Preparation and characterization of insulin-loaded bioadhesive PLGA nanoparticles for oral administration

Zhang, Xiaoyan; Sun, Muzhen; Zheng, Aiping; De-ying, Cao; Bi, Yunqi; Sun, Jin

doi:10.1016/j.ejps.2012.01.002

Cited by 168 publications

(81 citation statements)

References 29 publications

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“…Considering the great potential advantages of the use of chitosan-coated PLGA (CS-PLGA) nanoparticles as carriers, numerous studies have investigated their transport potential in gene, drug, and vaccine delivery, via various administration routes. [16][17][18][19][20][21][22] However, to our knowledge, no study has yet investigated the potential of CS-PLGA nanoparticles for intestinal delivery of exendin-4 or reported the effect of molecular weight and degree of deacetylation on the characteristics of CS-PLGA nanoparticles.…”

Section: Introductionmentioning

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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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: Introductionmentioning

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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“…The advantages of chitosan-modified PLGA-NPs (CS-PLGA-NPs) include decreased burst effect of the encapsulated drug, better cellular adhesion and longer site-retention of NPs (Zhang et al, 2012). Many researchers have evaluated common PLGA-NPs as drug carriers, but only a few have focused on CS-PLGA-NPs.…”

Section: Introductionmentioning

confidence: 99%

Preparation and in vitro evaluation of thienorphine-loaded PLGA nanoparticles

Yang¹,

Xie

Mei³

2014

Drug Delivery

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Poly (D,L-lactic-co-glycolide) nanoparticles (PLGA-NPs) have attracted considerable interest as new delivery vehicles for small molecules, with the potential to overcome issue such as poor drug solubility and cell permeability. However, their negative surface charge decreases bioavailability under oral administration. Recently, cationically modified PLGA-NPs has been introduced as novel carriers for oral delivery. In this study, our aim was to introduce and evaluate the physiochemical characteristics and bioadhesion of positively charged chitosancoated PLGA-NPs (CS-PLGA-NPs), using thienorphine as a model drug. These results indicated that both CS-PLGA-NPs and PLGA-NPs had a narrow size distribution, averaging less than 130 nm. CS-PLGA-NPs was positively charged (+42.1 ± 0.4 mV), exhibiting the cationic nature of chitosan, whereas PLGA-NPs showed a negative surface charge (À2.01 ± 0.3 mV). CS-PLGA-NPs exhibited stronger bioadhesive potency than PLGA-NPs. Furthermore, the transport of thienorphine-CS-PLGA-NPs by Caco-2 cells was higher than thienorphine-PLGA-NPs or thienorphine solution. CS-PLGA-NPs were also found to significantly enhance cellular uptake compared with PLGA-NPs on Caco-2 cells. An evaluation of cytotoxicity showed no increase in toxicity in either kind of nanoparticles during the formulation process. The study proves that CS-PLGA-NPs can be used as a vector in oral drug delivery systems for thienorphine due to its positive surface charge and bioadhesive properties.

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“…The bioadhesive ability of the nanoparticles has been determined through isolated rat colon test and turbidimetric analysis in our research group, and the results indicated that Tat-CS-NPs possessed good colonic bioadhesive ability (data not shown). On the other hand, a-CS might open the tight junctions between epithelial cells enabling entrance of the nanoparticles in paracellular pathway, hence boosted drug absorption (Gulbake & Jain, 2012;Zhang et al, 2012). In addition, the results from drug release in vitro showed that insulin released from PVA-NPs was much faster than those from Tat-CS-NPs and CS-NPs.…”

Section: Discussionmentioning

confidence: 73%

Modified nanoparticles with cell-penetrating peptide and amphipathic chitosan derivative for enhanced oral colon absorption of insulin: preparation and evaluation

et al. 2015

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(2016) Modified nanoparticles with cell-penetrating peptide and amphipathic chitosan derivative for enhanced oral colon absorption of insulin: preparation and evaluation, Drug Delivery, 23:6, 2003-2014, DOI: 10.3109/10717544.2015 AbstractColon is an ideal absorptive site for oral protein and peptide drug (insulin), and yet it poses multiple barriers against the drug absorption, such as the barriers against the drug diffusion from colon lumen toward the absorptive mucosa and permeation across colon epithelium. In this study, modified nanoparticles (Tat-CS-NPs) with cell-penetrating peptide (Tat) and amphipathic chitosan derivative (a-CS) were used as carriers to improve colonic absorption of the drug. With a-CS as emulsifier and poly(lactic-co-glycolic acid) as matrix material, Tat-CS-NPs were prepared and evaluated in vitro/vivo. Using Caco-2 cell monolayers to imitate the colonic epithelial cells, it was found that the cellular uptake amount and transcellular transportation performance of Tat-CS-NPs were much enhanced compared with those of CS-NPs and PVA-NPs. The efficacy evaluation on diabetic rat models demonstrated that the hypoglycemic effect of Tat-CS-NPs loaded with insulin was 6.89 times higher than that of PVANPs, and 1.79 times higher than that of CS-NPs. By gavage of [ 99m Tc] isotope labeled Tat-CS-NPs in mini-pigs and single-photon emission computed tomography (SPECT) on pigs' gastrointestinal tract, it was further proved that the nanoparticles could reach colon and produce pharmacological effect. In conclusion, Tat-CS-NPs as vehicles for colon-specific drug delivery may be an efficient approach to improve oral bioavailability of protein and peptide drugs.

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Preparation and characterization of insulin-loaded bioadhesive PLGA nanoparticles for oral administration

Cited by 168 publications

References 29 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

Preparation and in vitro evaluation of thienorphine-loaded PLGA nanoparticles

Modified nanoparticles with cell-penetrating peptide and amphipathic chitosan derivative for enhanced oral colon absorption of insulin: preparation and evaluation

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