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1.
J Am Chem Soc ; 146(12): 8659-8667, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38407928

ABSTRACT

The solid-state synthesis of single-crystalline organic polymers, having functional properties, remains an attractive and developing research area in polymer chemistry and materials science. However, light-triggered topochemical synthesis of crystalline polymers comprising an organoboron backbone has not yet been reported. Here, we describe an intriguing example of single-crystal-to-single-crystal (SCSC) rapid photosynthesis (occurs on a seconds-scale) of two structurally different linear organoboron polymers, driven by environmentally sustainable visible/sun light, obtained from the same monomer molecule. A newly designed Lewis acid-base type molecular B ← N organoboron adduct (consisting of an organoboron core and naphthylvinylpyridine ligands) crystallizes in two solid-state forms featuring the same chemical structure but different 3D structural topologies, namely, monomers 1 and 2. The solvate molecule-free crystals of 1 undergo topochemical photopolymerization via an unusual olefin-naphthyl ring [2 + 2] cyclization to yield the single crystalline [3]-ladderane polymer 1P growing along the B ← N linkages, accompanied by instantaneous and violent macroscopic mechanical motions or photosalient effects (such as bending-reshaping and jumping motions). In contrast, visible light-harvesting single crystals of 2 quantitatively polymerize to a B ← N bond-stabilized polymer 2P in a SCSC fashion owing to the rapid [2 + 2] cycloaddition reaction among olefin double bonds. Such olefin bonds in the crystals of 2 are suitably preorganized for photoreaction due to the presence of solvate molecules in the crystal packing. Single crystals of 2 also show photodynamic jumping motions - in response to visible light but in a relatively slower fashion than the crystals of 1. In addition to SCSC topochemical polymerization and dynamic motions, both monomer crystals and their single-crystalline polymers feature green emissive and short-lived room-temperature phosphorescence properties upon excitation with visible-light wavelength.

2.
J Microencapsul ; : 1-22, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38967562

ABSTRACT

Osteoarthritis (OA), affecting around 240 million people globally is a major threat. Currently, available drugs only treat the symptoms of OA; they cannot reverse the disease's progression. The delivery of drugs to afflicted joints is challenging because of poor vasculature of articular cartilage results in their less bioavailability and quick elimination from the joints. Recently approved drugs such as KGN and IL-1 receptor antagonists also encounter challenges because of inadequate formulations. Therefore, microspheres could be a potential player for the intervention of OA owing to its excellent physicochemical properties. This review primarily focuses on microspheres of distinct biomaterials acting as cargo for drugs and biologicals via different delivery routes in the effective management of OA. Microspheres can improve the efficacy of therapeutics by targeting strategies at specific body locations. This review also highlights clinical trials conducted in the last few decades.

3.
AAPS PharmSciTech ; 25(3): 41, 2024 Feb 17.
Article in English | MEDLINE | ID: mdl-38366178

ABSTRACT

Viral infections represent a significant threat to global health due to their highly communicable and potentially lethal nature. Conventional antiviral interventions encounter challenges such as drug resistance, tolerability issues, specificity concerns, high costs, side effects, and the constant mutation of viral proteins. Consequently, the exploration of alternative approaches is imperative. Therefore, nanotechnology-embedded drugs excelled as a novel approach purporting severe life-threatening viral disease. Integrating nanomaterials and nanoparticles enables ensuring precise drug targeting, improved drug delivery, and fostered pharmacokinetic properties. Notably, nanocrystals (NCs) stand out as one of the most promising nanoformulations, offering remarkable characteristics in terms of physicochemical properties (higher drug loading, improved solubility, and drug retention), pharmacokinetics (enhanced bioavailability, dose reduction), and optical properties (light absorptivity, photoluminescence). These attributes make NCs effective in diagnosing and ameliorating viral infections. This review comprises the prevalence, pathophysiology, and resistance of viral infections along with emphasizing on failure of current antivirals in the management of the diseases. Moreover, the review also highlights the role of NCs in various viral infections in mitigating, diagnosing, and other NC-based strategies combating viral infections. In vitro, in vivo, and clinical studies evident for the effectiveness of NCs against viral pathogens are also discussed.


