Protein drug delivery: current dosage form profile and formulation strategies

Geraldes, Danilo Costa; Beraldo-de-Araújo, Viviane Lucia; Pardo, Boris Odelion Pichihua; Pessoa, Adalberto; Stephano, Marco Antônio; Nascimento, Laura de Oliveira

doi:10.1080/1061186x.2019.1669043

Cited by 30 publications

(12 citation statements)

References 131 publications

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“…However, access to the cytosol is often limited in efficiency, because these systems are generally taken up by endocytosis through a range of mechanisms . Endocytic uptake entraps particles in vesicles (endosomes) that sequester them from the cytosol, ultimately leading to either endo/lysosomal degradation or exocytosis. , Choice of carrier material, formulation, and treatment conditions are critical considerations for effective delivery, and all contribute to both cellular uptake and intracellular distribution. − Engineered delivery vehicles can promote endosomal “escape” through various methods of endosomal rupture, − but recent reports estimate that even utilizing these methods <10% of endosomally delivered cargo can be expected to enter the cytosol. , Recently, vehicles capable of nonendosomal uptake through direct cytosolic entry have been reported with highly efficient protein delivery, providing a potential alternative pathway. , Distinguishing cytosolic access from endosomal entrapment however, is a critically important yet often overlooked checkpoint in the development of effective intracellular delivery systems. , …”

Section: Introductionmentioning

confidence: 99%

Protein Delivery: If Your GFP (or Other Small Protein) Is in the Cytosol, It Will Also Be in the Nucleus

et al. 2021

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Intracellular protein delivery is a transformative tool for biologics research and medicine. Delivery into the cytosol allows proteins to diffuse throughout the cell and access subcellular organelles. Inefficient delivery caused by endosomal entrapment is often misidentified as cytosolic delivery. This inaccuracy muddles what should be a key checkpoint in assessing delivery efficiency. Green fluorescent protein (GFP) is a robust cargo small enough to passively diffuse from the cytosol into the nucleus. Fluorescence of GFP in the nucleus is a direct readout for cytosolic access and effective delivery. Here, we highlight recent examples from the literature for the accurate assessment of cytosolic protein delivery using GFP fluorescence in the cytosol and nucleus.

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Section: Introductionmentioning

confidence: 99%

Protein Delivery: If Your GFP (or Other Small Protein) Is in the Cytosol, It Will Also Be in the Nucleus

et al. 2021

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“…Arginine can reduce aggregation of proteins to stabilize the proteins' structure 96 . The surfactant is also generally used to stabilize proteins through reducing molecular interactions in different interfaces, such as polysorbate 97 . Chemical instability of PPs involves in product development, manufacturing and even post-administration.…”

Section: The Barriers To the Oral Absorption Of Ppsmentioning

confidence: 99%

Oral delivery of proteins and peptides: Challenges, status quo and future perspectives

Zhu

Chen

Paul

et al. 2021

Acta Pharmaceutica Sinica B

133

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Proteins and peptides (PPs) have gradually become more attractive therapeutic molecules than small molecular drugs due to their high selectivity and efficacy, but fewer side effects. Owing to the poor stability and limited permeability through gastrointestinal (GI) tract and epithelia, the therapeutic PPs are usually administered by parenteral route. Given the big demand for oral administration in clinical use, a variety of researches focused on developing new technologies to overcome GI barriers of PPs, such as enteric coating, enzyme inhibitors, permeation enhancers, nanoparticles, as well as intestinal microdevices. Some new technologies have been developed under clinical trials and even on the market. This review summarizes the history, the physiological barriers and the overcoming approaches, current clinical and preclinical technologies, and future prospects of oral delivery of PPs.

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“…In this section, only a few examples are given to highlight the potential of different kinds of CDSs for this purpose. Most of the information on this topic comes from pre-clinical studies, but a number of CDSs have been developed that are in various stages of clinical testing or are available commercially, which have been reviewed by other authors [129,130]. For instance, these authors reported that liposomes have been used to encapsulate insulin, anticancer peptides, and virus antigens, but not all of these applications were for oral delivery.…”

Section: Applicationsmentioning

confidence: 99%

Recent Advances in Encapsulation, Protection, and Oral Delivery of Bioactive Proteins and Peptides using Colloidal Systems

Perry

McClements

2020

Molecules

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There are many areas in medicine and industry where it would be advantageous to orally deliver bioactive proteins and peptides (BPPs), including ACE inhibitors, antimicrobials, antioxidants, hormones, enzymes, and vaccines. A major challenge in this area is that many BPPs degrade during storage of the product or during passage through the human gut, thereby losing their activity. Moreover, many BPPs have undesirable taste profiles (such as bitterness or astringency), which makes them unpleasant to consume. These challenges can often be overcome by encapsulating them within colloidal particles that protect them from any adverse conditions in their environment, but then release them at the desired site-of-action, which may be inside the gut or body. This article begins with a discussion of BPP characteristics and the hurdles involved in their delivery. It then highlights the characteristics of colloidal particles that can be manipulated to create effective BPP-delivery systems, including particle composition, size, and interfacial properties. The factors impacting the functional performance of colloidal delivery systems are then highlighted, including their loading capacity, encapsulation efficiency, protective properties, retention/release properties, and stability. Different kinds of colloidal delivery systems suitable for encapsulation of BPPs are then reviewed, such as microemulsions, emulsions, solid lipid particles, liposomes, and microgels. Finally, some examples of the use of colloidal delivery systems for delivery of specific BPPs are given, including hormones, enzymes, vaccines, antimicrobials, and ACE inhibitors. An emphasis is on the development of food-grade colloidal delivery systems, which could be used in functional or medical food applications. The knowledge presented should facilitate the design of more effective vehicles for the oral delivery of bioactive proteins and peptides.

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Protein drug delivery: current dosage form profile and formulation strategies

Cited by 30 publications

References 131 publications

Protein Delivery: If Your GFP (or Other Small Protein) Is in the Cytosol, It Will Also Be in the Nucleus

Protein Delivery: If Your GFP (or Other Small Protein) Is in the Cytosol, It Will Also Be in the Nucleus

Oral delivery of proteins and peptides: Challenges, status quo and future perspectives

Recent Advances in Encapsulation, Protection, and Oral Delivery of Bioactive Proteins and Peptides using Colloidal Systems

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