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Protein-Based Biomaterial for Pharmaceutical and Biomedical Applications

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A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: closed (30 August 2021) | Viewed by 24259

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Special Issue Editors

Dr. Kazuaki Taguchi

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Guest Editor

Faculty of Pharmacy, Keio University, Tokyo, Japan
Interests: blood transport proteins; drug delivery; liposome; micelle

Dr. Victor Tuan Giam Chuang

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Guest Editor

Curtin Medical School, Faculty of Health Sciences, Curtin University, Kent Street, Bentley, Perth, WA 6102, Australia
Interests: albumin; liposome; drug delivery; enhanced permeability retention effect; protein; functionalization of plasma proteins for pharmaceutical applications
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Biological proteins are essential intra- and extracellular components for maintaining homeostasis in a wide variety of living organisms, and some of them have vital physiological activities. Several bioactive protein products, such as enzymes, coagulation factors, and hormonal preparations, have been developed and used in modern medical care contributing to human health and welfare. In addition, biological proteins such as albumin and immunoglobulin (antibody) have been used as biomaterials to solve clinical problems by taking advantage of their inherent structure and unique functions. Focusing on the potentials of these biological proteins in the field of medicine and pharmacy, many phenomenal attempts have been made to develop novel and innovative protein-based products for the treatment of a variety of disorders worldwide. This Special Issue of Pharmaceuticals on “Protein-Based Biomaterial for Pharmaceutical and Biomedical Applications” will include both original articles and reviews focused on protein- and biotechnology-based products/materials aimed for use in medicine, pharmaceutical, imaging, and diagnostic applications. In particular, manuscripts containing the findings and knowledge of biological proteins as clinically viable medicinal materials and cutting-edge scientific technology to make biomedical materials are also welcome.

Dr. Kazuaki Taguchi
Dr. Victor Tuan Giam Chuang
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Protein
Drug delivery
Targeting
Pharmacotherapy
Imaging
Diagnostic

Published Papers (7 papers)

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Research

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15 pages, 3667 KiB

Open AccessEditor’s ChoiceArticle

Human Hair Keratin Composite Scaffold: Characterisation and Biocompatibility Study on NIH 3T3 Fibroblast Cells

by Jamal Moideen Muthu Mohamed, Ali Alqahtani, Adel Al Fatease, Taha Alqahtani, Barkat Ali Khan, B. Ashmitha and R. Vijaya

Pharmaceuticals 2021, 14(8), 781; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14080781 - 09 Aug 2021

Cited by 23 | Viewed by 4232

Abstract

The aim of this study was to transform human hair keratin waste into a scaffold for soft tissue engineering to heal wounds. The keratin was extracted using the Shindai method. Keratin and polyvinyl alcohol (PVA) was cross-linked with alginate dialdehyde and converted into a scaffold by the freeze-drying method using gentamycin sulphate (GS) as a model drug. The scaffold was subjected to Fourier transform infrared spectra (FTIR), swelling index, porosity, water absorption, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), X-ray diffraction (XRD), drug release, and cell viability (MTT) analysis. The scaffold was tested for keratinocyte growth using the murine fibroblast cell line (NIH 3T3 cells). The outcome from the keratin had a molecular weight band between 52–38 kDa in SDS-PAGE (Sodium dodecylsulfate-Polyacrylamide gel electrophoresis). A porous scaffold was capable of water absorption (73.64 ± 14.29%), swelling ability (68.93 ± 1.33%), and the release of GS shown as 97.45 ± 4.57 and 93.86 ± 5.22 of 1:4 and 1:3 scaffolds at 16 h. The physicochemical evaluation revealed that the prepared scaffold exhibits the proper structural integrity: partially crystalline with a strong thermal property. The scaffold demonstrated better cell viability against the murine fibroblast cell line (NIH 3T3 cells). In conclusion, we found that the prepared composite scaffold (1:4) can be used for wound healing applications. Full article

(This article belongs to the Special Issue Protein-Based Biomaterial for Pharmaceutical and Biomedical Applications)