Subject(s)
Nanoparticles , Virus Diseases , Humans , Pharmaceutical Preparations/chemistry , Biological Availability , Drug Delivery Systems , Virus Diseases/drug therapy , Nanoparticles/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use
4.
AAPS PharmSciTech ; 25(6): 178, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095623

ABSTRACT

Dry powder inhalers (DPIs) are state-of-the-art pulmonary drug delivery systems. This article explores the transformative impact of nanotechnology on DPIs, emphasizing the Quality Target Product Profile (QTPP) with a focus on aerodynamic performance and particle characteristics. It navigates global regulatory frameworks, underscoring the need for safety and efficacy standards. Additionally, it highlights the emerging field of nanoparticulate dry powder inhalers, showcasing their potential to enhance targeted drug delivery in respiratory medicine. This concise overview is a valuable resource for researchers, physicians, and pharmaceutical developers, providing insights into the development and commercialization of advanced inhalation systems.


Subject(s)
Drug Delivery Systems , Dry Powder Inhalers , Dry Powder Inhalers/methods , Humans , Administration, Inhalation , Drug Delivery Systems/methods , Nanoparticles/chemistry , Lung/metabolism , Lung/drug effects , Nanomedicine/methods , Particle Size , Nanotechnology/methods
5.
AAPS PharmSciTech ; 25(6): 149, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38954224

ABSTRACT

Silibinin (SIL) Encapsulated Nanoliquid Crystalline (SIL-NLCs) particles were prepared to study neuroprotective effect against amyloid beta (Aß1-42) neurotoxicity in Balb/c mice model. Theses NLCs were prepared through hot emulsification and probe sonication technique. The pharmacodynamics was investigatigated on Aß1-42 intracerebroventricular (ICV) injected Balb/c mice. The particle size, zeta potential and drug loading were optimized to be 153 ± 2.5 nm, -21 mV, and 8.2%, respectively. Small angle X-ray (SAXS) and electron microscopy revealed to crystalline shape of SIL-NLCs. Thioflavin T (ThT) fluroscence and circular dichroism (CD) technique were employed to understand monomer inhibition effect of SIL-NLCs on Aß1-4. In neurobehavioral studies, SIL-NLCs exhibited enhanced mitigation of memory impairment induced on by Aß1-42 in T-maze and new object recognition test (NORT). Whereas biochemical and histopathological estimation of brain samples showed reduction in level of Aß1-42 aggregate, acetylcholine esterase (ACHE) and reactive oxygen species (ROS). SIL-NLCs treated animal group showed higher protection against Aß1-42 toxicity compared to free SIL and Donopezil (DPZ). Therefore SIL-NLCs promises great prospect in neurodegenerative diseases such as Alzheimer's disease.


Subject(s)
Amyloid beta-Peptides , Mice, Inbred BALB C , Neuroprotective Agents , Peptide Fragments , Silybin , Animals , Amyloid beta-Peptides/toxicity , Amyloid beta-Peptides/metabolism , Mice , Silybin/pharmacology , Silybin/administration & dosage , Peptide Fragments/toxicity , Neuroprotective Agents/pharmacology , Neuroprotective Agents/administration & dosage , Male , Brain/drug effects , Brain/metabolism , Brain/pathology , Particle Size , Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , Disease Models, Animal , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Acetylcholinesterase/metabolism
6.
Mol Pharm ; 20(9): 4714-4728, 2023 09 04.
Article in English | MEDLINE | ID: mdl-37523676

