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1.
IET Nanobiotechnol ; 16(3): 85-91, 2022 May.
Article in English | MEDLINE | ID: covidwho-1758388

ABSTRACT

Mesoporous magnetic nanoparticles of haematite were synthesised using plant extracts according to bioethics principles. The structural, physical and chemical properties of mesoporous Fe2 O3 nanoparticles synthesised with the green chemistry approach were evaluated by XRD, SEM, EDAX, BET, VSM and HRTEM analysis. Then, their toxicity against normal HUVECs and MCF7 cancer cells was evaluated by MTT assay for 48 h. These biogenic mesoporous magnetic nanoparticles have over 71% of doxorubicin loading efficiency, resulting in a 50% reduction of cancer cells at a 0.5 µg.ml-1 concentration. Therefore, it is suggested that mesoporous magnetic nanoparticles be used as a multifunctional agent in medicine (therapeutic-diagnostic). The produced mesoporous magnetic nanoparticles with its inherent structural properties such as polygonal structure (increasing surface area to particle volume) and porosity with large pore volume became a suitable substrate for loading the anti-cancer drug doxorubicin.


Subject(s)
Nanoparticles , Silicon Dioxide , Doxorubicin/chemistry , Doxorubicin/pharmacology , Drug Carriers/chemistry , Drug Delivery Systems/methods , Drug Liberation , Humans , Nanoparticles/chemistry , Porosity , Silicon Dioxide/chemistry
2.
Int J Mol Sci ; 23(4)2022 Feb 21.
Article in English | MEDLINE | ID: covidwho-1705083

ABSTRACT

We theoretically investigated the adsorption of two common anti-COVID drugs, favipiravir and chloroquine, on fluorinated C60 fullerene, decorated with metal ions Cr3+, Fe2+, Fe3+, Ni2+. We focused on the effect of fluoridation on the interaction of fullerene with metal ions and drugs in an aqueous solution. We considered three model systems, C60, C60F2 and C60F48, and represented pristine, low-fluorinated and high-fluorinated fullerenes, respectively. Adsorption energies, deformation of fullerene and drug molecules, frontier molecular orbitals and vibrational spectra were investigated in detail. We found that different drugs and different ions interacted differently with fluorinated fullerenes. Cr3+ and Fe2+ ions lead to the defluorination of low-fluorinated fullerenes. Favipiravir also leads to their defluorination with the formation of HF molecules. Therefore, fluorinated fullerenes are not suitable for the delivery of favipiravir and similar drugs molecules. In contrast, we found that fluorine enhances the adsorption of Ni2+ and Fe3+ ions on fullerene and their activity to chloroquine. Ni2+-decorated fluorinated fullerenes were found to be stable and suitable carriers for the loading of chloroquine. Clear shifts of infrared, ultraviolet and visible spectra can provide control over the loading of chloroquine on Ni2+-doped fluorinated fullerenes.


Subject(s)
Amides/chemistry , Antiviral Agents/chemistry , Chloroquine/chemistry , Fullerenes/chemistry , Metals/chemistry , Pyrazines/chemistry , COVID-19 , Density Functional Theory , Drug Carriers/chemistry , Drug Delivery Systems , Halogenation , Models, Molecular , Nickel/chemistry
3.
Int J Mol Sci ; 23(3)2022 Jan 19.
Article in English | MEDLINE | ID: covidwho-1625612

ABSTRACT

Repurposing of the anthelminthic drug niclosamide was proposed as an effective treatment for inflammatory airway diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease. Niclosamide may also be effective for the treatment of viral respiratory infections, such as SARS-CoV-2, respiratory syncytial virus, and influenza. While systemic application of niclosamide may lead to unwanted side effects, local administration via aerosol may circumvent these problems, particularly when the drug is encapsulated into small polyethylene glycol (PEG) hydrospheres. In the present study, we examined whether PEG-encapsulated niclosamide inhibits the production of mucus and affects the pro-inflammatory mediator CLCA1 in mouse airways in vivo, while effects on mucociliary clearance were assessed in excised mouse tracheas. The potential of encapsulated niclosamide to inhibit TMEM16A whole-cell Cl- currents and intracellular Ca2+ signalling was assessed in airway epithelial cells in vitro. We achieved encapsulation of niclosamide in PEG-microspheres and PEG-nanospheres (Niclo-spheres). When applied to asthmatic mice via intratracheal instillation, Niclo-spheres strongly attenuated overproduction of mucus, inhibited secretion of the major proinflammatory mediator CLCA1, and improved mucociliary clearance in tracheas ex vivo. These effects were comparable for niclosamide encapsulated in PEG-nanospheres and PEG-microspheres. Niclo-spheres inhibited the Ca2+ activated Cl- channel TMEM16A and attenuated mucus production in CFBE and Calu-3 human airway epithelial cells. Both inhibitory effects were explained by a pronounced inhibition of intracellular Ca2+ signals. The data indicate that poorly dissolvable compounds such as niclosamide can be encapsulated in PEG-microspheres/nanospheres and deposited locally on the airway epithelium as encapsulated drugs, which may be advantageous over systemic application.