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15 pages, 2455 KiB

Open AccessArticle

Apamin-Conjugated Alendronate Sodium Nanocomplex for Management of Pancreatic Cancer

by Nabil A. Alhakamy, Osama A. A. Ahmed, Usama A. Fahmy and Shadab Md

Pharmaceuticals 2021, 14(8), 729; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14080729 - 27 Jul 2021

Cited by 17 | Viewed by 2388

Abstract

Pancreatic cancer has a low survival rate and has limited therapeutic options due to the peculiarity of the tumor tissue. Cancer nanotechnology provides several opportunities to resolve such difficulties as a result of the high surface-to-volume ratio of nanostructures. Peptide-drug nanocomplexes have proved to have immense potential in anticancer activity against pancreatic cancer cells. Thus, in the present study apamin (APA) and alendronate sodium (ALS) were combined to form nanocomplexes (APA-ALS-NC) against pancreatic cancer cells. Optimization of ALS, incubation time, and sonication time in terms of particle size of the nanocomplex was carried out. The optimized formulation was evaluated for anticancer activities in pancreatic cancer cells (PANC-1 cells). A Box-Behnken design using ALS, incubation time, and sonication time as independent factors and particle size as the response was chosen to optimize the APA-ALS-NC formulation. The optimized APA-ALS-NC had a particle size of 161.52 ± 8.4 nm. The evaluation of APA-ALS-NC in PANC-1 cells was carried out using various in vitro tests. The IC₅₀ values were determined by MTT assay and found to be 37.6 ± 1.65, 13.4 ± 0.59, and 1.01 ± 0.04 µg/mL for ALS, APA, and APA-ALS-NC, respectively. The higher cytotoxicity activity of APA-ALS-NC was confirmed from the higher percentage of cells in the necrosis phase (apoptosis study) and the G2-M phase (cell cycle study) compared to that of ALS and APA. While the loss of mitochondrial membrane potential was less for APA-ALS-NC, the levels of IL-1β, TNF-α, caspase-3, ROS, IL-6, and NF-kB showed that APA-ALS-NC can significantly enhance apoptosis and cytotoxicity in PANC-1 cells. Moreover, Bax (10.87 ± 1.36), Bcl-2 (0.27 ± 0.02), and p53 (9.16 ± 1.22) gene expressions confirmed that APA-ALS-NC had a significant apoptotic effect compared to ALS and APA. In summary, the APA-ALS-NC had a more significant cytotoxic effect than ALS and APA. The results of the present study are promising for further evaluation in pre-clinical and clinical trials for arriving at a successful therapeutic strategy against pancreatic cancer. Full article

(This article belongs to the Special Issue Protein-Based Biomaterial for Pharmaceutical and Biomedical Applications)

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20 pages, 4153 KiB

Open AccessArticle

Albumin Nanoparticle Formulation for Heart-Targeted Drug Delivery: In Vivo Assessment of Congestive Heart Failure

by Nikita Lomis, Ziyab K. Sarfaraz, Aiman Alruwaih, Susan Westfall, Dominique Shum-Tim and Satya Prakash

Pharmaceuticals 2021, 14(7), 697; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14070697 - 19 Jul 2021

Cited by 7 | Viewed by 3069

Abstract

Congestive heart failure is a fatal cardiovascular disease resulting in tissue necrosis and loss of cardiac contractile function. Inotropic drugs such as milrinone are commonly used to improve the myocardial contractility and heart function. However, milrinone is associated with severe side effects and lower circulation time. In this article, a novel protein nanoparticle formulation for heart-targeted delivery of milrinone has been designed and tested. The formulation was prepared using albumin protein conjugated with the targeting ligand, angiotensin II peptide to form nanoparticles following the ethanol desolvation method. The formulation was characterized for size, charge, and morphology and tested in a rat model of congestive heart failure to study pharmacokinetics, biodistribution, and efficacy. The overall cardiac output parameters were evaluated comparing the formulation with the control non-targeted drug, milrinone lactate. This formulation exhibited improved pharmacokinetics with a mean retention time of 123.7 min, half-life of 101.3 min, and clearance rate of 0.24 L/(kg*h). The targeted formulation also significantly improved ejection fraction and fractional shortening parameters thus improving cardiac function. This study demonstrates a new approach in delivering inotropic drugs such as milrinone for superior treatment of congestive heart failure. Full article

