasons. Several carriers, such as macromolecules and liposomes have been used to deliver drugs in vivo. In this review article, the gastrointestinal barriers of oral insulin administration are described. Strategies for increasing the bioavailability of oral insulin, such absorption enhancers, enzyme inhibitors, enteric coatings are also introduced. The potential absorption mechanisms of insulin-loaded nanoparticles across the intestinal epithelium, including intestinal lymphatic route, transcellular route and paracellular route are discussed in this review. Natural polymers, such as chitosan and its derivates, alginate derivatives, g-PGA-based materials and starch-based nanoparticles have been exploited for oral insulin delivery; synthetic polymers, such as PLGA, PLA, PCL and PEA have also been developed for oral administration of insulin. This review focuses on recent advances in using biodegradable natural and synthetic polymers for oral insulin delivery along with their future prospects.

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In vitro uptake evaluation in Caco-2 cells and in vivo results in diabetic rats of insulin-loaded PLGA nanoparticles

Cited by 83 publications

References 40 publications

Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4

Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4

PLGA-Based Nanoparticles: a Safe and Suitable Delivery Platform for Osteoarticular Pathologies

A review of biodegradable polymeric systems for oral insulin delivery

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