Subject(s)
Niclosamide/administration & dosage , Pneumonia/drug therapy , Respiratory System/drug effects , Animals , Asthma/drug therapy , Asthma/metabolism , Asthma/pathology , COVID-19/complications , COVID-19/drug therapy , Cells, Cultured , Disease Models, Animal , Drug Carriers/chemistry , Drug Compounding , Humans , Hydrogels/chemistry , Instillation, Drug , Mice , Microspheres , Mucus/drug effects , Mucus/metabolism , Nanospheres/administration & dosage , Nanospheres/chemistry , Niclosamide/chemistry , Niclosamide/pharmacokinetics , Pneumonia/pathology , Polyethylene Glycols/chemistry , Respiratory Mucosa/drug effects , Respiratory Mucosa/metabolism , Respiratory System/metabolism , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Trachea
4.
Adv Drug Deliv Rev ; 180: 114079, 2022 01.
Article in English | MEDLINE | ID: covidwho-1620432

ABSTRACT

Polyethylene glycol or PEG has a long history of use in medicine. Many conventional formulations utilize PEG as either an active ingredient or an excipient. PEG found its use in biotechnology therapeutics as a tool to slow down drug clearance and shield protein therapeutics from undesirable immunogenicity. Nanotechnology field applies PEG to create stealth drug carriers with prolonged circulation time and decreased recognition and clearance by the mononuclear phagocyte system (MPS). Most nanomedicines approved for clinical use and experimental nanotherapeutics contain PEG. Among the most recent successful examples are two mRNA-based COVID-19 vaccines that are delivered by PEGylated lipid nanoparticles. The breadth of PEG use in a wide variety of over the counter (OTC) medications as well as in drug products and vaccines stimulated research which uncovered that PEG is not as immunologically inert as it was initially expected. Herein, we review the current understanding of PEG's immunological properties and discuss them in the context of synthesis, biodistribution, safety, efficacy, and characterization of PEGylated nanomedicines. We also review the current knowledge about immunological compatibility of other polymers that are being actively investigated as PEG alternatives.


Subject(s)
Drug Carriers , Nanomedicine , Polyethylene Glycols/chemistry , Animals , COVID-19 Vaccines/chemistry , COVID-19 Vaccines/immunology , Drug Delivery Systems , Humans
5.
ACS Appl Bio Mater ; 4(12): 8110-8128, 2021 12 20.
Article in English | MEDLINE | ID: covidwho-1597218

ABSTRACT

The design of advanced nanobiomaterials to improve analytical accuracy and therapeutic efficacy has become an important prerequisite for the development of innovative nanomedicines. Recently, phospholipid nanobiomaterials including 2-methacryloyloxyethyl phosphorylcholine (MPC) have attracted great attention with remarkable characteristics such as resistance to nonspecific protein adsorption and cell adhesion for various biomedical applications. Despite many recent reports, there is a lack of comprehensive review on the phospholipid nanobiomaterials from synthesis to diagnostic and therapeutic applications. Here, we review the synthesis and characterization of phospholipid nanobiomaterials focusing on MPC polymers and highlight their attractive potentials for applications in micro/nanofabricated fluidic devices, biosensors, lab-on-a-chip, drug delivery systems (DDSs), COVID-19 potential usages for early diagnosis and even treatment, and artificial extracellular matrix scaffolds for cellular engineering.