ABSTRACT

This work focuses on developing nanoemulsions using a low-energy emulsification method for the codelivery of donepezil and memantine in one dosage form intended to be administered via the intranasal route for enhanced brain delivery. The nanoemulsion formulation was prepared using a low emulsification technique and characterized using various microscopy and nasal ciliotoxicity studies. The safe nanoemulsion was intended for preclinical pharmacokinetics with brain distribution and pharmacodynamics in a scopolamine-induced murine model. The formulated nanoemulsion was 16 nm in size, with a zeta potential of -7.22 mV, and exhibited a spherical shape. The brain concentration of IN-administered NE for DPZ and MEM was ∼678 and 249 ng/mL after 15 min. This concentration is more than 2 times higher in amount when compared with NE administered via PO, free drug solution administered via IN and PO route both. However, the plasma concentration of IN-administered NE for DPZ and MEM was ∼3 and 28 ng/mL after 15 min. In pharmacodynamic studies, the efficacy of NE administered via the IN route was higher when compared with other groups in neurobehavioral, biochemical estimation, and gene expression studies. The results suggest that the IN route can be explored in the future for the delivery of actives via nanocolloidal carriers in the brain for neurological disorders and can serve as promising alternatives for conventional dosage forms and routes.


Subject(s)
Memantine , Nanoparticles , Mice , Animals , Donepezil , Administration, Intranasal , Brain/metabolism , Scopolamine , Emulsions/metabolism , Nanoparticles/chemistry , Particle Size
7.
Eur J Neurol ; 30(11): 3557-3567, 2023 Nov.
Article in English | MEDLINE | ID: mdl-36880679

ABSTRACT

The gut-brain axis augments the bidirectional communication between the gut and brain and modulates gut homeostasis and the central nervous system through the hypothalamic-pituitary-adrenal axis, enteroendocrine system, neuroendocrine system, inflammatory and immune pathways. Preclinical and clinical reports showed that gut dysbiosis might play a major regulatory role in neurological diseases such as epilepsy, Parkinson's, multiple sclerosis, and Alzheimer's disease. Epilepsy is a chronic neurological disease that causes recurrent and unprovoked seizures, and numerous risk factors are implicated in developing epilepsy. Advanced consideration of the gut-microbiota-brain axis can reduce ambiguity about epilepsy pathology, antiepileptic drugs, and effective therapeutic targets. Gut microbiota sequencing analysis reported that the level of Proteobacteria, Verrucomicrobia, Fusobacteria, and Firmicutes was increased and the level of Actinobacteria and Bacteroidetes was decreased in epilepsy patients. Clinical and preclinical studies also indicated that probiotics, ketogenic diet, faecal microbiota transplantation, and antibiotics can improve gut dysbiosis and alleviate seizure by enhancing the abundance of healthy biota. This study aims to give an overview of the connection between gut microbiota, and epilepsy, how gut microbiome changes may cause epilepsy, and whether gut microbiome restoration could be used as a treatment for epilepsy.

8.
Phys Chem Chem Phys ; 25(46): 32040-32050, 2023 Nov 29.
Article in English | MEDLINE | ID: mdl-37982166

ABSTRACT

Boron nitrides are very important and are used as lubricants, insulating agents, etc. Interactions of such systems with small molecules are important. This study examined the potential of B3N3 (triboron trinitride) to act as both an electron acceptor and an electron donor in the formation of noncovalent interactions. The anisotropic electronic distribution observed in the electrostatic potential map supported the B3N3's ability to exhibit the predicted electron donor-acceptor duality. Further computational investigations on optimized gas-phase complexes of B3N3:(NH3)n=1-3, B3N3:(NCH)n=1-6, B3N3:(N2H2)n=1-3 and (B3N3)2 confirmed that the B3N3 molecule can participate in B⋯N triel bonding interactions and H···N hydrogen bonding interactions. These energetically stable complexes are primarily governed by electrostatic and polarization interactions.

