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1.
Artigo em Inglês | MEDLINE | ID: mdl-38400898

RESUMO

The present work aims to develop and evaluate the wound healing potential of bakuchiol nanoemulsion loaded electrospun scaffolds. Since oxidative stress and microbial burden leads the burn wounds to become chronic and fatal to patients, a phytoconstituent, bakuchiol (BAK), was screened on the basis of antioxidant and antimicrobial potential which also defined its dose. Furthermore, BAK was incorporated into a nanoemulsion to enhance its therapeutic efficacy, reduce its dosage frequency, and maximize its stability. The present study is inclined towards the collaborative interaction of natural products and novel drug delivery systems to develop safe and therapeutically efficient systems for burn wound healing. The optimized nanoemulsion showed excellent antioxidant and antimicrobial potential against wound susceptible pathogens, i.e., Candida albicans and Methicillin-resistant Staphylococcus aureus which was further loaded into gelatin based hydrogel and nanofibrous scaffold system. The mesh structure of scaffolds was chosen as a suitable carrier system for wound healing process not only because it offers resemblance to skin's anatomy but is also capable of providing uniform distribution of wound biomarkers across the skin. The prepared nanofibers were assessed for their analgesic, anti-inflammatory, and wound healing potential which was observed to be significantly better than its gel formulation.

3.
Biofouling ; 39(9-10): 962-979, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38009008

RESUMO

The current work aims to develop a shikonin and tea tree oil loaded nanoemulsion system stabilized by a mixture of GRAS grade surfactants (Tween 20 and monoolein) and a cosurfactant (Transcutol P). This system was designed to address the poor aqueous solubility and photostability issues of shikonin. The authenticity of shikonin employed in this study was confirmed using nuclear magnetic resonance (NMR) spectroscopy. The optimized nanoemulsion exhibited highly favorable characteristics in terms of zeta potential (-23.8 mV), polydispersity index (0.216) and particle size (22.97 nm). These findings were corroborated by transmission electron microscopy (TEM) micrographs which confirmed the spherical and uniform nature of the nanoemulsion globules. Moreover, attenuated total reflectance (ATR) and X-ray diffraction analysis (XRD) analysis affirmed improved chemical stability and amorphization, respectively. Photodegradation studies were performed by exposing pure shikonin and the developed nanoemulsion to ultraviolet light for 1 h using a UV lamp, followed by high performance liquid chromatography (HPLC) analysis. The results confirmed that the developed nanoemulsion system imparts photoprotection to pure shikonin in the encapsulated system. Furthermore, the research investigated the effect of the nanoemulsion on biofilms formed by Candida albicans and methicillin resistant Staphylococcus aureus (MRSA). Scanning electron microscopy, florescence microscopy and phase contrast microscopy unveiled a remarkable reduction in biofilm area, accompanied by disruptions in the cell wall and abnormalities on the cell surface of the tested microorganisms. In conclusion, the nanoencapsulation of shikonin with tea tree oil as the lipid phase showcased significantly enhanced antimicrobial and antibiofilm potential compared to pure shikonin against resistant strains of Candida albicans and Staphylococcus aureus.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Naftoquinonas , Óleo de Melaleuca , Candida albicans , Óleo de Melaleuca/farmacologia , Staphylococcus aureus , Biofilmes , Anti-Infecciosos/farmacologia , Testes de Sensibilidade Microbiana
5.
Arch Pharm (Weinheim) ; 356(8): e2200579, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37276367

