Recent Advancement in Biotechnology and Drug Development Using Cutting-Edge Platforms

Topic Information

Dear Colleagues,

This Topic encompasses recent drug, gene and cellular discoveries that aim to revolutionise current ways of delivering effective, personalized and challenging medical therapies. This covers new drugs or the repurposing of old ones, as well as gene therapies, whether edited via CRISPR technology or based on native genes, that induce specialized cellular differentiation and functionalization. The Issue will also cover novel stem-based delivery platforms and ways to target-deliver molecules and genes in complex biological systems. The Issue also aims to explore future potential endeavours and futuristic prospectives on the direction of new inventions in treating uncurable diseases ranging from metabolic symptoms such as diabetes, into more prominent health challenges such as hearing and vision imprairment as well as age-related disorders such as Alzheimer’s Disease and general decline of cognitive functions.

Dr. Hani Al-Salami
Dr. Armin Mooranian
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
BioMed biomed	-	-	2021	21.9 Days	CHF 1000
Biomedicines biomedicines	3.9	5.2	2013	14.6 Days	CHF 2600
Osteology osteology	-	-	2021	30.9 Days	CHF 1000
Pharmaceuticals pharmaceuticals	4.3	6.1	2004	13.9 Days	CHF 2900
Pharmaceutics pharmaceutics	4.9	7.9	2009	15.5 Days	CHF 2900

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Published Papers (7 papers)

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15 pages, 2894 KiB  

Open AccessPerspective

Perspectives on CRISPR Genome Editing to Prevent Prion Diseases in High-Risk Individuals

by Milan M. Medd and Qi Cao

Biomedicines 2024, 12(8), 1725; https://doi.org/10.3390/biomedicines12081725 - 1 Aug 2024

Viewed by 3076

Abstract

Prion diseases are neurodegenerative disorders caused by misfolded prion proteins. Although rare, the said diseases are always fatal; they commonly cause death within months of developing clinical symptoms, and their diagnosis is exceptionally difficult pre-mortem. There are no known cures or treatments other [...] Read more.

Prion diseases are neurodegenerative disorders caused by misfolded prion proteins. Although rare, the said diseases are always fatal; they commonly cause death within months of developing clinical symptoms, and their diagnosis is exceptionally difficult pre-mortem. There are no known cures or treatments other than symptomatic care. Given the aggressiveness of prion diseases on onset, therapies after disease onset could be challenging. Prevention to reduce the incidence or to delay the disease onset has been suggested to be a more feasible approach. In this perspective article, we summarize our current understandings of the origin, risk factors, and clinical manifestations of prion diseases. We propose a PCR testing of the blood to identify PRNP gene polymorphisms at codons 129 and 127 in individuals with familial PRNP mutations to assess the risk. We further present the CRISPR/Cas9 gene editing strategy as a perspective preventative approach for these high-risk individuals to induce a polymorphic change at codon 127 of the PRNP gene, granting immunity to prion diseases in selected high-risk individuals, in particular, in individuals with familial PRNP mutations. Full article

(This article belongs to the Topic Recent Advancement in Biotechnology and Drug Development Using Cutting-Edge Platforms)

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15 pages, 5552 KiB  

Open AccessArticle

Synthesis, Computational Study, and In Vitro α-Glucosidase Inhibitory Action of 1,3,4-Thiadiazole Derivatives of 3-Aminopyridin-2(1H)-ones

by Zarina Shulgau, Irina V. Palamarchuk, Shynggys Sergazy, Assel Urazbayeva, Yerlan Ramankulov and Ivan V. Kulakov

Pharmaceuticals 2024, 17(3), 377; https://doi.org/10.3390/ph17030377 - 15 Mar 2024

Cited by 3 | Viewed by 1827

Abstract

This article reports on the synthesis of nine promising new 1,3,4-thiadiazole derivatives based on 3-aminopyridones, containing various acidic linkers. The synthesis was carried out by cyclizing the corresponding thiohydrazides 4a–c and anhydrides of glutaric, maleic, and phthalic acids upon heating in [...] Read more.