Subject(s)
Biocompatible Materials/chemistry , Drug Carriers/chemistry , Lab-On-A-Chip Devices , Nanostructures/chemistry , Phospholipids/chemistry , Biosensing Techniques/instrumentation , Biosensing Techniques/methods , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Humans , Microscopy, Confocal , SARS-CoV-2/isolation & purification
6.
Int J Nanomedicine ; 16: 8141-8158, 2021.
Article in English | MEDLINE | ID: covidwho-1581579

ABSTRACT

Chitosan has been investigated in several biological fields, including drug and gene delivery, tissue engineering antiviral and immunological adjuvant methods. It's a cationic copolymer of N-acetyl glucosamine and D-glucosamine with different molecular chain lengths, compositions, and sequences than N-acetyl glucosamine and D-glucosamine. It is biocompatible and cyto-compatible, as well as recyclable and bioresorbable. As effective drug delivery methods, chitosan nanoparticles are shaped into several pathways. The purpose of this article is to provide an overview of its antiviral application as a nanocarrier for antiviral medications, highlighting the benefits, limitations, and downsides. In this review, we will report the most recent COVID-19 vaccination advances. It will also be discussed what the future holds for chitosan nanoparticles in the treatment of coronaviruses.


Subject(s)
COVID-19 , Chitosan , Nanoparticles , Antiviral Agents , COVID-19/drug therapy , COVID-19 Vaccines , Drug Carriers , Drug Delivery Systems , Humans , SARS-CoV-2
7.
Molecules ; 27(1)2021 Dec 28.
Article in English | MEDLINE | ID: covidwho-1580565

ABSTRACT

Baricitinib (BTB) is an orally administered Janus kinase inhibitor, therapeutically used for the treatment of rheumatoid arthritis. Recently it has also been approved for the treatment of COVID-19 infection. In this study, four different BTB-loaded lipids (stearin)-polymer (Poly(d,l-lactide-co-glycolide)) hybrid nanoparticles (B-PLN1 to B-PLN4) were prepared by the single-step nanoprecipitation method. Next, they were characterised in terms of physicochemical properties such as particle size, zeta potential (ζP), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Based on preliminary evaluation, the B-PLN4 was regarded as the optimised formulation with particle size (272 ± 7.6 nm), PDI (0.225), ζP (-36.5 ± 3.1 mV), %EE (71.6 ± 1.5%) and %DL (2.87 ± 0.42%). This formulation (B-PLN4) was further assessed concerning morphology, in vitro release, and in vivo pharmacokinetic studies in rats. The in vitro release profile exhibited a sustained release pattern well-fitted by the Korsmeyer-Peppas kinetic model (R2 = 0.879). The in vivo pharmacokinetic data showed an enhancement (2.92 times more) in bioavailability in comparison to the normal suspension of pure BTB. These data concluded that the formulated lipid-polymer hybrid nanoparticles could be a promising drug delivery option to enhance the bioavailability of BTB. Overall, this study provides a scientific basis for future studies on the entrapment efficiency of lipid-polymer hybrid systems as promising carriers for overcoming pharmacokinetic limitations.


Subject(s)
Azetidines/pharmacokinetics , Drug Carriers/chemistry , Drug Liberation , Liposomes/chemistry , Nanoparticles/chemistry , Polymers/chemistry , Purines/pharmacokinetics , Pyrazoles/pharmacokinetics , Sulfonamides/pharmacokinetics , Administration, Oral , Animals , Azetidines/administration & dosage , Azetidines/chemistry , Biological Availability , Male , Purines/administration & dosage , Purines/chemistry , Pyrazoles/administration & dosage , Pyrazoles/chemistry , Rats , Rats, Wistar , Sulfonamides/administration & dosage , Sulfonamides/chemistry
8.
Molecules ; 26(24)2021 Dec 15.
Article in English | MEDLINE | ID: covidwho-1572568

ABSTRACT

The encapsulation mode of dexamethasone (Dex) into the cavity of ß-cyclodextrin (ß-CD), as well as its potential as an inhibitor of the COVID-19 main protease, were investigated using density functional theory with the recent dispersion corrections D4 and molecular docking calculations. Independent gradient model and natural bond orbital approaches allowed for the characterization of the host-guest interactions in the studied systems. Structural and energetic computation results revealed that hydrogen bonds and van der Waals interactions played significant roles in the stabilization of the formed Dex@ß-CD complex. The complexation energy significantly decreased from -179.50 kJ/mol in the gas phase to -74.14 kJ/mol in the aqueous phase. A molecular docking study was performed to investigate the inhibitory activity of dexamethasone against the COVID-19 target protein (PDB ID: 6LU7). The dexamethasone showed potential therapeutic activity as a SARS CoV-2 main protease inhibitor due to its strong binding to the active sites of the protein target, with predicted free energy of binding values of -29.97 and -32.19 kJ/mol as calculated from AutoDock4 and AutoDock Vina, respectively. This study was intended to explore the potential use of the Dex@ß-CD complex in drug delivery to enhance dexamethasone dissolution, thus improving its bioavailability and reducing its side effects.