9.
Phys Chem Chem Phys ; 25(18): 12641-12649, 2023 May 10.
Article in English | MEDLINE | ID: mdl-36847568

ABSTRACT

Most of the experimental and theoretical work in hole interactions (HIs) is mainly focused on exploiting the nature and characteristics of σ and π-holes. In this perspective, we focus our attention on understanding the origin and properties of lone-pair holes. These holes are present on an atom opposite to its lone-pair region. Utilizing some new and old examples, such as X3N/P⋯F- (X = F/Cl/Br/I), F-Cl/Br/I⋯H3P⋯NCH and H3B-NBr3 along with other molecular systems, we explored to what extent these lp-holes participate in lp-hole interactions, if they participate at all.

10.
Phys Chem Chem Phys ; 25(29): 19427-19434, 2023 Jul 26.
Article in English | MEDLINE | ID: mdl-37436829

ABSTRACT

This study investigates the crystal structures of substituted thiophenes and isothiocyanates by utilizing the method of in situ cryo-crystallization to gain quantitative insights into the electronic features of sulfur-centered interactions. This work reveals that the role of sulfur as a "nucleophilic" or "electrophilic" species during non-covalent interaction is significantly influenced by its immediate chemical and electronic surroundings.

11.
Environ Res ; 233: 116506, 2023 09 15.
Article in English | MEDLINE | ID: mdl-37369307

ABSTRACT

Cancer is an intricate disease that develops as a response to a combination of hereditary and environmental risk factors, which then result in a variety of changes to the genome. The cluster of differentiation (CD44) is a type of transmembrane glycoprotein that serves as a potential biomarker for cancer stem cells (CSC) and viable targets for therapeutic intervention in the context of cancer therapy. Hyaluronic acid (HA) is a linear polysaccharide that exhibits a notable affinity for the CD44 receptor. This characteristic renders it a promising candidate for therapeutic interventions aimed at selectively targeting CD44-positive cancer cells. Treating cancer via non-viral vector-based gene delivery has changed the notion of curing illness through the incorporation of therapeutic genes into the organism. The objective of this review is to provide an overview of various hyaluronic acid-modified lipoplexes and polyplexes as potential drug delivery methods for specific forms of cancer by effectively targeting CD44.


Subject(s)
Hyaluronic Acid , Neoplasms , Humans , Hyaluronic Acid/metabolism , Drug Delivery Systems , Neoplasms/therapy , Cell Line, Tumor
12.
Drug Dev Ind Pharm ; 49(1): 129-138, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36852720

ABSTRACT

PURPOSE: Complicated intra-abdominal infection (cIAI) management involves administering antibiotics that destroy the cell wall and the genesis of bacterial lipopolysaccharide (LPS). During the infectious state, the expression of transferrin receptors upregulates on the intestinal epithelial cells, which are considered the site of infection. In the present research, transferrin decorated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) encapsulated moxifloxacin (MOX) were developed for possible targeting of the receptors in the colon. SIGNIFICANCE: This study will explore more about the incorporation of transferrin as effective coating material in targeted drug delivery. METHODS: Nanoparticles were prepared using nano-emulsification and surface modification with transferrin was done by layer-by-layer methodology and evaluated by powder X-ray diffraction (PXRD), differential scanning calorimeter (DSC), FTIR, SEM, antibacterial activity, and cellular uptake studies. RESULTS: The formulated NPs exhibit a size of ≈170 nm, PDI ≈ 0.25, zeta potential ≈-4.0 mV, drug loading ≈ 6.8%, and entrapment efficiency of 82%. Transferrin-decorated NPs exhibit tailored release for almost 12 h and in vitro antibacterial activity for 14 h. The cellular uptake studies were done on a RAW264.7 cell line for better determination of transferrin uptake of fabricated NPs. CONCLUSION: The above study circumvents around the preparation of transferrin decorated PLGA encumbered MOX NPs intended for cIAI-induced sepsis. PLGA NPs provide tailored release of MOX with primary burst and followed by sustained release. These observations confines with antibacterial activity studies. The prepared transferrin-coated NPs were stable and effectively uptaken by RAW264.7 cells. However, future studies include the preclinical investigation of these NPs in sepsis-induced murine models.


