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1.
Cytokine ; 171: 156376, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37748333

RESUMO

Cancer involves cells' abnormal growth and ability to invade or metastasize to different body parts. Cancerous cells can divide uncontrollably and spread to other areas through the lymphatic or circulatory systems. Tumors form when malignant cells clump together in an uncontrolled manner. In this context, the cytokine interferon-gamma (IFN-γ) is crucial in regulating immunological responses, particularly malignancy. While IFN-γ is well-known for its potent anti-tumor effects by activating type 1 immunity, recent research has revealed its ability to suppress type 2 immunity, associated with allergy and inflammatory responses. This review aims to elucidate the intricate function of IFN-γ in inhibiting type 2 immune responses to cancer. We explore how IFN-γ influences the development and function of immune cells involved in type 2 immunity, such as mast cells, eosinophils, and T-helper 2 (Th2) cells. Additionally, we investigate the impact of IFN-mediated reduction of type 2 immunity on tumor development, metastasis, and the response to immunotherapeutic interventions. To develop successful cancer immunotherapies, it is crucial to comprehend the complex interplay between type 2 and type 1 immune response and the regulatory role of IFN-γ. This understanding holds tremendous promise for the development of innovative treatment approaches that harness the abilities of both immune response types to combat cancer. However, unraveling the intricate interplay between IFN-γ and type 2 immunity in the tumor microenvironment will be essential for achieving this goal.

2.
J Biochem Mol Toxicol ; 37(11): e23482, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37530602

RESUMO

Inflammation is an essential immune response that helps fight infections and heal tissues. However, chronic inflammation has been linked to several diseases, including cancer, autoimmune disorders, cardiovascular diseases, and neurological disorders. This has increased interest in finding natural substances that can modulate the immune system inflammatory signaling pathways to prevent or treat these diseases. Luteolin is a flavonoid found in many fruits, vegetables, and herbs. It has been shown to have anti-inflammatory effects by altering signaling pathways in immune cells. This review article discusses the current research on luteolin's role as a natural immune system modulator of inflammatory signaling mechanisms, such as its effects on nuclear factor-kappa B, mitogen-activated protein kinases, Janus kinase/signal transducer and activator of transcription, and inflammasome signaling processes. The safety profile of luteolin and its potential therapeutic uses in conditions linked to inflammation are also discussed. Overall, the data point to Luteolin's intriguing potential as a natural regulator of immune system inflammatory signaling processes. More research is needed to fully understand its mechanisms of action and possible therapeutic applications.


Assuntos
Luteolina , Neoplasias , Humanos , Luteolina/farmacologia , Luteolina/uso terapêutico , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Transdução de Sinais , Sistema Imunitário
3.
Molecules ; 27(1)2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35011497

RESUMO

Genistein is a naturally occurring polyphenolic molecule in the isoflavones group which is well known for its neuroprotection. In this review, we summarize the efficacy of genistein in attenuating the effects of memory impairment (MI) in animals. Scopus, PubMed, and Web of Science databases were used to find the relevant articles and discuss the effects of genistein in the brain, including its pharmacokinetics, bioavailability, behavioral effects, and some of the potential mechanisms of action on memory in several animal models. The results of the preclinical studies highly suggested that genistein is highly effective in enhancing the cognitive performance of the MI animal models, specifically in the memory domain, including spatial, recognition, retention, and reference memories, through its ability to reduce oxidative stress and attenuate neuroinflammation. This review also highlighted challenges and opportunities to improve the drug delivery of genistein for treating MI. Along with that, the possible structural modifications and derivatives of genistein to improve its physicochemical and drug-likeness properties are also discussed. The outcomes of the review proved that genistein can enhance the cognitive performance and ameliorate MI in different preclinical studies, thus indicating its potential as a natural lead for the design and development of a novel neuroprotective drug.


Assuntos
Encéfalo/metabolismo , Genisteína/uso terapêutico , Transtornos da Memória/tratamento farmacológico , Doenças Neuroinflamatórias/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Animais , Desenho de Fármacos , Humanos , Transtornos da Memória/metabolismo , Doenças Neuroinflamatórias/metabolismo
5.
Artigo em Inglês | MEDLINE | ID: mdl-37519208