Subject(s)
COVID-19/drug therapy , Dexamethasone/pharmacology , Protease Inhibitors/pharmacology , SARS-CoV-2/drug effects , beta-Cyclodextrins/pharmacology , Antiviral Agents/pharmacology , Drug Carriers/pharmacology , Humans , Molecular Docking Simulation
9.
Biomed Pharmacother ; 145: 112385, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1565522

ABSTRACT

Chemically modified mRNA represents a unique, efficient, and straightforward approach to produce a class of biopharmaceutical agents. It has been already approved as a vaccination-based method for targeting SARS-CoV-2 virus. The COVID-19 pandemic has highlighted the prospect of synthetic modified mRNA to efficiently and safely combat various diseases. Recently, various optimization advances have been adopted to overcome the limitations associated with conventional gene therapeutics leading to wide-ranging applications in different disease conditions. This review sheds light on emerging directions of chemically modified mRNAs to prevent and treat widespread chronic diseases, including metabolic disorders, cancer vaccination and immunotherapy, musculoskeletal disorders, respiratory conditions, cardiovascular diseases, and liver diseases.


Subject(s)
COVID-19/prevention & control , Chronic Disease/prevention & control , Chronic Disease/therapy , Genetic Therapy/methods , Immunotherapy/methods , Pandemics/prevention & control , RNA, Messenger/chemistry , SARS-CoV-2/immunology , Vaccines, Synthetic , Biological Availability , Drug Carriers , Forecasting , Gene Transfer Techniques , Genetic Vectors/administration & dosage , Genetic Vectors/therapeutic use , Humans , Immunotherapy, Active , RNA Stability , RNA, Messenger/administration & dosage , RNA, Messenger/immunology , RNA, Messenger/therapeutic use , SARS-CoV-2/genetics , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/immunology , /immunology
10.
Int J Mol Sci ; 22(23)2021 Nov 25.
Article in English | MEDLINE | ID: covidwho-1559503

ABSTRACT

Cancer is one of the most important health problems of our population, and one of the common anticancer treatments is chemotherapy. The disadvantages of chemotherapy are related to the drug's toxic effects, which act on cancer cells and the healthy part of the body. The solution of the problem is drug encapsulation and drug targeting. The present study aimed to develop a novel method of preparing multifunctional 5-Fluorouracil (5-FU) nanocarriers and their in vitro characterization. 5-FU polyaminoacid-based core@shell nanocarriers were formed by encapsulation drug-loaded nanocores with polyaminoacids multilayer shell via layer-by-layer method. The size of prepared nanocarriers ranged between 80-200 nm. Biocompatibility of our nanocarriers as well as activity of the encapsulated drug were confirmed by MTT tests. Moreover, the ability to the real-time observation of developed nanocarriers and drug accumulation inside the target was confirmed by fluorine magnetic resonance imaging (19F-MRI).


Subject(s)
Amino Acids/chemistry , Drug Carriers/administration & dosage , Drug Carriers/chemical synthesis , Fluorouracil/pharmacology , Mammary Neoplasms, Experimental/drug therapy , Nanoparticles/administration & dosage , Animals , Antimetabolites, Antineoplastic/chemistry , Antimetabolites, Antineoplastic/pharmacology , Female , Fluorouracil/chemistry , Mammary Neoplasms, Experimental/pathology , Nanoparticles/chemistry , Tumor Cells, Cultured
11.
Chem Pharm Bull (Tokyo) ; 69(12): 1141-1159, 2021.
Article in English | MEDLINE | ID: covidwho-1546823

ABSTRACT

Considerable efforts have been made on the development of lipid nanoparticles (LNPs) for delivering of nucleic acids in LNP-based medicines, including a first-ever short interfering RNA (siRNA) medicine, Onpattro, and the mRNA vaccines against the coronavirus disease 2019 (COVID-19), which have been approved and are currently in use worldwide. The successful rational design of ionizable cationic lipids was a major breakthrough that dramatically increased delivery efficiency in this field. The LNPs would be expected to be useful as a platform technology for the delivery of various therapeutic modalities for genome editing and even for undiscovered therapeutic mechanisms. In this review, the current progress of my research, including the molecular design of pH-sensitive cationic lipids, their applications for various tissues and cell types, and for delivering various macromolecules, including siRNA, antisense oligonucleotide, mRNA, and the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) system will be described. Mechanistic studies regarding relationships between the physicochemical properties of LNPs, drug delivery, and biosafety are also summarized. Furthermore, current issues that need to be addressed for next generation drug delivery systems are discussed.