Subject(s)
Nanoparticles , Polyglycolic Acid , Mice , Animals , Polylactic Acid-Polyglycolic Acid Copolymer , Moxifloxacin , Lactic Acid , Transferrin , Drug Liberation , Anti-Bacterial Agents/pharmacology , Particle Size , Drug Carriers
13.
Inflammopharmacology ; 31(3): 1279-1288, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37038017

ABSTRACT

Simvastatin is a semisynthetic inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and is used extensively to treat atherosclerotic cardiovascular disease. Apart from the lipid-lowering effect, simvastatin has been documented to offer impressive vasorelaxant activity. However, the mechanism associated with this vasorelaxant activity has yet not been substantially explored. Thus, the present study has aimed to elucidate the mechanism(s) associated with simvastatin-induced vasorelaxation using an established rat aortic ring model. The results from the study depicted that simvastatin caused significant relaxation in aortic rings pre-contracted with phenylephrine and potassium chloride (KCl). The vasorelaxant effect of simvastatin was attenuated by methylene blue (sGC-dependent cyclic guanosine monophosphate (cGMP) inhibitor), NG-nitro-L-arginine methyl ester (L-NAME; NO synthase inhibitor), 4-aminopyridine (Kv blocker), glibenclamide (KATP blocker), and barium chloride (Kir blocker). In addition, the vasorelaxant effect of simvastatin was slightly reduced by PD123319 (angiotensin II type 2 receptor (AT2R) antagonist). However, indomethacin (COX inhibitor), 1H-[1,2,4]Ox adiazolol [4,3-α]quinoxalin-1-one (ODQ; selective soluble guanylate cyclase (sGC) inhibitor), losartan (angiotensin II type 1 receptor (AT1R) antagonist), atropine (muscarinic receptor blocker), and tetraethyl ammonium (TEA; KCa blocker) did not affect the vasorelaxant effect of simvastatin. Furthermore, simvastatin was found to attenuate the release of calcium (Ca2+) from intracellular stores in the presence of ruthenium red (ryanodine receptor, RyR inhibitor) and extracellular stores via nifedipine (voltage-operated Ca2+ channels, VOCC blocker) and SK&F96365 (receptor-operated Ca2+ channel, ROCC blocker). Thus, it can be concluded that the vasorelaxant effect of simvastatin involves NO/cGMP pathways, AT2R receptors, Ca2+ channels, and K+ channels.


Subject(s)
Calcium Channels , Vasodilator Agents , Rats , Animals , Vasodilator Agents/pharmacology , Calcium Channels/metabolism , Aorta, Thoracic , Calcium Signaling , Enzyme Inhibitors , Endothelium, Vascular
14.
AAPS PharmSciTech ; 24(7): 179, 2023 Sep 02.
Article in English | MEDLINE | ID: mdl-37658972

ABSTRACT

Numerous neurodegenerative conditions, such as Alzheimer's, Huntington's, Parkinson's, amyotrophic lateral sclerosis, and glioblastoma multiform are now becoming significant concerns of global health. Formulation-related issues, physiological and anatomical barriers, post-administration obstacles, physical challenges, regulatory limitations, environmental hurdles, and health and safety issues have all hindered successful delivery and effective outcomes despite a variety of treatment options. In the current review, we covered the intranasal route, an alternative strategic route targeting brain for improved delivery across the BBB. The trans-nasal pathway is non-invasive, directing therapeutics directly towards brain, circumventing the barrier and reducing peripheral exposure. The delivery of nanosized vesicles loaded with drugs was also covered in the review. Nanovesicle systems are organised in concentric bilayered lipid membranes separated with aqueous layers. These carriers surmount the disadvantages posed by intranasal delivery of rapid mucociliary clearance and enzymatic degradation, and enhance retention of drug to reach the site of target. In conclusion, the review covers in-depth conclusions on numerous aspects of formulation of drug-loaded vesicular system delivery across BBB, current marketed nasal devices, significant jeopardies, potential therapeutic aids, and current advancements followed by future perspectives.