RESUMO

The significance of Autoimmune Disorders (Ads) is underscored by their chronic nature, high maintenance costs, and complexity affecting numerous organs and tissues. A more comprehensive approach to treating Ads is required across patient populations. A revolutionary area for obtaining an integrated therapeutic option is natural phytoconstituents. Diverse biomolecules with promising properties can be found in abundance in the marine environment. Many substances have been identified from sponges, bacteria, fungi, cyanobacteria, and algae that have been shown to have immunomodulatory activities and may be used as possible treatments for Ads. Marine-derived bioactive substances have been demonstrated to affect immunological responses and to be essential in immunotherapies. The amount of information about the specific effects of substances obtained from marine sources utilized as dietary supplements or for treating immune-related diseases is growing. This paper discusses many sources of potential marine metabolic chemicals, such as maritime flora and fauna. Numerous marine phytoconstituents have recently been isolated, described, and identified, and they are currently undergoing human usage studies. We have attempted to consolidate information concerning phytoconstituents from marine sources with anti-inflammatory and immunomodulatory properties in this review, and we have briefly explored their methods of action. In order to provide a baseline of knowledge for promoting marine flora-based phytoconstituents in the current context of increasing Ads incidence, deprived of the more affordable, safe, and effective medications to combat the terrible human disease, this paper reviews the works thus far conducted on this aspect.

6.
Artigo em Inglês | MEDLINE | ID: mdl-37710065

RESUMO

Carbon nanotubes (CNTs) exposure in human beings through inhalation may affect pulmonary organs and extrapulmonary organs including liver, kidney, brain, spleen, etc. The toxic effects developed as the result of CNTs exposure made us to explore the beneficial effect of nano bis-demethoxy curcumin analog (NBDMCA) towards multi-walled carbon nanotubes (MWCNTs)-induced toxicity in extrapulmonary organs. The current study described the ameliorative effect of NBDMCA against the toxic effects developed by inhaled MWCNTs in the extrapulmonary organs. The rats are exposed to the fixed aerosol concentration of 5 mg/m3 maintained in inhalation exposure chambers MWCNTs for 15 days as per OECD guidelines. After the exposure with MWCNTs, the animals were treated with NBDMCA (5 mg/kg body weight) with different dose frequencies, i.e., 2 doses per week for 1, 2, and 4 weeks. After treatment duration, the blood was drawn from retro-orbital vein and subjected to biochemical and cytokine analysis. Further the animals were euthanized, and the sample tissues were collected and performed oxidative stress and histopathology. The study results revealed that the intravenous administration of NBDMCA suppresses the extrapulmonary toxicity induced by MWCNTs, i.e., annulling the clinical changes and oxidative stress in various extrapulmonary organs at low doses of NBDMCA, evidenced its antioxidant efficacy. Moreover, use of increased doses provides better reduction in toxic symptoms with negligible side effects confirming the dose-dependent efficacy of NBDMCA. Overall, we suggested that NBDMCA may materialize into an effective compound for the reduction of MWCNTs-induced toxicity.

7.
Pharmaceuticals (Basel) ; 16(2)2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-37259329

RESUMO

Acetylcholine (ACh) neurotransmitter of the cholinergic system in the brain is involved in learning, memory, stress responses, and cognitive functioning. It is hydrolyzed into choline and acetic acid by two key cholinesterase enzymes, viz., acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A loss or degeneration of cholinergic neurons that leads to a reduction in ACh levels is considered a significant contributing factor in the development of neurodegenerative diseases (NDs) such as Alzheimer's disease (AD). Numerous studies have shown that cholinesterase inhibitors can raise the level of ACh and, therefore, enhance people's quality of life, and, at the very least, it can temporarily lessen the symptoms of NDs. 1,2,3-triazole, a five-membered heterocyclic ring, is a privileged moiety, that is, a central scaffold, and is capable of interacting with a variety of receptors and enzymes to exhibit a broad range of important biological activities. Recently, it has been clubbed with other pharmacophoric fragments/molecules in hope of obtaining potent and selective AChE and/or BuChE inhibitors. The present updated review succinctly summarizes the different synthetic strategies used to synthesize the 1,2,3-triazole moiety. It also highlights the anticholinesterase potential of various 1,2,3-triazole di/trihybrids reported in the past seven years (2015-2022), including a rationale for hybridization and with an emphasis on their structural features for the development and optimization of cholinesterase inhibitors to treat NDs.