Subject(s)
Drug Carriers/chemistry , Lipids/chemistry , Liposomes/chemistry , Nanoparticles/chemistry , COVID-19/immunology , COVID-19/prevention & control , COVID-19/virology , Cations/chemistry , Hydrogen-Ion Concentration , RNA, Guide/chemistry , RNA, Guide/metabolism , RNA, Small Interfering/chemistry , RNA, Small Interfering/metabolism , SARS-CoV-2/isolation & purification , /metabolism
12.
J Am Chem Soc ; 143(49): 20529-20545, 2021 12 15.
Article in English | MEDLINE | ID: covidwho-1541126

ABSTRACT

Unquestionably, polymers have influenced the world over the past 100 years. They are now more crucial than ever since the COVID-19 pandemic outbreak. The pandemic paved the way for certain polymers to be in the spotlight, namely sequence-defined polymers such as messenger ribonucleic acid (mRNA), which was the first type of vaccine to be authorized in the U.S. and Europe to protect against the SARS-CoV-2 virus. This rise of mRNA will probably influence scientific research concerning nucleic acids in general and RNA therapeutics in specific. In this Perspective, we highlight the recent trends in sequence-controlled and sequence-defined polymers. Then we discuss mRNA vaccines as an example to illustrate the need of ultimate sequence control to achieve complex functions such as specific activation of the immune system. We briefly present how mRNA vaccines are produced, the importance of modified nucleotides, the characteristic features, and the advantages and challenges associated with this class of vaccines. Finally, we discuss the chances and opportunities for polymer chemistry to provide solutions and contribute to the future progress of RNA-based therapeutics. We highlight two particular roles of polymers in this context. One represents conjugation of polymers to nucleic acids to form biohybrids. The other is concerned with advanced polymer-based carrier systems for nucleic acids. We believe that polymers can help to address present problems of RNA-based therapeutic technologies and impact the field beyond the COVID-19 pandemic.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 Vaccines/chemistry , COVID-19/drug therapy , Polymers/pharmacology , SARS-CoV-2/drug effects , /chemistry , Animals , Drug Carriers , Humans
13.
Acc Chem Res ; 54(23): 4283-4293, 2021 12 07.
Article in English | MEDLINE | ID: covidwho-1521679

ABSTRACT

After decades of extensive fundamental studies and clinical trials, lipid nanoparticles (LNPs) have demonstrated effective mRNA delivery such as the Moderna and Pfizer-BioNTech vaccines fighting against COVID-19. Moreover, researchers and clinicians have been investigating mRNA therapeutics for a variety of therapeutic indications including protein replacement therapy, genome editing, and cancer immunotherapy. To realize these therapeutics in the clinic, there are many formidable challenges. First, novel delivery systems such as LNPs with high delivery efficiency and low toxicity need to be developed for different cell types. Second, mRNA molecules need to be engineered for improved pharmaceutical properties. Lastly, the LNP-mRNA nanoparticle formulations need to match their therapeutic applications.In this Account, we summarize our recent advances in the design and development of various classes of lipids and lipid derivatives, which can be formulated with multiple types of mRNA molecules to treat diverse diseases. For example, we conceived a series of ionizable lipid-like molecules based on the structures of a benzene core, an amide linker, and hydrophobic tails. We identified N1,N3,N5-tris(3-(didodecylamino)propyl)benzene-1,3,5-tricarboxamide (TT3) as a lead compound for mRNA delivery both in vitro and in vivo. Moreover, we tuned the biodegradability of these lipid-like molecules by introducing branched ester or linear ester chains. Meanwhile, inspired by biomimetic compounds, we synthesized vitamin-derived lipids, chemotherapeutic conjugated lipids, phospholipids, and glycolipids. These scaffolds greatly broaden the chemical space of ionizable lipids for mRNA delivery. In another section, we highlight our efforts on the research direction of mRNA engineering. We previously optimized mRNA chemistry using chemically-modified nucleotides to increase the protein expression, such as pseudouridine (ψ), 5-methoxyuridine (5moU), and N1-methylpseudouridine (me1ψ). Also, we engineered the sequences of mRNA 5' untranslated regions (5'-UTRs) and 3' untranslated regions (3'-UTRs), which dramatically enhanced protein expression. With the progress of LNP development and mRNA engineering, we consolidate these technologies and apply them to treat diseases such as genetic disorders, infectious diseases, and cancers. For instance, TT3 and its analog-derived lipid-like nanoparticles can effectively deliver factor IX or VIII mRNA and recover the clotting activity in hemophilia mouse models. Engineered mRNAs encoding SARS-CoV-2 antigens serve well as vaccine candidates against COVID-19. Vitamin-derived lipid nanoparticles loaded with antimicrobial peptide-cathepsin B mRNA enable adoptive macrophage transfer to treat multidrug resistant bacterial sepsis. Biomimetic lipids such as phospholipids formulated with mRNAs encoding costimulatory receptors lead to enhanced cancer immunotherapy.Overall, lipid-mRNA nanoparticle formulations have considerably benefited public health in the COVID-19 pandemic. To expand their applications in clinical use, research work from many disciplines such as chemistry, engineering, materials, pharmaceutical sciences, and medicine need to be integrated. With these collaborative efforts, we believe that more and more lipid-mRNA nanoparticle formulations will enter the clinic in the near future and benefit human health.


