Oral delivery of proteins by biodegradable nanoparticles

Bakhru, Sasha; Furtado, Stacia; Morelló, A; Mathiowitz, Edith

doi:10.1016/j.addr.2013.04.006

Cited by 164 publications

(102 citation statements)

References 88 publications

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“…17 It was also reported that the uptake and translocation of the polymer-based particles in the small intestine occur rapidly in less than an hour after administration. 17 The polymers used in oral drug delivery can be widely classified as either hydrophilic or hydrophobic. The hydrophobic group comprises poly (esters), poly (cyanoacrylate), poly (orthoesters) and poly (phosphazenes).…”

Section: Importance Of Oral Deliverymentioning

confidence: 99%

“…16 The absorption of polymer based oral drug delivery systems is dependent on properties such as size, surface chemistry, regiospecificity of a particle in the small intestine, the bio/-mucoadhesive property of the polymer, and permeation enhancement, among other factors. 17 Polymer-based oral drug delivery systems primarily follow the following 3 routes for absorption through GI barrier: (1) through M cells; (2) via enterocyte mediated transcytosis; (3) via the paracellular route. 17 It was also reported that the uptake and translocation of the polymer-based particles in the small intestine occur rapidly in less than an hour after administration.…”

Section: Importance Of Oral Deliverymentioning

confidence: 99%

“…17 Polymer-based oral drug delivery systems primarily follow the following 3 routes for absorption through GI barrier: (1) through M cells; (2) via enterocyte mediated transcytosis; (3) via the paracellular route. 17 It was also reported that the uptake and translocation of the polymer-based particles in the small intestine occur rapidly in less than an hour after administration. 17 The polymers used in oral drug delivery can be widely classified as either hydrophilic or hydrophobic.…”

Section: Importance Of Oral Deliverymentioning

confidence: 99%

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Poly(amido amine) dendrimers in oral delivery

Yellepeddi

Ghandehari

2016

Tissue Barriers

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Poly(amidoamine) (PAMAM) dendrimers have been extensively investigated for oral delivery applications due to their ability to translocate across the gastrointestinal epithelium. In this Review, we highlight recent advances in the evaluation of PAMAM dendrimers as oral drug delivery carriers. Specifically, toxicity, mechanisms of transepithelial transport, models of the intestinal epithelial barrier including isolated human intestinal tissue model, detection of dendrimers, and surface modification are discussed. We also highlight evaluation of various PAMAM dendrimer-drug conjugates for their ability to transport across gastrointestinal epithelium for improved oral bioavailability. In addition, current challenges and future trends for clinical translation of PAMAM dendrimers as carriers for oral delivery are discussed.

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Section: Importance Of Oral Deliverymentioning

confidence: 99%

Section: Importance Of Oral Deliverymentioning

confidence: 99%

Section: Importance Of Oral Deliverymentioning

confidence: 99%

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Poly(amido amine) dendrimers in oral delivery

Yellepeddi

Ghandehari

2016

Tissue Barriers

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“…It is also an important strategy in attempts to negotiate the blood-brain barrier (BBB) to treat central nervous system (CNS) disease [56], as well as for the oral delivery of poorly permeable molecules, including peptides and proteins [57]. There appears to be clinical potential for systemically injected targeted NPs using ligands designed to bind receptors overexpressed on cancer cells or on the BBB [58,59], but there is a recognition issue caused by opsoninbased coronas depositing on the surfaces of targeted NPs in the circulation [60].…”

Section: Hca: Cytotoxicity Of Npsmentioning

confidence: 99%

High-content analysis for drug delivery and nanoparticle applications

Brayden

Cryan

Dawson

et al. 2015

Drug Discovery Today

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Publication information Drug Discovery Today, 20 (8): 942-957Publisher Elsevier Item record/more information http://hdl.handle.net/10197/6636 Publisher's statementThis is the author's version of a work that was accepted for publication in Drug Discovery Today. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Drug Discovery Today, 20 (8), (2015 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Page 1 of 26A c c e p t e d M a n u s c r i p t Sally-Ann CryanSally-Ann Cryan has a pharmacy degree and a PhD in pharmaceutics ( Jeremy SimpsonJeremy Simpson carried out his PhD at the University of Warwick, followed postdoctoral work at the Scripps Research Institute in San Diego, and the Imperial Cancer Research Fund in London. After 9 years as a staff member at the European Molecular Biology Laboratory (EMBL) in Heidelberg (Germany), he was appointed as professor of cell biology at UCD, in 2008. He currently applies high-throughput imaging technologies to study subcellular transport pathways and the internalization routes taken by nanoparticles in cells. He runs the UCD Cell Screening Laboratory and is the author of more than 80 publications.High-content analysis (HCA) provides quantitative multiparametric cellular fluorescence data. From its origins in discovery toxicology, it is now addressing fundamental questions in drug delivery. Nanoparticles (NPs), polymers, and intestinal permeation enhancers are being harnessed in drug delivery systems to modulate plasma membrane properties and the intracellular environment. Identifying comparative mechanistic cytotoxicity on sublethal events is crucial to expedite the development of such systems. NP uptake and intracellular routing pathways are also being dissected using chemical and genetic perturbations, with the potential to assess the intracellular fate of targeted and untargeted particles in vitro. As we discuss here, HCA is set to make a major impact in preclinical delivery research by elucidating the intracellular pathways of NPs and the in vitro mechanistic-based toxicology of formulation constituents. A brief recap of cytotoxicity assaysIn vitro cell-based assays have long been used to assess the cytotoxic effects of drug exposure [1]. Cells undergoing acute necrosis swell and lose metabolic capacity, thereby losing the capacity to maintain a barrier to the extracellular space and the ability ...

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“…has attracted more and more attention from pharmaceutical scientists (Trehan & Ali, 1998;Khafagy et al, 2007). Oral dosing, with broad acceptance and cost-effectiveness, has been the focus of most concern to fulfill the expectation of a needle-free insulin treatment (Iyer et al, 2010;Bakhru et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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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Oral delivery of proteins by biodegradable nanoparticles

Cited by 164 publications

References 88 publications

Poly(amido amine) dendrimers in oral delivery

Poly(amido amine) dendrimers in oral delivery

High-content analysis for drug delivery and nanoparticle applications

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

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