This article reports on the synthesis of nine promising new 1,3,4-thiadiazole derivatives based on 3-aminopyridones, containing various acidic linkers. The synthesis was carried out by cyclizing the corresponding thiohydrazides 4a–c and anhydrides of glutaric, maleic, and phthalic acids upon heating in acetic acid solution. The conducted bio-screening of the synthesized new 1,3,4-thiadiazole derivatives containing different acidic linkers (butanoic, acrylic, and benzoic acids) showed that they have significant inhibitory activity against α-glucosidase (up to 95.0%), which is 1.9 times higher than the value for the reference drug acarbose (49.5%). Moreover, one of the 1,3,4-thiadiazole derivatives with a benzoic acid linker—2-(5-((6-Methyl-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridin-3-yl)carbamoyl)-1,3,4-thiadiazol-2-yl)benzoic acid (9′b)—showed an IC₅₀ value of 3.66 mM, nearly 3.7 times lower than that of acarbose (IC₅₀ = 13.88 mM). High inhibitory activity was also shown by 1,3,4-thiadiazole derivatives with a butanoic acid linker (compounds 7b, 7c)—with IC₅₀ values of 6.70 and 8.42 mM, respectively. A correlation between the structure of the compounds and their activity was also established. The results of molecular docking correlated well with the bioanalytical data. In particular, the presence of a butanoic acid linker and a benzoic fragment in compounds 7b, 7c, and 9b increased their binding affinity with selected target proteins compared to other derivatives 3–6 (a–c). Calculations according to Lipinski’s rule of five also showed that the synthesized compounds 7b, 7c, and 9b fully comply with Ro5 and meet all criteria for good permeability and acceptable oral bioavailability of potential drugs. These positive bioanalytical results will stimulate further in-depth studies, including in vivo models. Full article

(This article belongs to the Topic Recent Advancement in Biotechnology and Drug Development Using Cutting-Edge Platforms)

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19 pages, 2779 KiB  

Open AccessArticle

Green Synthesis of Cocos nucifera-Based Nanomaterials and Mechanistic Basis of Their Antimicrobial Action

by Zuriatou Yajeh Tanka, Naphtali Odogu Ankoro, Vincent Ngouana, Franklin Loïc Tchinda Taghu, Abongta Lum Mforbesi, Branly-Natalien Nguena-Dongue, Julius Nsami Ndi, Boniface Pone Kamdem, Paul Keilah Lunga and Fabrice Fekam Boyom

BioMed 2024, 4(1), 59-77; https://doi.org/10.3390/biomed4010005 - 6 Mar 2024

Viewed by 2503

Abstract

Caused by pathogenic microorganisms, infectious diseases are known to cause high mortality rates, severe burdens of disability, and serious worldwide aftermaths. Drug-resistant pathogens have reduced the efficacy of available therapies against these diseases, thus accentuating the need to search for effective antimicrobials. Medicinal [...] Read more.

Caused by pathogenic microorganisms, infectious diseases are known to cause high mortality rates, severe burdens of disability, and serious worldwide aftermaths. Drug-resistant pathogens have reduced the efficacy of available therapies against these diseases, thus accentuating the need to search for effective antimicrobials. Medicinal plants have served as starting material for the preparation of a number of antimicrobial agents. To this end, the present study highlights the green synthesis of Cocos nucifera-based nanomaterials and evaluation of the mechanistic basis of their antimicrobial action. Accordingly, Cocos nucifera extract was used for the reduction of silver nitrate solution to afford silver nanoparticles. These entities were further incorporated onto sulfuric-acid-based activated carbons to generate the nanocomposites. The antimicrobial activity of the as-prepared nanomaterials was evaluated using the broth microdilution method, while the antioxidant activity was assessed through standard methods. The cytotoxicity of potent nanomaterials was assessed on Vero cells by the spectrophotometric method. As a result, nanoparticles were successfully synthesized, as evidenced by the ultraviolet–visible spectroscopy analysis that revealed an intense absorption spectrum at 433 nm. Fourier Transform Infrared Spectroscopy presented the functional group moieties involved as a capping and reducing agent in the synthesis of the nanomaterials. The incubation of nanomaterials with selected bacterial and fungal strains has led to significant inhibitory effects of these pathogens with minimum inhibitory concentrations ranging from 7.813 to 250 μg/mL. In antioxidant assays, the nanocomposites presented scavenging activities comparable to those of ascorbic acid. Cytotoxicity experiment revealed no toxic effects on Vero cells (range of selectivity indices: from >4 to >128). These results provide evidence of the implication of Cocos nucifera-based nanomaterials in targeting bacterial or fungal systems that mediate free-radical damage or by inhibiting the oxidative damage caused by selected bacteria and fungi, the most susceptible being Escherichia coli and Candida albicans, respectively. Full article