Subject(s)
Drug Carriers/chemistry , Liposomes/chemistry , Nanoparticles/chemistry , RNA, Messenger/chemistry , Animals , Benzamides/chemistry , Biomimetic Materials/chemistry , Communicable Diseases/immunology , Communicable Diseases/therapy , Disease Models, Animal , Genetic Diseases, Inborn/immunology , Genetic Diseases, Inborn/therapy , Humans , Mice , Neoplasms/immunology , Neoplasms/therapy , Phospholipids/chemistry , RNA, Messenger/metabolism , RNA, Messenger/therapeutic use , Untranslated Regions , Vitamins/chemistry
14.
Chem Biol Interact ; 351: 109706, 2022 Jan 05.
Article in English | MEDLINE | ID: covidwho-1464614

ABSTRACT

The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.


Subject(s)
Drug Carriers/chemistry , Lung/metabolism , Peptides/administration & dosage , Proteins/administration & dosage , Administration, Inhalation , Animals , Drug Carriers/administration & dosage , Humans , Lung/drug effects , Lung Diseases/drug therapy , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Peptides/therapeutic use , Proteins/therapeutic use
15.
Mater Sci Eng C Mater Biol Appl ; 116: 111260, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1452344

ABSTRACT

Polymeric nanoparticulate systems allow the encapsulation of bio-active substances, giving them protection against external agents and increasing the drug's bioavailability. The use of biocompatible and biodegradable polymers usually guarantees the harmless character of the formulation, and a controlled drug release is also assured. A relatively easy procedure to obtain polymeric formulations of bioactive agents is ionotropic gelation, which allows the synthesis of chitosan (CS) - sodium tri-polyphosphate nanoparticles (NPs) loading encapsulated proteins. In this work, Bovine serum albumin (BSA) model protein and a recombinant porcine alpha interferon variant were used to obtain nanoparticulate formulations. The internalization of the encapsulated material by cells was studied using a BSA-fluorescein system; the fluorescent conjugate was observable inside the cells after 20 h of incubation. The therapeutic CS-alpha interferon formulation showed a maximum of protein released in vitro at around 90 h. This system was found to be safe in a cytotoxicity assay, while biological activity experiments in vitro showed antiviral protection of cells in the presence of encapsulated porcine alpha interferon. In vivo experiments in pigs revealed a significant and sustained antiviral response through overexpression of the antiviral markers OAS2 and PKR. This proves the preservation of porcine alpha interferon biological activity, and also that a lasting response was obtained. This procedure is an effective and safe method to formulate drugs in nanoparticulate systems, representing a significant contribution to the search for more effective drug delivery strategies.


