Oral delivery of nanoparticle-based vaccines

Marasini, Nirmal; Skwarczynski, Mariusz; Tóth, István

doi:10.1586/14760584.2014.936852

Cited by 131 publications

(103 citation statements)

References 121 publications

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“…The rate of NM agglomeration in different vehicles is affected by the pH value of the respective environment (Wohlleben et al 2013). In the GT, the intraluminal pH changes rapidly from being highly acidic in the stomach to about pH 6 in the duodenum from where it gradually increases to about pH 7.4 in the terminal ileum (Marasini et al 2014). Both homogeneous agglomeration (NM-NM) and heterogeneous agglomeration (NM with dissolved organics-'protein corona') contribute to increased diameters.…”

Section: Summary Of the Conclusion From The Oral Exposure Studiesmentioning

confidence: 99%

Nanomaterial translocation–the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs–a review

Kermanizadeh

Balharry

Wallin

et al. 2015

Critical Reviews in Toxicology

138

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Engineered nanomaterials (NMs) offer great technological advantages but their risks to human health are still not fully understood. An increasing body of evidence suggests that some NMs are capable of distributing from the site of exposure to a number of secondary organs. The research into the toxicity posed by the NMs in these secondary organs is expanding due to the realisation that some materials may reach and accumulate in these target sites. The translocation to secondary organs includes, but is not limited to, the hepatic, central nervous, cardiovascular and renal systems. Current data indicates that pulmonary exposure is associated with low (inhalation route-0.00001-1% of total applied dose-24 h) translocation of virtually insoluble NMs such as iridium, carbon black, gold and polystyrene, while slightly higher translocation has been observed for NMs with either slow (e.g., silver, cerium dioxide and quantum dots) or fast (e.g., zinc oxide) solubility. The translocation of NMs following intratracheal, intranasal and pharyngeal aspiration is higher (up to 10% of administered dose), however the relevance of these routes for risk assessment is questionable. Uptake of the materials from the gastrointestinal tract seems to follow the same pattern as inhalation translocation, whereas the dermal uptake of NMs is generally reported to be low. The toxicological effects in secondary organs include oxidative stress, inflammation, cytotoxicity and dysfunction of cellular and physiological processes. For toxicological and risk evaluation, further information on the toxicokinetics and persistence of NMs is crucial. The overall aim of this review is to outline the data currently available in the literature on the biokinetics, accumulation, toxicity and eventual fate of NMs in order to assess the potential risks posed by NMs to secondary organs.

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Section: Summary Of the Conclusion From The Oral Exposure Studiesmentioning

confidence: 99%

Nanomaterial translocation–the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs–a review

Kermanizadeh

Balharry

Wallin

et al. 2015

Critical Reviews in Toxicology

138

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“…Chitosan solubility, degradation and toxicity can also be tailored via chemical modification with other hydrophilic moieties [76]. In one example, chitosan was conjugated to amino acids such as L-leucine to provide a potentially improved pulmonary delivery system for the model drug diltiazem [77].…”

Section: Chitosan-drug Conjugatesmentioning

confidence: 99%

Polymer-drug conjugates as inhalable drug delivery systems: A review

Marasini

Haque

Kaminskas

2017

Current Opinion in Colloid & Interface Science

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Abstract:Accelerating interest by the pharmaceutical industry in the identification and development of less invasive routes of nanomedicine administration, coupled with defined efforts to improve the treatment of respiratory diseases through inhaled drug administration has fuelled growing interests in inhalable polymer-drug conjugates. Polymer-drug conjugates can alter the pharmacokinetics profile of the loaded drug after inhaled administration and enable the controlled and sustained exposure of the lungs to drugs when compared to the inhaled or oral administration of the drug alone. However, the major concern with the use of inhalable polymer-drug conjugates is their biocompatibility and long-term safety with the lungs, which is closely linked to their retention time in the lungs. A detailed understanding about the pharmacokinetics, lung disposition, clearance and safety of inhaled polymer-drug conjugates with significant translational potential is therefore required. This review therefore provides a comprehensive summary of the latest developments on several types of polymer-drug conjugates that are currently being explored as inhalable drug delivery systems. Finally, the current status and future perspective of the polymer-drug conjugates is also discussed with a focus on current knowledge gaps. Graphical abstract:

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“…Chemical modification strategies including mutagenesis, proteinylation, glycosylation, PEGylation and prodrugs as well as formulation strategies based on the use of absorption enhancers like nanoparticles, microspheres, liposomes and emulsions, have been used to increase the bioavailability to between 1–2% [13–21]. This threshold allowed for the development of oral vaccines using hydrogel-carriers and nanoparticle-based techniques to protect the antigen from the hostile environment of the GI tract [20,22–24]. In this article we focus on new device-based strategies for drug delivery, which use physical means of tissue interaction coupled with chemical modifications in order to supply protein drugs with higher and narrower dose requirements than vaccines.…”

Section: Introductionmentioning

confidence: 99%

Oral delivery of biologics using drug-device combinations

Caffarel–Salvador

Abramson

Langer

et al. 2017

Current Opinion in Pharmacology

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Orally administered devices could enable the systemic uptake of biologic therapeutics by engineering around the physiological barriers present in the gastrointestinal (GI) tract. Such devices aim to shield cargo from degradative enzymes and increase the diffusion rate of medication through the GI mucosa. In order to achieve clinical relevance, these designs must significantly increase systemic drug bioavailability, deliver a clinically relevant dose and remain safe when taken frequently. Such an achievement stands to reduce our dependence on needle injections, potentially increasing patient adherence and reducing needle-associated complications. Here we discuss the physical and chemical constraints imposed by the gastrointestinal organs and use these to develop a set of boundary conditions on oral device designs for the delivery of macromolecules. We critically examine how device size affects the rate of intestinal obstruction and hinders the loading capacity of poorly soluble protein drugs. We then discuss how current orally administered devices could solve the problem of tissue permeation and conclude that these physical methods stand to provide an efficacious alternative to the classic hypodermic needle.

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Oral delivery of nanoparticle-based vaccines

Cited by 131 publications

References 121 publications

Nanomaterial translocation–the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs–a review

Nanomaterial translocation–the biokinetics, tissue accumulation, toxicity and fate of materials in secondary organs–a review

Polymer-drug conjugates as inhalable drug delivery systems: A review

Oral delivery of biologics using drug-device combinations

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