(This article belongs to the Topic Recent Advancement in Biotechnology and Drug Development Using Cutting-Edge Platforms)

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19 pages, 3042 KiB  

Open AccessReview

Upstream and Downstream Bioprocessing in Enzyme Technology

by Nadia Guajardo and Rodrigo A. Schrebler

Pharmaceutics 2024, 16(1), 38; https://doi.org/10.3390/pharmaceutics16010038 - 27 Dec 2023

Cited by 5 | Viewed by 7813

Abstract

The development of biotransformation must integrate upstream and downstream processes. Upstream bioprocessing will influence downstream bioprocessing. It is essential to consider this because downstream processes can constitute the highest cost in bioprocessing. This review comprehensively overviews the most critical aspects of upstream and [...] Read more.

The development of biotransformation must integrate upstream and downstream processes. Upstream bioprocessing will influence downstream bioprocessing. It is essential to consider this because downstream processes can constitute the highest cost in bioprocessing. This review comprehensively overviews the most critical aspects of upstream and downstream bioprocessing in enzymatic biocatalysis. The main upstream processes discussed are enzyme production, enzyme immobilization methodologies, solvent selection, and statistical optimization methodologies. The main downstream processes reviewed in this work are biocatalyst recovery and product separation and purification. The correct selection and combination of upstream and downstream methodologies will allow the development of a sustainable and highly productive system. Full article

(This article belongs to the Topic Recent Advancement in Biotechnology and Drug Development Using Cutting-Edge Platforms)

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19 pages, 3899 KiB  

Open AccessEditor’s ChoiceArticle

Long-Term Survival and Induction of Operational Tolerance to Murine Islet Allografts by Co-Transplanting Cyclosporine A Microparticles and CTLA4-Ig

by Purushothaman Kuppan, Jordan Wong, Sandra Kelly, Jiaxin Lin, Jessica Worton, Chelsea Castro, Joy Paramor, Karen Seeberger, Nerea Cuesta-Gomez, Colin C. Anderson, Gregory S. Korbutt and Andrew R. Pepper

Pharmaceutics 2023, 15(9), 2201; https://doi.org/10.3390/pharmaceutics15092201 - 25 Aug 2023

Cited by 2 | Viewed by 1957

Abstract

One strategy to prevent islet rejection is to create a favorable immune-protective local environment at the transplant site. Herein, we utilize localized cyclosporine A (CsA) delivery to islet grafts via poly(lactic-co-glycolic acid) (PLGA) microparticles to attenuate allograft rejection. CsA-eluting PLGA microparticles were prepared [...] Read more.

One strategy to prevent islet rejection is to create a favorable immune-protective local environment at the transplant site. Herein, we utilize localized cyclosporine A (CsA) delivery to islet grafts via poly(lactic-co-glycolic acid) (PLGA) microparticles to attenuate allograft rejection. CsA-eluting PLGA microparticles were prepared using a single emulsion (oil-in-water) solvent evaporation technique. CsA microparticles alone significantly delayed islet allograft rejection compared to islets alone (p < 0.05). Over 50% (6/11) of recipients receiving CsA microparticles and short-term cytotoxic T lymphocyte-associated antigen 4-Ig (CTLA4-Ig) therapy displayed prolonged allograft survival for 214 days, compared to 25% (2/8) receiving CTLA4-Ig alone. CsA microparticles alone and CsA microparticles + CTLA4-Ig islet allografts exhibited reduced T-cell (CD4⁺ and CD8⁺ cells, p < 0.001) and macrophage (CD68⁺ cells, p < 0.001) infiltration compared to islets alone. We observed the reduced mRNA expression of proinflammatory cytokines (IL-6, IL-10, INF-γ, and TNF-α; p < 0.05) and chemokines (CCL2, CCL5, CCL22, and CXCL10; p < 0.05) in CsA microparticles + CTLA4-Ig allografts compared to islets alone. Long-term islet allografts contained insulin⁺ and intra-graft FoxP3⁺ T regulatory cells. The rapid rejection of third-party skin grafts (C3H) in islet allograft recipients suggests that CsA microparticles + CTLA4-Ig therapy induced operational tolerance. This study demonstrates that localized CsA drug delivery plus short-course systemic immunosuppression promotes an immune protective transplant niche for allogeneic islets. Full article