Subject(s)
Chitosan , Nanoparticles , Pharmaceutical Preparations , Animals , Antiviral Agents/pharmacology , Biological Availability , Cattle , Drug Carriers , Drug Delivery Systems , Interferon-alpha , Particle Size , Polymers , Swine
16.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1186: 123015, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1487818

ABSTRACT

The potential of lipid nanoparticles (LNPs) as nucleic acid delivery vehicles has been demonstrated in recent years, culminating in the emergency use approval of LNP-based mRNA SARS-CoV-2 vaccines in late 2020. The determination of RNA content relative to LNP size can be important to the understanding of efficacy and adverse effects. This work presents the first description of a facile and rapid analytical method for online, size-dependent RNA payload distribution measurement using data from multi-angle light scattering, ultraviolet and refractive index detectors following separation of the LNPs by size-exclusion chromatography. The analysis was validated by size-based fractionation of the LNPs with subsequent offline analysis of the fractions. Four LNPs formulated with different PEG-lipids and different lipid compositions were tested. Good agreement was observed between the online and offline size-based RNA distributions among all four LNPs, demonstrating the utility of the online method for LNP-encapsulated RNA in general, and suggesting a means for simplified biophysical quantitation of a dosing-related critical quality attribute.


Subject(s)
COVID-19 Vaccines/chemistry , Chromatography, Gel/methods , Drug Carriers/chemistry , Nanoparticles/chemistry , RNA, Messenger/chemistry , RNA, Viral/chemistry , SARS-CoV-2/genetics , COVID-19/virology , COVID-19 Vaccines/immunology , Drug Delivery Systems , Humans , Lipids/chemistry , Particle Size , RNA, Messenger/immunology , RNA, Viral/immunology , SARS-CoV-2/chemistry , SARS-CoV-2/immunology
17.
J Nanobiotechnology ; 19(1): 305, 2021 Oct 06.
Article in English | MEDLINE | ID: covidwho-1455975

ABSTRACT

Molecular imprinting (MI) is a technique that creates a template of a molecule for improving complementary binding sites in terms of size and shape to a peptide, protein, bacteria, mammalian cell, or virus on soft materials (such as polymers, hydrogels, or self-assembled materials). MI has been widely investigated for over 90 years in various industries but is now focused on improved tissue engineering, regenerative medicine, drug delivery, sensors, diagnostics, therapeutics and other medical applications. Molecular targets that have been studied so far in MI include those for the major antigenic determinants of microorganisms (like bacteria or viruses) leading to innovations in disease diagnosis via solid-phase extraction separation and biomimetic sensors. As such, although not widely investigated yet, MI demonstrates much promise for improving the detection of and treatment for the current Coronavirus Disease of 2019 (COVID-2019) pandemic as well as future pandemics. In this manner, this review will introduce the numerous applications of MI polymers, particularly using proteins and peptides, and how these MI polymers can be used as improved diagnostic and therapeutic tools for COVID-19.


Subject(s)
COVID-19/diagnosis , Molecularly Imprinted Polymers/therapeutic use , SARS-CoV-2/isolation & purification , Antibodies , Drug Carriers , Humans , Molecular Imprinting , Molecularly Imprinted Polymers/chemistry , Peptides , Proteins , Receptors, Cell Surface
18.
Curr Top Med Chem ; 20(11): 915-962, 2020.
Article in English | MEDLINE | ID: covidwho-1453165

ABSTRACT

BACKGROUND: Emerging viral zoonotic diseases are one of the major obstacles to secure the "One Health" concept under the current scenario. Current prophylactic, diagnostic and therapeutic approaches often associated with certain limitations and thus proved to be insufficient for customizing rapid and efficient combating strategy against the highly transmissible pathogenic infectious agents leading to the disastrous socio-economic outcome. Moreover, most of the viral zoonoses originate from the wildlife and poor knowledge about the global virome database renders it difficult to predict future outbreaks. Thus, alternative management strategy in terms of improved prophylactic vaccines and their delivery systems; rapid and efficient diagnostics and effective targeted therapeutics are the need of the hour. METHODS: Structured literature search has been performed with specific keywords in bibliographic databases for the accumulation of information regarding current nanomedicine interventions along with standard books for basic virology inputs. RESULTS: Multi-arrayed applications of nanomedicine have proved to be an effective alternative in all the aspects regarding the prevention, diagnosis, and control of zoonotic viral diseases. The current review is focused to outline the applications of nanomaterials as anti-viral vaccines or vaccine/drug delivery systems, diagnostics and directly acting therapeutic agents in combating the important zoonotic viral diseases in the recent scenario along with their potential benefits, challenges and prospects to design successful control strategies. CONCLUSION: This review provides significant introspection towards the multi-arrayed applications of nanomedicine to combat several important zoonotic viral diseases.