Subject(s)
Glioblastoma , Neurodegenerative Diseases , Humans , Neurodegenerative Diseases/drug therapy , Nose , Drug Delivery Systems , Brain
15.
AAPS PharmSciTech ; 24(8): 223, 2023 Nov 10.
Article in English | MEDLINE | ID: mdl-37945928

ABSTRACT

Rivastigmine hydrogen tartrate (RHT) is an acetylcholinesterase (AChE) inhibitor used in the management of Alzheimer's disease (AD). RHT is a BCS class-I drug that undergoes significant first-pass metabolism. Permeating a hydrophilic drug through the brain remains a major challenge in brain delivery. In this study, the RHT was incorporated inside the hydrophilic core of liposomes (LPS) and then coated with the ApoE3. ApoE3-coated RHT-loaded liposomes (ApoE3-RHT-LPS) were fabricated through the thin film hydration method using DSPE-PEG. The coating of LPS with ApoE3 enhances brain uptake and improves Aß clearance. The results obtained from the physicochemical characterization demonstrated that ApoE3-RHT-LPS shows a particle size of 128.6 ± 2.16 nm and a zeta potential of 16.6 ± 1.19. The % entrapment efficiency and % drug loading were found to be 75% and 17.84%, respectively. The data obtained from TEM and SEM studies revealed that the particle size of the LPS was less than 200 nm. An in vitro AChE assay was performed, and the results demonstrated the AChE inhibitory potential of ApoE3-RHT-LPS. Through the intravenous route, an in vivo pharmacokinetic study of formulation displayed improved brain uptake of RHT by ~ 1.3-fold than pure RHT due to ApoE3 coating. In vivo, biodistribution studies in vital organs suggested that the biodistribution of RHT to the liver was significantly reduced (p < 0.001), signifying an increase in the drug's half-life and blood circulation time. All research findings suggested that ApoE3 coating and LPS strategy are proven effective for improving the brain uptake of RHT designed for the management of AD.


Subject(s)
Alzheimer Disease , Liposomes , Humans , Rivastigmine , Liposomes/chemistry , Apolipoprotein E3/metabolism , Apolipoprotein E3/pharmacology , Acetylcholinesterase/metabolism , Acetylcholinesterase/pharmacology , Acetylcholinesterase/therapeutic use , Tissue Distribution , Lipopolysaccharides , Brain/metabolism , Cholinesterase Inhibitors , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Particle Size
16.
Biomacromolecules ; 23(4): 1519-1544, 2022 04 11.
Article in English | MEDLINE | ID: mdl-35274937

ABSTRACT

Microneedles are one of the most prominent approaches capable of physically disrupting the stratum corneum without devastating the deeper tissues to deliver both small molecules and macromolecules into the viable epidermis/dermis for local/systemic effects. Over the past two decades, microneedles have caught the attention of many researchers because of their outstanding advantages over oral and parenteral drug delivery systems such as self-administration, pain-free, steady-plasma concentration maintenance, avoidance of first-pass hepatic biotransformation, and so on. So far, scientists have reported various types of microneedle patches to deliver the loaded therapeutics as soon as the microneedles are inserted into the skin, regardless of the demand for therapeutics to treat a specific condition. This way of drug delivery can lead to potential risks such as poor therapeutic efficacy or drug overdose. The stimuli-responsive microneedles are the most predominant tool to achieve the on-demand/need-based drug delivery, leading to safe and effective treatment. Various natural and synthetic polymers that can undergo significant transitions such as swelling, shrinking, dissolution, or disintegration play a pivotal role in the development of stimuli-responsive microneedles. The current Review provides brief information about the history, emergence, type, and working principles of microneedles. Furthermore, it selectively discusses various exogenous and endogenous stimuli-responsive microneedles along with their mechanism of action involved in treating different disease conditions. Collaterally, the emergence of "closed-loop" combinatorial stimuli-responsive microneedle patches for precise delivery of therapeutics is meticulously canvassed. Subsequently, it covers the patents of different stimuli-responsive microneedles and further highlights the existing challenges and future perspectives concerning clinical application and large-scale production.