RESUMO

The objective of the present investigation was to prepare and optimize lyophilized mixed micelles (Lyp-EXE-MMs) of exemestane (EXE) with improved solubility, bioavailability, in vivo anticancer activity, and physical stability, by using various cryoprotectants. The prepared lyophilized mixed micelles were characterized by various techniques, including dynamic light scattering, zeta potential, powdered X-ray diffraction, differential scanning calorimetry (DSC), nuclear magnetic resonance (1 H NMR), transmission electron microscopy (TEM), and so on. Thereafter, the lyophilized micelles were evaluated for ex vivo permeation, in vitro drug release and gene/protein expression (RT-PCR and Western blot analysis) in MCF-7 breast cancer cells. The developed formulation was also investigated for its in vivo anticancer study in BALB/c mice with induced breast cancer. The use of trehalose (10% w/w) was proven to be a suitable cryoprotectant for these micelles. Lyp-EXE-MMs were spherical, with a particle size of 42.9 ± 3.8 nm and a polydispersity index of 0.307 ± 0.122. Furthermore, % drug loading and % entrapment efficiency were found to be 5.8 ± 1.4 and 89.1 ± 1.1, respectively. Lyp-EXE-MMs showed sustained release behavior as compared to EXE-suspensions in SGF/SIF (pH 1.2 and 6.8) and phosphate buffer saline (pH 7.4). The micelles induced apoptosis through the regulation of BAX, BCL2, Caspase-3, p53, and CYP19A1 in MCF-7 cells, which was correlated to enhanced ex vivo drug permeation. Animals receiving EXE micelle formulations showed reduced tumor volume and improved survivability and pharmacokinetic parameters as compared to pure EXE. Lyp-EXE-MMs were found to withstand simulated harsh conditions of SGF/SIF during stability studies. The fabricated EXE micellar preparations hold a promising approach for breast cancer treatment.


Assuntos
Androstadienos , Micelas , Animais , Camundongos , Relação Estrutura-Atividade , Solubilidade , Androstadienos/química , Androstadienos/farmacocinética , Portadores de Fármacos/química
6.
Sci Rep ; 13(1): 4461, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36932199

RESUMO

Mitochondrial impairment, energetic crisis and elevated oxidative stress have been demonstrated to play a pivotal role in the pathological processes of Huntington's disease (HD). 3-Nitropropionic acid (3-NPA) is a natural neurotoxin that mimics the neurological dysfunctions, mitochondrial impairments and oxidative imbalance of HD. The current investigation was undertaken to demonstrate the neuroprotective effect of 4-(methylthio)butyl isothiocyanate (4-MTBITC) against the 3-NPA induced neurotoxicity in human dopaminergic SH-SY5Y cells. The experimental evidence of oxidative DNA damage by 3-NPA was elucidated by pBR322 DNA nicking assay. In contrast, the 4-MTBITC considerably attenuated the DNA damage, suggesting its free radical scavenging action against 3-NPA and Fenton's reagent. The dose and time-dependent increase of 3-NPA revealed its neurotoxic dose as 0.5 mM after 24 h of treatment of SH-SY5Y cells in MTT assay. In order to determine the optimal dose at which 4-MTBITC protects cell death, the 3-NPA (IC50) induced cells were pretreated with different concentrations of 4-MTBITC for 1 h. The neuroprotective dose of 4-MTBITC against 3-NPA was found to be 0.25 µM. Additionally, the elevated GSH levels in cells treated with 4-MTBITC indicate its propensity to eliminate reactive species generated as a result of 3-NPA-induced mitochondrial dysfunction. Likewise, it was determined through microscopic and flow cytometric experiments that 3-NPA's induced overproduction of reactive species and a decline in mitochondrial membrane potential (MMP) could be efficiently prevented by pre-treating cells with 4-MTBITC. To elucidate the underlying molecular mechanism, the RT-qPCR analysis revealed that the pre-treatment of 4-MTBITC effectively protected neuronal cells against 3-NPA-induced cell death by preventing Caspase-3 activation, Brain-derived neurotrophic factor (BDNF) upregulation, activation of cAMP response element-binding protein (CREB) and Nrf2 induction. Together, our findings lend credence to the idea that pre-treatment with 4-MTBITC reduced 3-NPA-induced neurotoxicity by lowering redox impairment, apoptotic state, and mitochondrial dysfunction. The present work, in conclusion, presented the first proof that the phytoconstituent 4-MTBITC supports the antioxidant system, BDNF/TrkB/CREB signaling, and neuronal survival in dopaminergic SH-SY5Y cells against 3-NPA-induced oxidative deficits.