Subject(s)
Drug Delivery Systems/methods , Viral Vaccines/chemistry , Viral Zoonoses/diagnosis , Viral Zoonoses/prevention & control , Viral Zoonoses/therapy , Viruses/drug effects , Animals , Animals, Wild , Biosensing Techniques , Drug Carriers/chemistry , Drug Compounding , Drug Liberation , Humans , Nanomedicine , Nanoparticles/chemistry , Polymers/chemistry , Polymers/metabolism , Transfection , Viruses/metabolism
19.
Carbohydr Polym ; 273: 118605, 2021 Dec 01.
Article in English | MEDLINE | ID: covidwho-1370153

ABSTRACT

Advanced biomaterials provide an interesting and versatile platform to implement new and more effective strategies to fight bacterial infections. Chitosan is one of these biopolymers and possesses relevant features for biomedical applications. Here we synthesized nanoparticles of chitosan derivatized with diethylaminoethyl groups (ChiDENPs) to emulate the choline residues in the pneumococcal cell wall and act as ligands for choline-binding proteins (CBPs). Firstly, we assessed the ability of diethylaminoethyl (DEAE) to sequester the CBPs present in the bacterial surface, thus promoting chain formation. Secondly, the CBP-binding ability of ChiDENPs was purposed to encapsulate a bio-active molecule, the antimicrobial enzyme Cpl-711 (ChiDENPs-711), with improved stability over non-derivatized chitosan. The enzyme-loaded system released more than 90% of the active enzybiotic in ≈ 2 h, above the usual in vivo half-life of this kind of enzymes. Therefore, ChiDENPs provide a promising platform for the controlled release of CBP-enzybiotics in biological contexts.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biomimetic Materials/chemistry , Chitosan/analogs & derivatives , Drug Carriers/chemistry , Endopeptidases/pharmacology , Nanoparticles/chemistry , A549 Cells , Anti-Bacterial Agents/chemistry , Bacterial Proteins/metabolism , Biomimetic Materials/metabolism , Chitosan/chemistry , Chitosan/metabolism , Drug Carriers/metabolism , Drug Liberation , Endopeptidases/chemistry , Humans , Nanoparticles/metabolism , Streptococcus pneumoniae/drug effects
20.
Biomed Pharmacother ; 144: 112260, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1446462

ABSTRACT

Abnormal structural and molecular changes in malignant tissues were thoroughly investigated and utilized to target tumor cells, hence rescuing normal healthy tissues and lowering the unwanted side effects as non-specific cytotoxicity. Various ligands for cancer cell specific markers have been uncovered and inspected for directional delivery of the anti-cancer drug to the tumor site, in addition to diagnostic applications. Over the past few decades research related to the ligand targeted therapy (LTT) increased tremendously aiming to treat various pathologies, mainly cancers with well exclusive markers. Malignant tumors are known to induce elevated levels of a variety of proteins and peptides known as cancer "markers" as certain antigens (e.g., Prostate specific membrane antigen "PSMA", carcinoembryonic antigen "CEA"), receptors (folate receptor, somatostatin receptor), integrins (Integrin αvß3) and cluster of differentiation molecules (CD13). The choice of an appropriate marker to be targeted and the design of effective ligand-drug conjugate all has to be carefully selected to generate the required therapeutic effect. Moreover, since some tumors express aberrantly high levels of more than one marker, some approaches investigated targeting cancer cells with more than one ligand (dual or multi targeting). We aim in this review to report an update on the cancer-specific receptors and the vehicles to deliver cytotoxic drugs, including recent advancements on nano delivery systems and their implementation in targeted cancer therapy. We will discuss the advantages and limitations facing this approach and possible solutions to mitigate these obstacles. To achieve the said aim a literature search in electronic data bases (PubMed and others) using keywords "Cancer specific receptors, cancer specific antibody, tumor specific peptide carriers, cancer overexpressed proteins, gold nanotechnology and gold nanoparticles in cancer treatment" was carried out.


Subject(s)
Antineoplastic Agents/administration & dosage , Cancer Vaccines/therapeutic use , Drug Carriers , Drug Resistance, Neoplasm , Genetic Therapy , Neoplasms/therapy , Precision Medicine , Animals , Antineoplastic Agents/metabolism , CRISPR-Cas Systems , Cancer Vaccines/adverse effects , Drug Compounding , Drug Resistance, Neoplasm/genetics , Humans , Molecular Targeted Therapy , Nanoparticles , Nanotechnology , Neoplasms/diagnosis , Neoplasms/genetics , Neoplasms/immunology
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