8.
Infect Disord Drug Targets ; 23(3): e190922208916, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36121085

RESUMO

The perspective of the people of Sub-Saharan Africa (SSA) toward both traditional and western healthcare systems varies. The goal of the current study is to examine the SSA's unique skin disease health care system. This study comprises numerous research that sought to examine how the general public feels about the SSA's current healthcare system. In this review, common skin conditions, such as atopic dermatitis, buruli ulcers, dermatophytosis, and scabies, are addressed. According to this report, government agencies must pay particular attention to skin illnesses in SSA and raise public awareness. Availability of medical care, socioeconomic factors, degree of education, and other factors influence patients' attitudes toward traditional and western health care differently in different geographic areas. Facts suggest that self-medication is the preference of the majority of patients before seeking dermatological care. The present study concludes that the magnitude of skin diseases is neglected or underestimated in many regions of SSA. Also, western healthcare facilities of many regions of SSA are not up to the mark. The present study recommends that proper access to the health care system and awareness about skin diseases through various government programs can be helpful in the regulation of skin disorders among people of SSA.


Assuntos
Atenção à Saúde , Dermatopatias , Humanos , Assistência ao Paciente , África Subsaariana/epidemiologia , Pele , Dermatopatias/tratamento farmacológico
9.
Pharmaceutics ; 15(7)2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37514105

RESUMO

Acyclovir (ACV) is a promising candidate for drug repurposing because of its potential to provide an effective treatment for viral infections and non-viral diseases, such as cancer, for which limited treatment options exist. However, its poor physicochemical properties limit its application. This study aimed to formulate and evaluate an ACV-loaded red clay nanodrug delivery system exhibiting an effective cytotoxicity. The study focused on the preparation of a complex between ACV and red clay (RC) using sucrose stearate (SS) (nanocomplex F1) as an immediate-release drug-delivery system for melanoma treatment. The synthesized nanocomplex, which had nanosized dimensions, a negative zeta potential and the drug release of approximately 85% after 3 h, was found to be promising. Characterization techniques, including FT-IR, XRD and DSC-TGA, confirmed the effective encapsulation of ACV within the nanocomplex and its stability due to intercalation. Cytotoxicity experiments conducted on melanoma cancer cell lines SK-MEL-3 revealed that the ACV release from the nanocomplex formulation F1 effectively inhibited the growth of melanoma cancer cells, with an IC50 of 25 ± 0.09 µg/mL. Additionally, ACV demonstrated a significant cytotoxicity at approximately 20 µg/mL in the melanoma cancer cell line, indicating its potential repurposing for skin cancer treatment. Based on these findings, it can be suggested that the RC-SS complex could be an effective drug delivery carrier for localized cancer therapy. Furthermore, the results of an in silico study suggested the addition of chitosan to the formulation for a more effective drug delivery. Energy and interaction analyses using various modules in a material studio demonstrated the high stability of the composite comprising red clay, sucrose stearate, chitosan and ACV. Thus, it could be concluded that the utilization of the red clay-based drug delivery system is a promising strategy to improve the effectiveness of targeted cancer therapy.

10.
Pathol Res Pract ; 249: 154738, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37595448

RESUMO

Lung cancer (LC) continues to pose a significant global medical burden, necessitating a comprehensive understanding of its molecular foundations to establish effective treatment strategies. The mitogen-activated protein kinase (MAPK) signaling system has been scientifically associated with LC growth; however, the intricate regulatory mechanisms governing this system remain unknown. Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of diverse cellular activities, including cancer growth. LncRNAs have been implicated in LC, which can function as oncogenes or tumor suppressors, and their dysregulation has been linked to cancer cell death, metastasis, spread, and proliferation. Due to their involvement in critical pathophysiological processes, lncRNAs are gaining attention as potential candidates for anti-cancer treatments. This article aims to elucidate the regulatory role of lncRNAs in MAPK signaling in LC. We provide a comprehensive review of the key components of the MAPK pathway and their relevance in LC, focusing on aberrant signaling processes associated with disease progression. By examining recent research and experimental findings, this article examines the molecular mechanisms through which lncRNAs influence MAPK signaling in lung cancer, ultimately contributing to tumor development.


Assuntos
Neoplasias Pulmonares , Sistema de Sinalização das MAP Quinases , RNA Longo não Codificante , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , RNA Longo não Codificante/metabolismo , Humanos , Epigênese Genética
11.
Artigo em Inglês | MEDLINE | ID: mdl-37017676

RESUMO

Technological advancement to enhance tumor cells (TC) has allowed discovery of various cellular bio-markers: cancer stem cells (CSC), circulating tumor cells (CTC), and endothelial progenitor cells (EPC). These are responsible for resistance, metastasis, and premetastatic conditions of cancer. Detection of CSC, CTC, and EPC assists in early diagnosis, recurrence prediction, and treatment efficacy. This review describes various methods to detect TC subpopulations such as in vivo assays (sphere-forming, serial dilution, and serial transplantation), in vitro assays (colony-forming cells, microsphere, side-population, surface antigen staining, aldehyde dehydrogenase activity, and Paul Karl Horan label-retaining cells, surface markers, nonenriched and enriched detection), reporter systems, and other analytical methods (flow cytometry, fluorescence microscopy/spectroscopy, etc.). The detailed information on methods to detect CSC, CTC, and EPC in this review will assist investigators in successful prognosis, diagnosis, and cancer treatment with greater ease.


