Special Issue "Polymer Nanoparticles for Delivery of Therapeutic Proteins"

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 28 February 2022.

Special Issue Editor

Dr. Pedro Fonte
E-Mail Website1 Website2
Guest Editor
1. Centre for Marine Sciences (CCMAR), Faculty of Sciences and Technology, University of Algarve, Faro, Portugal
2. iBB - Institute for Bioengineering and Biosciences, Department of Bioengineering, Instituto Superior Técnico, University of Lisbon, Lisbon, Portugal
Interests: drug delivery; nanomedicine; protein delivery; protein characterization; freeze-drying; biopharmaceutical; tissue engineering; wound healing; biomaterials; translational medicine
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Special Issue Information

Dear Colleagues,

Therapeutic proteins have been attracting great attention in drug development, due to thei importance in treating severe health problems and diseases, such as cancer, genetic disorders, exposure to infectious agents, and autoimmune or inflammatory conditions. They are advantageous over conventional drugs, mainly due to their superior bioactivity and specificity, which improves the therapy outcome and decreases the probability of possible side-effects. However, the delivery of therapeutic proteins is challenging because they are prone to suffer instability caused by external factors like harsh pH, enzymatic degradation, and others, hampering their bioactivity and half-life in the body. Further, the uptake of therapeutic proteins through biological barriers is very challenging, due to their high molecular weight.

The encapsulation of therapeutic proteins into nanoparticles comes to the front line as a strategy to overcome the problems associated with therapeutic protein delivery. Among the different encapsulating materials found in the literature, polymers both from natural and synthetic sources are some of the most important ones due to their versatility, biocompatibility, biodegradability, and ability to tailor the production of nanoparticles. Polymer nanoparticles are optimal materials for therapeutic protein delivery because they can protect the structure of the loaded protein, to deliver it in a sustained, controlled or targeted manner, and to promote the uptake of proteins through biological barriers. Furthermore, the combination of polymer nanoparticles with other encapsulating materials and excipients such as protease inhibitors and permeation enhancers have been demonstrated to be a good strategy, to enhance the bioavailability of therapeutic proteins and improve the treatment of several diseases.

Overall, this Special Issue aims to provide an overview of the recent advances on the delivery of therapeutic proteins using polymer nanoparticles, focusing on promising strategies that allow improving therapies and patients’ quality of life.

As Guest Editor, I cordially invite all researchers to contribute in the form of original research articles or reviews in this important and exciting research field.

Dr. Pedro Fonte
Guest Editor

Manuscript Submission Information

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Keywords

  • polymer nanoparticle
  • drug delivery
  • biopharmaceutical
  • therapeutic protein
  • protein delivery
  • nanomedicine
  • protease inhibitor
  • permeation enhancer
  • polymer-protein interaction
  • biomaterials

Published Papers (4 papers)