(This article belongs to the Special Issue Protein-Based Biomaterial for Pharmaceutical and Biomedical Applications)

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15 pages, 2687 KiB

Open AccessArticle

Polymerized Albumin Receptor of Hepatitis B Virus for Evading the Reticuloendothelial System

by Kurumi Takagi, Masaharu Somiya, Joohee Jung, Masumi Iijima and Shun’ichi Kuroda

Pharmaceuticals 2021, 14(5), 408; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14050408 - 25 Apr 2021

Cited by 2 | Viewed by 2663

Abstract

Various strategies, such as optimization of surface chemistry, size, shape, and charge, have been undertaken to develop nanoparticles (NPs) as DDS (drug delivery system) nanocarriers for evading the reticuloendothelial system (RES) in vivo. We previously developed a hollow NP composed of hepatitis B virus (HBV) surface antigen L proteins and lipid bilayers, hereinafter referred to as bio-nanocapsule (BNC), as a nonviral DDS nanocarrier. Such a BNC harbors the HBV-derived human hepatic cell-specific infection mechanism, and intravenously injected BNCs by themselves were shown to avoid clearance by RES-rich organs and accumulate in target tissues. In this study, since the surface modification with albumins is known to prolong the circulation time of nanomedicines, we examined whether the polymerized albumin receptor (PAR) of BNCs contributes to RES evasion in mouse liver. Our results show that NPs conjugated with peptides possessing sufficient PAR activity were captured by Kupffer cells less efficiently in vitro and were able to circulate for a longer period of time in vivo. Comparing with polyethylene glycol, PAR peptides were shown to reduce the recognition by RES to equal content. Taken together, our results strongly suggest that the PAR domain of BNCs, as well as HBV, harbors an innate RES evasion mechanism. Therefore, the surface modification with PAR peptides could be an alternative strategy for improving the pharmacodynamics and pharmacokinetics of forthcoming nanomedicines. Full article

(This article belongs to the Special Issue Protein-Based Biomaterial for Pharmaceutical and Biomedical Applications)

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12 pages, 1876 KiB

Open AccessArticle

Synthesis and In Vitro Assessment of pH-Sensitive Human Serum Albumin Conjugates of Pirarubicin

by Kenji Tsukigawa, Shuhei Imoto, Keishi Yamasaki, Koji Nishi, Toshihiko Tsutsumi, Shoko Yokoyama, Yu Ishima and Masaki Otagiri

Pharmaceuticals 2021, 14(1), 22; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14010022 - 30 Dec 2020

Cited by 3 | Viewed by 2567

Abstract

In a previous study, we reported on the development of a synthetic polymer conjugate of pirarubicin (THP) that was formed via an acid-labile hydrazone bond between the polymer and the THP. However, the synthetic polymer itself was non-biodegradable, which could lead to unexpected adverse effects. Human serum albumin (HSA), which has a high biocompatibility and good biodegradability, is also a potent carrier for delivering antitumor drugs. The objective of this study was to develop pH-sensitive HSA conjugates of THP (HSA-THP), and investigate the release of THP and the cytotoxicity under acidic conditions in vitro for further clinical development. HSA-THP was synthesized by conjugating maleimide hydrazone derivatives of THP with poly-thiolated HSA using 2-iminothiolane, via a thiol-maleimide coupling reaction. We synthesized two types of HSA-THP that contained different amounts of THP (HSA-THP2 and HSA-THP4). Free THP was released from both of the HSA conjugates more rapidly at an acidic pH, and the rates of release for HSA-THP2 and HSA-THP4 were similar. Moreover, both HSA-THPs exhibited a higher cytotoxicity at acidic pH than at neutral pH, which is consistent with the effective liberation of free THP under acidic conditions. These findings suggest that these types of HSA-THPs are promising candidates for further development. Full article