Assuntos
Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patologia , Citometria de Fluxo , Células-Tronco Neoplásicas/patologia , Biomarcadores Tumorais
12.
Artigo em Inglês | MEDLINE | ID: mdl-37917370

RESUMO

Circular RNAs (circRNAs) have emerged as pivotal regulators of gene expression and cellular processes in various physiological and pathological conditions. In recent years, there has been a growing interest in investigating the role of circRNAs in inflammatory lung diseases, owing to their potential to modulate inflammation-associated pathways and contribute to disease pathogenesis. Inflammatory lung diseases, like asthma, chronic obstructive pulmonary disease (COPD), and COVID-19, pose significant global health challenges. The dysregulation of inflammatory responses demonstrates a pivotal function in advancing these diseases. CircRNAs have been identified as important players in regulating inflammation by functioning as miRNA sponges, engaging with RNA-binding proteins, and participating in intricate ceRNA networks. These interactions enable circRNAs to regulate the manifestation of key inflammatory genes and signaling pathways. Furthermore, emerging evidence suggests that specific circRNAs are differentially expressed in response to inflammatory stimuli and exhibit distinct patterns in various lung diseases. Their involvement in immune cell activation, cytokine production, and tissue remodeling processes underscores their possible capabilities as therapeutic targets and diagnostic biomarkers. Harnessing the knowledge of circRNA-mediated regulation in inflammatory lung diseases could lead to the development of innovative strategies for disease management and intervention. This review summarizes the current understanding of the role of circRNAs in inflammatory lung diseases, focusing on their regulatory mechanisms and functional implications.

13.
Materials (Basel) ; 15(9)2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35591502

RESUMO

Periimplantitis due to pathogenic bacteria is considered as a major cause for dental implants failures. Biogenic zinc oxide nanoparticles (ZnPs) are known to inhibit periimplantitis triggering pathogens. The current investigation intended to perform ZnPs biosynthesis and evaluation against periimplantitis triggering bacteria. The current study involved ZnPs biosynthesis using Andrographis paniculata leaves aqueous extract (APLAE), followed by optimization, stability, characterization, and in vitro evaluation against periimplantitis triggering bacteria. The experimental results indicated the success of ZnPs biosynthesis based on the optimization of zinc acetate (1.5 g), plant extract (5 mL), pH 12, and temperature (25 °C), and using the stability study (absorbance between 365-370 nm) and characterization data exhibiting broad and shifted bands (in FTIR spectrum), the size was found to be below 98.61 nm (determined by FESEM and XRD spectra) and 71.54% zinc was observed in the EDX spectrum. Biogenic ZnPs exhibited a high inhibitory activity against periimplantitis-triggering pathogens (E. coli and S. aureus). Based on the experimental results, the present study concludes that biogenic ZnPs possess a high inhibitory potential against periimplantitis-triggering bacteria, and it is established that the biosynthesis of ZnPs using APLAE is a useful method.

14.
Front Pharmacol ; 13: 902207, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35846997

RESUMO

The present work investigates a blend of jack fruit mucilage (JFM) and okra mucilage (OKM) as promising mucoadhesive carriers for colon-specific delivery of a curcumin (CMN)-loaded mucoadhesive tablet (CMT) formulation. Formulation optimization was performed using central composite design (CCD) to further decipher the effect of varying proportions of the mucoadhesive carriers JFM and OKG on response factors such as drug release (% DR) and mucoadhesive strength (MA). The optimized formulation CMT (F14) demonstrated a favorable 54.35% in vitro release of CMN in 12 h with release kinetics resulting from a zero-order anomalous diffusion mechanism and MA of 34.1733 ± 1.26 g. Accelerated stability testing of CMT (F14) confirmed a shelf life of about 4.7 years. In vivo drug targeting studies performed using rabbit models in order to observe transit behavior (colon-specific delivery) of the dosage form were assessed by fluoroscopic images of the GI tract. Taking the results together, the results confirm that the combination of JFM and OKM could be exploited as an ideal mucoadhesive carrier for effective delivery of macromolecules to the colon.