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Research

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Article
ELISA- and Activity Assay-Based Quantification of BMP-2 Released In Vitro Can Be Biased by Solubility in “Physiological” Buffers and an Interfering Effect of Chitosan
Pharmaceutics 2021, 13(4), 582; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13040582 - 19 Apr 2021
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Abstract
Chitosan nanogel-coated polycaprolactone (PCL) fiber mat-based implant prototypes with tailored release of bone morphogenic protein 2 (BMP-2) are a promising approach to achieve implant-mediated bone regeneration. In order to ensure reliable in vitro release results, the robustness of a commercially available ELISA for [...] Read more.
Chitosan nanogel-coated polycaprolactone (PCL) fiber mat-based implant prototypes with tailored release of bone morphogenic protein 2 (BMP-2) are a promising approach to achieve implant-mediated bone regeneration. In order to ensure reliable in vitro release results, the robustness of a commercially available ELISA for E. coli-derived BMP-2 and the parallel determination of BMP-2 recovery using a quantitative biological activity assay were investigated within a common release setup, with special reference to solubility and matrix effects. Without bovine serum albumin and Tween 20 as solubilizing additives to release media buffed at physiological pH, BMP-2 recoveries after release were notably reduced. In contrast, the addition of chitosan to release samples caused an excessive recovery. A possible explanation for these effects is the reversible aggregation tendency of BMP-2, which might be influenced by an interaction with chitosan. The interfering effects highlighted in this study are of great importance for bio-assay-based BMP-2 quantification, especially in the context of pharmaceutical release experiments. Full article
(This article belongs to the Special Issue Polymer Nanoparticles for Delivery of Therapeutic Proteins)
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Article
Uptake of Polyelectrolyte Functionalized Upconversion Nanoparticles by Tau-Aggregated Neuron Cells
Pharmaceutics 2021, 13(1), 102; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13010102 - 14 Jan 2021
Cited by 1 | Viewed by 842
Abstract
Tauopathy is the aggregation phenomenon of tau proteins and associated with neurodegenerative diseases. It metastasizes via the transfer of tau aggregates to adjacent neuron cells; however, the mechanism has not yet been fully understood. Moreover, if the materials used for designing drug delivery [...] Read more.
Tauopathy is the aggregation phenomenon of tau proteins and associated with neurodegenerative diseases. It metastasizes via the transfer of tau aggregates to adjacent neuron cells; however, the mechanism has not yet been fully understood. Moreover, if the materials used for designing drug delivery system to treat such neurodegenerative diseases do not undergo biodegradation or exocytosis but remains in cells or tissues, they raise concerns about their possible negative impacts. In this study, the uptake and delivery mechanisms of nano-sized carriers in tau aggregated neuron cells were investigated employing polyelectrolyte-functionalized upconversion nanoparticles (UCNPs) of diameter ~100 nm. Investigation through bioimaging was carried out by irradiating the particles with near-infrared light. Here, forskolin and okadaic acid were employed to induce tau aggregation into healthy neuron cells. It was noticed that the tau-aggregated neuron cells, when treated with relatively large sized UCNPs, showed uptake efficiency similar to that of normal neuron cells however their intracellular transport and exocytosis were impacted, and most of the carriers remained accumulated around lysosome. This demonstrates that metastasis mechanisms of tauopathy can get influenced by the size of carriers and are to be considered during their pharmacokinetic studies which is often not addressed in many drug delivery studies. Full article
(This article belongs to the Special Issue Polymer Nanoparticles for Delivery of Therapeutic Proteins)
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Article
Nanoparticles Based on Quaternary Ammonium Chitosan-methyl-β-cyclodextrin Conjugate for the Neuropeptide Dalargin Delivery to the Central Nervous System: An In Vitro Study
Pharmaceutics 2021, 13(1), 5; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13010005 - 22 Dec 2020
Cited by 2 | Viewed by 876
Abstract
Peptide oral administration is a hard goal to reach, especially if the brain is the target site. The purpose of the present study was to set up a vehicle apt to promote oral absorption of the neuropeptide dalargin (DAL), allowing it to cross [...] Read more.
Peptide oral administration is a hard goal to reach, especially if the brain is the target site. The purpose of the present study was to set up a vehicle apt to promote oral absorption of the neuropeptide dalargin (DAL), allowing it to cross the intestinal mucosal barrier, resist enzymatic degradation, and transport drugs to the brain after crossing the blood–brain barrier. Therefore, a chitosan quaternary ammonium derivative was synthesized and conjugated with methyl-β-cyclodextrin to prepare DAL-medicated nanoparticles (DAL-NP). DAL-NP particle size was 227.7 nm, zeta potential +8.60 mV, encapsulation efficiency 89%. DAL-NP protected DAL from degradation by chymotrypsin or pancreatin and tripled DAL degradation time compared to non-encapsulated DAL. Use of DAL-NP was safe for either Caco-2 or bEnd.3 cells, with the latter selected as a blood–brain barrier model. DAL-NP could also cross either the Caco-2 or bEnd.3 monolayer by the transepithelial route. The results suggest a potential DAL-NP ability to transport to the brain a DAL dose fraction administered orally, although in vivo experiments will be needed to confirm the present data obtained in vitro. Full article
(This article belongs to the Special Issue Polymer Nanoparticles for Delivery of Therapeutic Proteins)
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Review

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Review
An Overview on Spray-Drying of Protein-Loaded Polymeric Nanoparticles for Dry Powder Inhalation
Pharmaceutics 2020, 12(11), 1032; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12111032 - 29 Oct 2020
Viewed by 816
Abstract
The delivery of therapeutic proteins remains a challenge, despite recent technological advances. While the delivery of proteins to the lungs is the gold standard for topical and systemic therapy through the lungs, the issue still exists. While pulmonary delivery is highly attractive due [...] Read more.
The delivery of therapeutic proteins remains a challenge, despite recent technological advances. While the delivery of proteins to the lungs is the gold standard for topical and systemic therapy through the lungs, the issue still exists. While pulmonary delivery is highly attractive due to its non-invasive nature, large surface area, possibility of topical and systemic administration, and rapid absorption circumventing the first-pass effect, the absorption of therapeutic proteins is still ineffective, largely due to the immunological and physicochemical barriers of the lungs. Most studies using spray-drying for the nanoencapsulation of drugs focus on the delivery of conventional drugs, which are less susceptible to bioactivity loss, compared to proteins. Herein, the development of polymeric nanoparticles by spray-drying for the delivery of therapeutic proteins is reviewed with an emphasis on its advantages and challenges, and the techniques to evaluate their in vitro and in vivo performance. The protein stability within the carrier and the features of the carrier are properly addressed. Full article
(This article belongs to the Special Issue Polymer Nanoparticles for Delivery of Therapeutic Proteins)
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