Subject(s)
Needles , Skin Absorption , Administration, Cutaneous , Drug Delivery Systems , Microinjections , Skin
17.
Int J Environ Health Res ; 32(8): 1815-1826, 2022 Aug.
Article in English | MEDLINE | ID: mdl-33886400

ABSTRACT

At the end of 2019 and 2020s, a wave of coronavirus disease 19 (COVID-19) epidemics worldwide has catalyzed a new era of 'communicable infectious diseases'. However, the world is not currently prepared to deal with the growing burden of COVID-19, with the unexpected arrival of Hantavirus infection heading to the next several healthcare emergencies in public. Hantavirus is a significant class of zoonotic pathogens of negative-sense single-stranded ribonucleic acid (RNA). Hemorrhagic renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) are the two major clinical manifestations. Till date, there is no effective treatments or vaccines available, public awareness and precautionary measures can help to reduce the spread of hantavirus disease. In this study, we outline the epidemiology, virology, clinical aspects, and existing HFRS and HCPS management approaches. This review will give an understanding of virus-host interactions and will help for the early preparation and effective handling of further outbreaks in an ever-changing environment.


Subject(s)
COVID-19 , Hantavirus Infections , Hemorrhagic Fever with Renal Syndrome , Orthohantavirus , COVID-19/epidemiology , Disease Outbreaks , Orthohantavirus/genetics , Hantavirus Infections/epidemiology , Hemorrhagic Fever with Renal Syndrome/epidemiology , Humans
18.
AAPS PharmSciTech ; 23(7): 236, 2022 Aug 24.
Article in English | MEDLINE | ID: mdl-36002713

ABSTRACT

Piperine (PIP) is a neuroprotective phytomedicine that has profound acetylcholine esterase and reactive oxygen species inhibition effect in Alzheimer's disease (AD) model. However, the oral delivery of PIP is limited by poor aqueous solubility and low bioavailability in systemic circulation. To improve the PIP bioavailability, the polyamidoamine (PAMAM) G4 dendrimer is grafted with tocopheryl polyethylene glycol succinate-1000 (TPGS) through carbodiimide chemistry to form TPGS-PAMAM conjugate. The TPGS-PAMAM coupling was confirmed through proton NMR and FTIR techniques. PIP was encapsulated in the TPGS-PAMAM through solvent diffusion method to form PIP-TPGS-PAMAM. The particle size for PIP-TPGS-PAMAM found the less than 50 nm, whereas entrapment efficiency found to 87 ± 3.5% and 10.6 ± 2.9% drug loading. The powder differential scanning calorimetry and powder X-ray diffraction characterization were employed to evaluate the amorphous encapsulation of the PIP in TPGS-PAMAM. The PIP-TPGS-PAMAM stability was studied in the gastric fluids which showed no drastic difference in particle size and encapsulation efficiency compared to PIP-PAMAM. The in vitro release analysis revealed 37 ± 4.1% PIP release from the PIP-TPGS-PAMAM matrix, and 71 ± 4.9% PIP release from the PIP-PAMAM dendrimer was observed in 48 h. The single-dose oral gavage to Wistar rats of PIP-TPGS-PAMAM showed the AUC0-∞ 14.38 µg/mL.h, Cmax 7.77 ± 1.65 µg/mL, Tmax, 1.6 ± 0.18 h, and half-life 3.47 ± 0.64 h for PIP in systemic circulation. PIP-PAMAM and free PIP showed significantly poor AUC0-∞ compared to PIP-TPGS-PAMAM. The brain uptake studies revealed PIP-TPGS-PAMAM treated group showed 2.2 ± 0.37 µg/g PIP content compared to free PIP administered group which was 0.4 ± 0.10 µg/g. Therefore, PIP-TPGS-PAMAM can offer excellent prospect for the delivery hydrophobic drugs to brain in AD.