(This article belongs to the Topic Recent Advancement in Biotechnology and Drug Development Using Cutting-Edge Platforms)

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28 pages, 2277 KiB  

Open AccessEditor’s ChoiceReview

Nanosystems in Cardiovascular Medicine: Advancements, Applications, and Future Perspectives

by Hossein Omidian, Niloofar Babanejad and Luigi X. Cubeddu

Pharmaceutics 2023, 15(7), 1935; https://doi.org/10.3390/pharmaceutics15071935 - 12 Jul 2023

Cited by 23 | Viewed by 4107

Abstract

Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality globally. Despite significant advancements in the development of pharmacological therapies, the challenges of targeted drug delivery to the cardiovascular system persist. Innovative drug-delivery systems have been developed to address these challenges and [...] Read more.

Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality globally. Despite significant advancements in the development of pharmacological therapies, the challenges of targeted drug delivery to the cardiovascular system persist. Innovative drug-delivery systems have been developed to address these challenges and improve therapeutic outcomes in CVDs. This comprehensive review examines various drug delivery strategies and their efficacy in addressing CVDs. Polymeric nanoparticles, liposomes, microparticles, and dendrimers are among the drug-delivery systems investigated in preclinical and clinical studies. Specific strategies for targeted drug delivery, such as magnetic nanoparticles and porous stent surfaces, are also discussed. This review highlights the potential of innovative drug-delivery systems as effective strategies for the treatment of CVDs. Full article

(This article belongs to the Topic Recent Advancement in Biotechnology and Drug Development Using Cutting-Edge Platforms)

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11 pages, 1886 KiB  

Open AccessArticle

Chronological Analysis of First-in-Class Drugs Approved from 2011 to 2022: Their Technological Trend and Origin

by Ryo Okuyama

Pharmaceutics 2023, 15(7), 1794; https://doi.org/10.3390/pharmaceutics15071794 - 22 Jun 2023

Cited by 8 | Viewed by 3413

Abstract

The discovery and development of first-in-class (FIC) drugs are becoming increasingly important due to increasing reimbursement pressure and personalized medication. To investigate the technological trends and origin of FIC drugs, the FIC drugs approved in the U.S. from January 2011 to December 2022 [...] Read more.

The discovery and development of first-in-class (FIC) drugs are becoming increasingly important due to increasing reimbursement pressure and personalized medication. To investigate the technological trends and origin of FIC drugs, the FIC drugs approved in the U.S. from January 2011 to December 2022 were analyzed. The analysis shows that previous major target families, viz. enzymes, G-protein coupled receptors, transporters, and transcription factors, are no longer considered major in recent years. Instead, the shares of secreted proteins/peptides and mRNAs have continuously increased from 2011–2014 to 2019–2022, suggesting that the target family of FIC drugs has shifted to molecules previously considered challenging as drug targets. Small molecules were predominant in 2011–2014, followed by a large increase in antibody medicines in 2015–2018 and further diversification of antibody medicine modalities in 2019–2022. Nucleic acid medicine has also continuously increased its share, suggesting that diversifying modalities supports the creation of FIC drugs toward challenging target molecules. Over half of FIC drugs were created by small and medium enterprises (SMEs), especially young companies established in the 1990s and 2000s. All SMEs that produced more than one FIC drug approved in 2019–2022 have the strong technological capability in a specific modality. Investment in modality technologies and facilitating mechanisms to translate academic modality technologies to start-ups might be important for enhancing FIC drug development. Full article

(This article belongs to the Topic Recent Advancement in Biotechnology and Drug Development Using Cutting-Edge Platforms)

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