Assuntos
Neuroblastoma , Fármacos Neuroprotetores , Humanos , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/farmacologia , Estresse Oxidativo , Neurônios Dopaminérgicos , Oxirredução , Fármacos Neuroprotetores/farmacologia , Apoptose , Sobrevivência Celular , Linhagem Celular Tumoral
7.
Naunyn Schmiedebergs Arch Pharmacol ; 396(9): 2105-2125, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36929274

RESUMO

The aim of the current study is to evaluate the anti-psoriatic potential of bakuchiol (Bak) loaded solid lipid nanoparticles (SLNs) via modulating inflammatory and oxidative pathways. Bak-loaded SLNs were prepared using hot homogenization method and characterized by various spectroscopic techniques. Bak-SLNs suspension was formulated into gel using Carbopol. Different in vivo assays were executed to explore the role of inflammatory markers and oxidative enzymes in psoriasis. DLS (dynamic light scattering) analysis showed suitable particle size, zeta potential, and polydispersity index (PDI) of developed formulation. TEM (transmission electron microscopy) reveal the spherical shape of Bak-SLNs particles. The release studies confirmed the sustained release of Bak-SLNs-based gel. UV-B-induced psoriatic Wistar rat model showed significant anti-psoriatic effect of Bak via regulating inflammatory markers (NF-kB, IL-6, IL-4, and IL-10) and levels of anti-oxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and glutathione-S-transferase (GST). Furthermore, RT-qPCR analysis confirms that Bak downregulates the expression of inflammatory markers, while histology and immunohistology results also confirm the anti-psoriatic effect of Bak. The study indicates that Bak-loaded SLNs-based gel significantly downregulates the level of cytokines and interleukins involve in NF-kB signaling cascade; hence, it can prove to be a novel therapeutic approach to cure psoriasis.


Assuntos
Nanopartículas , Psoríase , Ratos , Animais , NF-kappa B , Ratos Wistar , Psoríase/tratamento farmacológico , Nanopartículas/química , Glutationa , Transdução de Sinais , Portadores de Fármacos/química
8.
Arch Microbiol ; 205(3): 93, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36800037

RESUMO

In the recent past, the occurrence of fungal infections has increased drastically and candidiasis, caused prominently by Candida albicans, is foremost among them which has caused significant mortality and morbidity majorly in immune-compromised patients. Shikonin is a well-known natural naphthazarin derivative with promising antifungal efficacy, but it's mechanism of action is still unclear. Keeping this in view, present work was designed to get a mechanistic insight of anti-candida efficacy of shikonin via in vitro experiments and in situ molecular modelling studies. The current exploratory study is based on research that uses both qualitative and quantitative techniques, including minimum inhibitory concentration, minimum biofilm inhibitory concentration, time kill assay, cell cycle analysis and apoptotic assays, static biofilm formation assays, microscopic biofilm assessment assays, ergosterol content estimation and molecular docking/simulation studies. The study revealed a notable effect of shikonin against Candida albicans, including retardation of biofilms. Shikonin, with its increasing concentration leads to candidal cell apoptosis and necrosis establishing its dose-dependent effect. Additionally, it exhibited fungicidal activity via a mechanism of action likely related to ergosterol complexation which was further corroborated by molecular docking and simulation studies.


Assuntos
Candida albicans , Naftoquinonas , Humanos , Simulação de Acoplamento Molecular , Candida , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Naftoquinonas/farmacologia , Testes de Sensibilidade Microbiana , Biofilmes , Ergosterol
9.
Cancer Lett ; 556: 216065, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36642326

RESUMO

Proteolysis-targeting chimeras (PROTACs) are being developed as an effective method for degrading cancer-related proteins by modifying the endogenous ubiquitin-proteasome system. To investigate the dynamics between an E3 ligase and target protein, researchers have developed a wide variety of bifunctional PROTACs by combining small molecule ligands. These PROTACs employ numerous ligands, some of which are reversible, some of which are irreversible, some attach to orthosteric sites, while others bind to allosteric sites. Some are agonists, while others are antagonists, and the target protein may be activated in either a positive or negative manner. A variety of targeted ligand approaches can be used to enhance PROTAC properties, including tumor selectivity and drug delivery, and to overcome drug resistance. The processes and behaviors of small molecule-based PROTACs and targeted proteolysis approaches as anticancer therapeutic molecules have been introduced in this mini-review.