(This article belongs to the Special Issue Protein-Based Biomaterial for Pharmaceutical and Biomedical Applications)

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13 pages, 2975 KiB

Open AccessArticle

In Vitro and Ex Vivo Evaluation of Penetratin as a Non-invasive Permeation Enhancer in the Penetration of Salmon Calcitonin through TR146 Buccal Cells and Porcine Buccal Tissues

by Taekwang Keum, Gyubin Noh, Jo-Eun Seo, Santosh Bashyal and Sangkil Lee

Pharmaceuticals 2020, 13(11), 408; https://0-doi-org.brum.beds.ac.uk/10.3390/ph13110408 - 21 Nov 2020

Cited by 10 | Viewed by 2330

Abstract

Buccal tissues are considered one of the potential alternative delivery route because of fast drug absorption and onset of action due to high vascularization and a non-keratinized epithelial membrane. In this study, the effect of Penetratin on the permeation of salmon calcitonin (sCT), a model macromolecular peptide drug, through TR146 buccal cells and porcine buccal tissues has been evaluated. To observe permeation profile of sCT, TR146 buccal cells were treated with Alexa 647 conjugated sCT (Alexa 647-sCT) with different concentrations of fluorescein isothiocyanate -labeled Penetratin (FITC-Penetratin) ranging from 0 to 40 μM, and analyzed using flow cytometry and confocal laser scanning microscopy. Intracellular penetration of FITC-Penetratin rapidly increased at low concentrations from 0 to 15 μM and it gradually increased at concentrations above 15 μM. Intracellular penetration of Alexa 647-sCT enhanced with the increase of FITC-Penetratin concentration. When TR146 cell layers and buccal tissues were co-treated with sCT and Penetratin as permeation enhancer, the flux of sCT increased as per Penetratin concentration. Compared to the control, 12.2 μM of Penetratin enhanced the flux of sCT in TR146 cell layers and buccal tissues by 5.5-fold and 93.7-fold, respectively. These results strongly suggest that Penetratin may successfully act as a non-invasive permeation enhancer for macromolecular peptide drug delivery through buccal routes. Full article

(This article belongs to the Special Issue Protein-Based Biomaterial for Pharmaceutical and Biomedical Applications)

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Review

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17 pages, 2271 KiB

Open AccessFeature PaperReview

When Albumin Meets Liposomes: A Feasible Drug Carrier for Biomedical Applications

by Kazuaki Taguchi, Yuko Okamoto, Kazuaki Matsumoto, Masaki Otagiri and Victor Tuan Giam Chuang

Pharmaceuticals 2021, 14(4), 296; https://0-doi-org.brum.beds.ac.uk/10.3390/ph14040296 - 26 Mar 2021

Cited by 25 | Viewed by 5633

Abstract

Albumin, the most abundant protein in plasma, possesses some inherent beneficial structural and physiological characteristics that make it suitable for use as a drug delivery agent, such as an extraordinary drug-binding capacity and long blood retention, with a high biocompatibility. The use of these characteristics as a nanoparticle drug delivery system (DDS) offers several advantages, including a longer circulation time, lower toxicity, and more significant drug loading. To date, many innovative liposome preparations have been developed in which albumin is involved as a DDS. These novel albumin-containing liposome preparations show superior deliverability for genes, hydrophilic/hydrophobic substances and proteins/peptides to the targeting area compared to original liposomes by virtue of their high biocompatibility, stability, effective loading content, and the capacity for targeting. This review summarizes the current status of albumin applications in liposome-based DDS, focusing on albumin-coated liposomes and albumin-encapsulated liposomes as a DDS carrier for potential medical applications. Full article

(This article belongs to the Special Issue Protein-Based Biomaterial for Pharmaceutical and Biomedical Applications)

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