Administration strategies for proteins and peptides

Ibraheem, D.; Elaı̈ssari, Abdelhamid; Fessi, Hatem

doi:10.1016/j.ijpharm.2014.10.059

Cited by 90 publications

(70 citation statements)

References 189 publications

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“…Despite this, only a small fraction of currently licensed vaccines are oral formulations due to the inherent obstacles presented by the gastrointestinal system. The induction of a robust protective immune response by oral immunization requires: (i) successful delivery of the intact and active antigen to the intestine, (ii) transport across the mucosal barrier, and (iii) subsequent activation of antigen-presenting cells [14,23,25]. However, the GI tract poses difficulties to each step, including degradation of fragile antigens through the harsh environment in the stomach and requirement of adequate doses to generate immunity instead of tolerance [21,26].…”

Section: Oral Administrationmentioning

confidence: 99%

Current state and challenges in developing oral vaccines

Ramirez

Sharpe

Peppas

2017

Advanced Drug Delivery Reviews

313

275

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While vaccination remains the most cost effective strategy for disease prevention, communicable diseases persist as the second leading cause of death worldwide. There is a need to design safe, novel vaccine delivery methods to protect against unaddressed and emerging diseases. Development of vaccines administered orally is preferable to traditional injection-based formulations for numerous reasons including improved safety and compliance, and easier manufacturing and administration. Additionally, the oral route enables stimulation of humoral and cellular immune responses at both systemic and mucosal sites to establish broader and long-lasting protection. However, oral delivery is challenging, requiring formulations to overcome the harsh gastrointestinal (GI) environment and avoid tolerance induction to achieve effective protection. Here we address the rationale for oral vaccines, including key biological and physicochemical considerations for next-generation oral vaccine design.

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Section: Oral Administrationmentioning

confidence: 99%

Current state and challenges in developing oral vaccines

Ramirez

Sharpe

Peppas

2017

Advanced Drug Delivery Reviews

313

275

View full text Add to dashboard Cite

show abstract

“…Although insulin can be administered through both injection and non-injection routes, the latter generally suffer from low bioavailability. 7,8 However, daily administration of insulin by injection is uncomfortable for patients and can even be dangerous: the injection of excess insulin can result in serious shock responses such as hypoglycemia, syncope, or even death. 9,10 To ameliorate these issues, much effort has been invested in the development of smart drug delivery systems that are able to release insulin in response to changes in the blood glucose level.…”

Section: Introductionmentioning

confidence: 99%

Glucose- and temperature-sensitive nanoparticles for insulin delivery

Wu¹,

Williams²,

Li³

et al. 2017

IJN

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Glucose- and temperature-sensitive polymers of a phenylboronic acid derivative and diethylene glycol dimethacrylate (poly(3-acrylamidophenyl boronic acid- b -diethylene glycol methyl ether methacrylate); p(AAPBA- b -DEGMA)) were prepared by reversible addition–fragmentation chain transfer polymerization. Successful polymerization was evidenced by 1 H nuclear magnetic resonance and infrared spectroscopy, and the polymers were further explored in terms of their glass transition temperatures and by gel permeation chromatography (GPC). The materials were found to be temperature sensitive, with lower critical solution temperatures in the region of 12°C–47°C depending on the monomer ratio used for reaction. The polymers could be self-assembled into nanoparticles (NPs), and the zeta potential and size of these particles were determined as a function of temperature and glucose concentration. Subsequently, the optimum NP formulation was loaded with insulin, and the drug release was studied. We found that insulin was easily encapsulated into the p(AAPBA- b -DEGMA) NPs, with a loading capacity of ~15% and encapsulation efficiency of ~70%. Insulin release could be regulated by changes in temperature and glucose concentration. Furthermore, the NPs were non-toxic both in vitro and in vivo. Finally, the efficacy of the formulations at managing blood glucose levels in a murine hyperglycemic diabetes model was studied. The insulin-loaded NPs could reduce blood glucose levels over an extended period of 48 h. Since they are both temperature and glucose sensitive and offer a sustained-release profile, these systems may comprise potent new formulations for insulin delivery.

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“…[453] This trend is supported by the development of enhanced drug-delivery systems. [454] Given the limitations of unmodified peptides, this is a remarkable trend that indicates the potential of peptidomimetics to reduce peptide-associated drawbacks. In this respect, a more detailed understanding of the advantages and limitations of certain mimicry approaches is crucial for their efficient application.…”

Section: Discussionmentioning

confidence: 99%

Structure‐Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes

et al. 2015

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Protein–protein interactions (PPIs) are involved at all levels of cellular organization, thus making the development of PPI inhibitors extremely valuable. The identification of selective inhibitors is challenging because of the shallow and extended nature of PPI interfaces. Inhibitors can be obtained by mimicking peptide binding epitopes in their bioactive conformation. For this purpose, several strategies have been evolved to enable a projection of side chain functionalities in analogy to peptide secondary structures, thereby yielding molecules that are generally referred to as peptidomimetics. Herein, we introduce a new classification of peptidomimetics (classes A–D) that enables a clear assignment of available approaches. Based on this classification, the Review summarizes strategies that have been applied for the structure-based design of PPI inhibitors through stabilizing or mimicking turns, β-sheets, and helices.

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Administration strategies for proteins and peptides

Cited by 90 publications

References 189 publications

Current state and challenges in developing oral vaccines

Current state and challenges in developing oral vaccines

Glucose- and temperature-sensitive nanoparticles for insulin delivery

Structure‐Based Design of Inhibitors of Protein–Protein Interactions: Mimicking Peptide Binding Epitopes

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