Assuntos
Neoplasias , Complexo de Endopeptidases do Proteassoma , Proteólise , Ubiquitina-Proteína Ligases , Humanos , Ligantes , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas/metabolismo , Proteólise/efeitos dos fármacos , Ubiquitina-Proteína Ligases/metabolismo
10.
Biotechnol Genet Eng Rev ; : 1-25, 2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36683273

RESUMO

Multidrug resistance (MDR) is considered as a major obstacle in achieving an effective treatment of breast cancer. Paclitaxel has been used to treat cancers of the cervical, breast, ovarian and brain but MDR limits its therapeutic potential. Phytochemicals have received much interest in recent decades especially in combination approaches to tackle MDR due to their negligible harm to healthy cells and synergistic potential. Considering this notion, the present study aimed at investigating the synergistic activity of 4-MTBITC and PTX against a panel of breast cancer cells. Our results revealed that the combination had a significant antiproliferative activity against T-47D cells. Mechanistic studies revealed that 4-MTBITC and PTX also promoted the production of reactive oxygen species (ROS) and reduced mitochondrial membrane potential. In the presence of 4-MTBITC- PTX, T-47D cells were found to be arrested in the G2/M phase which also confirmed the enhancement of late apoptotic cell population in the flow cytometer analysis. In western blot experiment, the combination had a significant decrease in Bcl-xl protein level, whereas a higher level of p53, cleaved caspase-3, and cleaved caspase-9 proteins compared to individual treatment in T-47D cells. The RT-qPCR analysis also showed that the combination had significant upregulation in the gene expression of p53, cytochrome-c, Apaf-1 and downregulation in the expression of Bcl-2 gene in T-47D cells. Hence, all the results showed that a combination of 4-MTBITC-PTX significantly enhanced the apoptosis pathway in the T-47D cell line which indicates its clinical application for the treatment of breast cancer.Abbreviations: Apaf-1: Apoptotic protease activating factor 1; AO/EB: Acridine orange/ethidium bromide; Bcl-2: B-cell lymphoma 2; CI: Combination Index; Cyt-c: Cytochrome c; CO2: Carbon dioxide; DCFH-DA 2,7-Dichloroflourescein diacetate; DMEM: Dulbecco's modified Eagle's medium; ELISA: Enzyme-linked immunosorbent assay; EA: Early apoptosis; EDTA: Ethylenediaminetetraacetic acid; L929: Normal mouse fibroblast cells; LA: Late apoptosis; L: Live; 4-MTBITC: 4-methylthiobutyl isothiocyanate; MCF-7: Human breast cancer cells; MDA-MB-231: Human triple negative breast cancer cells; MMP: Mitochondria membrane potential; MTT: 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide; NCCS: National Centre for Cell Science; N: Necrotic; PTX Paclitaxel; PVDF: Polyvinylidene fluoride; PAGE: Polyacrylamide gel electrophoresis; PBS: Phosphate-buffered saline; RPMI-1640: Roswell Park Memorial Institute Medium- 1640; RT-qPCR: Quantitative real-time polymerase chain reaction; ROS: Reactive oxygen species; Rh-123: Rhodamine123; g Relative centrifugal force; SDS: Sodium dodecyl sulphate; SEM: Scanning electron microscopy; T-47D: Human estrogen positive breast cancer cells; WB: Western blotting.