15.
Polymers (Basel) ; 14(5)2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35267860

RESUMO

The main objective of the study was to prepare tamarind seed polysaccharide grafted copolymers of polyacrylamide (TSP-g-Am) using a 32 factorial design. Tamarind seed polysaccharide (TSP) was extracted, and grafted copolymer of TSP was prepared using polyacrylamide as copolymer and ceric ammonium nitrate as initiator. Various batches (F1-F9) of TSP-g-Am were prepared, among which F1 showed highest grafting efficiency; hence, the prepared TSP-g-Am (F1) was evaluated for grafting efficiency, conversion, effect of initiator and further characterized using SEM analysis, contact angle determination, DSC analysis, swelling index, swelling and deswelling, and chemical resistance. The contact angle of TSP was found to be 81 ± 2, and that of TSP-g-Am (F1) was found to be 74 ± 2, which indicates that the wetting ability of the grafted copolymer was less than that of the native polymer. The results of thermal analysis indicated that TSP-g-Am had a more stable molecular structure than TSP. The morphology of the grafted polymer was observed from SEM images, and it was observed that the particles was asymmetrical. Antimicrobial activity was also found in the grafted copolymer. The present study concludes that the TSP-g-Am showed an excellent performance in thermal stability and swelling capacity compared with TSP. The detailed structural characteristics, as well as the excellent thermal stability and swelling capacities, will make it beneficial to use the synthesised copolymer as a precursor for the production of large-scale eco-friendly advanced materials with a wide range of applications, acting as a stabiliser, thickener, binder, release retardant, modifier, suspending agent, viscosity enhancer, emulsifying agent, or carrier for novel drug delivery systems in oral, buccal, colon, and ocular systems, and in nanofabrication and wound dressing, and it is also becoming an important part of food, cosmetics, confectionery, and bakery.

16.
Front Pharmacol ; 13: 820806, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401176

RESUMO

Curcuma longa Linn. (C. longa), popularly known as turmeric, belongs to the Zingiberaceae family and has a long historical background of having healing properties against many diseases. In Unani and Ayurveda medicine, C. longa has been used for liver obstruction and jaundice, and has been applied externally for ulcers and inflammation. Additionally, it is employed in several other ailments such as cough, cold, dental issues, indigestion, skin infections, blood purification, asthma, piles, bronchitis, tumor, wounds, and hepatic disorders, and is used as an antiseptic. Curcumin, a major constituent of C. longa, is well known for its therapeutic potential in numerous disorders. However, there is a lack of literature on the therapeutic potential of C. longa in contrast to curcumin. Hence, the present review aimed to provide in-depth information by highlighting knowledge gaps in traditional and scientific evidence about C. longa in relation to curcumin. The relationship to one another in terms of biological action includes their antioxidant, anti-inflammatory, neuroprotective, anticancer, hepatoprotective, cardioprotective, immunomodulatory, antifertility, antimicrobial, antiallergic, antidermatophytic, and antidepressant properties. Furthermore, in-depth discussion of C. longa on its taxonomic categorization, traditional uses, botanical description, phytochemical ingredients, pharmacology, toxicity, and safety aspects in relation to its major compound curcumin is needed to explore the trends and perspectives for future research. Considering all of the promising evidence to date, there is still a lack of supportive evidence especially from clinical trials on the adjunct use of C. longa and curcumin. This prompts further preclinical and clinical investigations on curcumin.

17.
Plants (Basel) ; 10(6)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34072717

RESUMO

Swertia alata C.B Clarke (Gentianaceae) is a well-reported plant in the traditional system of medicine. The present study was intended to isolate the phytoconstituents from the ethanolic extract of the aerial parts of S. alata; and evaluate for in vitro COX-1/COX-2 inhibition activity, in vivo anti-inflammatory and ulcerogenic activity. Phytoisolation involved partitioning of S. alata ethanolic extract into petroleum ether and chloroform soluble fractions using silica gel-based column chromatography. The isolation afforded two phytoisolates, namely oleanolic acid (SA-1) and 3-hydroxylup-12-(13)-ene-17-carboxylic acid (SA-4). Phytoisolates structures were established by melting point, ultraviolet (UV), attenuated total reflection-Fourier-transform infrared (ATR-FTIR), nuclear magnetic resonance (1H-NMR, 13C-NMR and HMBC) and mass spectrometry. Phytoisolates were further evaluated for in vitro cyclooxygenase (COX-1/COX-2) inhibitory activity, in vivo anti-inflammatory and ulcerogenic activity. The study revealed SA-4 (COX-1/COX-2 inhibition activity of 104/61.68 µM with % inhibition of 61.36) to be more effective than SA-1 (COX-1/COX-2 inhibition activity of 128.4/87.25 µM, with % inhibition of 47.72). SA-1 and SA-4, when subjected to ulcerogenic study, exhibited significant gastric tolerance. The current study reports chromatographic isolation and spectrometric characterization of SA-1 and SA-4. The present study concludes that compound SA-4 possess significant anti-inflammatory activity and less irritant property over gastric mucosa with no significant ulcerogenicity in comparison to indomethacin.