Subject(s)
Dendrimers , Alkaloids , Animals , Benzodioxoles , Brain , Dendrimers/chemistry , Drug Carriers/chemistry , Particle Size , Piperidines , Polyamines , Polyethylene Glycols/chemistry , Polyunsaturated Alkamides , Powders , Rats , Rats, Wistar , Succinates , Succinic Acid , Vitamin E/chemistry
19.
AAPS PharmSciTech ; 23(5): 125, 2022 Apr 26.
Article in English | MEDLINE | ID: mdl-35474400

ABSTRACT

The accumulation of amyloid-beta at the neuronal sites is a major pathological hallmark involved in the etiology of Alzheimer's disease. To reduce the Aß-induced neuronal cytotoxicity, selenium nanoparticles and silymarin were fabricated in a single polysaccharide matrix for dual antioxidant and Aß fibril disaggregation activity. These nanoparticles were further stabilized by an exopolysaccharide xanthan gum. The nanoparticles were fabricated to reduce the amyloid-induced cytotoxicity in SH-SY5Y cells. A three-step method employing redox reaction of sodium selenite and ascorbic acid has been adopted for the synthesis of selenium nanoparticles. Consequently, xanthan gum powder was added to impart stability to the nanocarriers. The nanoparticles exhibited a particle size of 119.2 ± 2.8 nm, zeta potential of - 35.4 ± 3.8 mV, and % EE of 87.7 ± 2.23. HR-TEM with EDX analysis confirmed the presence of spherical nanoparticles. An in vitro drug release study exhibited 89.33 ± 5.4% release of silymarin from nanocarriers and was able to scavenge 90% free radicals of DPPH reagent. The thioflavin T (ThT) fibrillation kinetics study showed that the nanoparticles elicited maximum disaggregation of Aß fibrils that was depicted by the quenched fluorescence intensity signal. The cell viability results revealed that the highest neuroprotection activity was observed in the cell group treated with SLY-XG-Se against Aß 1-42-induced toxicity. The nanoparticles were able to internalize in SH-SY5Y cells. Our findings showed that the nanocarrier elicited anti-aggregation efficacy in neuronal cell lines and mitigated the Aß-induced cytotoxicity, which represents the prospects of neuroprotection involved in the therapeutics of AD.


Subject(s)
Selenium , Silymarin , Amyloid , Amyloid beta-Peptides/metabolism , Polysaccharides, Bacterial , Silymarin/pharmacology
20.
Phys Chem Chem Phys ; 23(36): 19948-19963, 2021 Sep 22.
Article in English | MEDLINE | ID: mdl-34514473

ABSTRACT

Hole interactions are known by different names depending on the key atom of the bond (halogen bond, chalcogen bond, hydrogen bond, etc.), and the geometry of the interaction (σ if in line, π if perpendicular to the Lewis acid plane). However, its origin starts with the creation of a Lewis acid by an underlying covalent bond, which forms an electrostatic depletion and a virtual antibonding orbital, which can create non-covalent interactions with Lewis bases. In this (maybe subjective) perspective, we will claim that hole interactions must be defined via the molecular orbital origin of the molecule. Under this premise we can better explore the richness of such bonding patterns. For that, we will study old, recent and new systems, trying to pinpoint some misinterpretations that are often associated with them. We will use as exemplars the triel bonds, a couple of metal complexes, a discussion on convergent σ-holes, and many cases of anti-electrostatic hole interactions.

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