18.
Antioxidants (Basel) ; 10(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33477494

RESUMO

Evidence suggests that reactive oxygen species (ROS) mediate tissue homeostasis, cellular signaling, differentiation, and survival. ROS and antioxidants exert both beneficial and harmful effects on cancer. ROS at different concentrations exhibit different functions. This creates necessity to understand the relation between ROS, antioxidants, and cancer, and methods for detection of ROS. This review highlights various sources and types of ROS, their tumorigenic and tumor prevention effects; types of antioxidants, their tumorigenic and tumor prevention effects; and abnormal ROS detoxification in cancer; and methods to measure ROS. We conclude that improving genetic screening methods and bringing higher clarity in determination of enzymatic pathways and scale-up in cancer models profiling, using omics technology, would support in-depth understanding of antioxidant pathways and ROS complexities. Although numerous methods for ROS detection are developing very rapidly, yet further modifications are required to minimize the limitations associated with currently available methods.

19.
Biology (Basel) ; 10(3)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33668707

RESUMO

Evidence suggests that stem cells exert regenerative potential via the release of extracellular vesicles. Mesenchymal stem cell extracellular vesicles (MSCEVs) offer therapeutic benefits for various pathophysiological ailments by restoring tissues. Facts suggest that MSCEV action can be potentiated by modifying the mesenchymal stem cells culturing methodology and bioengineering EVs. Limited clinical trials of MSCEVs have questioned their superiority, culturing quality, production scale-up and isolation, and administration format. Translation of preclinically successful MSCEVs into a clinical platform requires paying attention to several critical matters, such as the production technique, quantification/characterization, pharmacokinetics/targeting/transfer to the target site, and the safety profile. Keeping these issues as a priority, the present review was designed to highlight the challenges in translating preclinical MSCEV research into clinical platforms and provide evidence for the regenerative potential of MSCEVs in various conditions of the liver, kidney, heart, nervous system, bone, muscle, cartilage, and other organs/tissues.

20.
Polymers (Basel) ; 13(23)2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34883720

RESUMO

Transdermal drug delivery is important to maintain plasma drug concentrations for therapeutic efficacy. The current study reports the design, formulation, and evaluation of tizanidine transdermal patches formulated using chitosan and thiolated chitosan, ethyl cellulose (EC), polyvinylpyrrolidone (PVP), and Eudragit RL100 in different ratios. The tizanidine patches were formulated using flaxseed oil and coriander oil in the concentrations of 1% v/w, 2% v/w, 3% v/w, 4% v/w, 5% v/w, and 10% v/w. The patches were subjected to characterization of physicochemical property (thickness, weight uniformity, drug content, efficiency, percentage moisture uptake/loss), in vitro drug release and drug permeation, skin irritation, in vivo application, pharmacokinetics analysis, and stability studies. The results indicate that the interaction of thiolated chitosan with the negative charges of the skin opens the tight junctions of the skin, whereas flaxseed and coriander oils change the conformational domain of the skin. The novelty of this study is in the use of flaxseed and coriander oils as skin permeation enhancers for the formulation of tizanidine transdermal patches. The formulations follow non-Fickian drug release kinetics. The FTZNE23, FTZNE36 and FTZNE54, with 5% v/w flaxseed oil loaded formulations, exhibited higher flux through rabbit skin compared with FTZNE30, FTZNE35, FTZNE42, and FTZNE47, formulations loaded with 10% v/w coriander oil. The study concludes that flaxseed oil is a better choice for formulating tizanidine patches, offering optimal plasma concentration and therapeutic efficacy, and recommends the use of flaxseed and coriander oil based patches as a novel transdermal delivery system for tizanidine and related classes of drugs.

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