11.
Front Pharmacol ; 13: 1020602, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330087

RESUMO

Nanoformulation-based combinational drug delivery systems are well known to overcome drug resistance in cancer management. Among them, nanoemulsions are well-known and thermodynamically stable drug delivery systems suitable for carrying hydrophobic drugs and phytoconstituents to tackle drug-resistant cancers. In the present study, we have investigated the effect of paclitaxel in combination with erucin (natural isothiocyanate isolated from the seeds of Eruca sativa) loaded in the frankincense oil-based nanoemulsion formulation. The choice of frankincense oil for the current study was based on reported research investigations stating its magnificient therapeutic potential against breast cancer. Optimized nanoemulsion of paclitaxel (PTX) and erucin (ER) combination (EPNE) provided sustained release and exhibited enhanced cytotoxicity towards human epithelial breast cancer cells (T-47D) as compared to individual ER and PTX. EPNE was further assessed for its antitumor activity in the 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast cancer mice model. EPNE significantly decreased the levels of hepatic and renal parameters along with oxidative stress in breast cancer mice. Furthermore, EPNE also showed decreased levels of inflammatory cytokines TNF-α, IL-6. Histopathological examinations revealed restoration of the tumorous breast to normal tissues in EPNE-treated breast cancer mice. Therefore, EPNE can act as a viable lead and therapeutic option for drug-resistant breast cancer.

12.
Chin Herb Med ; 14(4): 511-527, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36405061

RESUMO

Alkannin/shikonin (A/S) and their derivatives are naturally occurring naphthoquinones majorly found in Boraginaceae family plants. They are integral constituents of traditional Chinese medicine Zicao (roots of Lithospermum erythrorhizon). In last two decades significant increase in pharmacological investigations on alkannin/shikonin and their derivatives has been reported that resulted in discovery of their novel mechanisms in various diseases and disorders. This review throws light on recently conducted pharmacological investigations on alkannin/shikonin and their derivatives and their outputs. Various analytical aspects are also discussed and brief summary of patent applications on inventions containing alkannin/shikonin and its derivatives is also provided.

13.
Artigo em Inglês | MEDLINE | ID: mdl-36200152

RESUMO

Cancer is a worldwide health ailment with no known boundaries in terms of mortality and occurrence rates, thus is one of the biggest threats to humankind. Hence, there is an absolute need to develop novel therapeutics to bridge the infirmities associated with chemotherapy and conventional surgical methodologies including impairment of normal tissue, compromised drug efficiency and an escalation in side effects. In lieu of this, there's been a surge in curiosity towards development of injectable hydrogels for cancer therapy because local administration of the active pharmaceutical agent offers encouraging advantages such as providing higher effective dose at target site, prolonged retention time of drug, ease of administration, mitigation of dose in vivo ,improved patient compliance. Furthermore, due to its biocompatible nature such systems can significantly reduce the side effects that occur on long-term exposure to chemotherapy. The present review details the most recent advancements in in-situ gel forming polymers (natural and synthetic), polymeric cross-linking methodologies and in-situ gelling mechanisms, focusing on their clinical benefits in cancer therapy.

14.
Assay Drug Dev Technol ; 20(4): 137-148, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35674685

RESUMO

Antibiotic polymer conjugates (APCs) are an essential part of polymer therapeutics. These conjugates have been used as an appealing platform for drug delivery. As a delivery vector, the administration route severely impacts the accessibility of antibiotics to their respective target site and therapeutic index. Furthermore, the physicochemical and biological properties of conjugates also correlate distinctly with the route of administration. The APCs delivery methods that have been disclosed so far suffer from significant constraints due to poor technology and constrained administration routes (mainly injections). Leading to promising directions, which include the development of specific characteristics for each polymer carrier, application of novel biodegradable polymers, expansion of traditional drug administration routes through the development of emerging routes, and the development of a rational and systematic methodology for designing administration routes are yet to be explored widely. This review focuses primarily on recent improvements in various routes of administration (dental, topical, and ocular) employing APCs. The mechanism of action, as well as other perspectives, have also been discussed. Moreover, this innovative technology provides a fresh perspective on pharmaceutical science research and offers unique and potential pathways for designing desired APCs.


Assuntos
Antibacterianos , Polímeros , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Sistemas de Liberação de Medicamentos , Polímeros/química
15.
Toxicon ; 212: 19-33, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35395273

RESUMO

4-(methylthio)butyl isothiocyanate (4-MTBITC) also called erucin is abundantly present in the seeds of Eruca sativa plant closely related to cruciferous vegetables rich in isothiocyanates. We have previously reported the molecular targets of 4-MTBITC, but no acute, subacute and subchronic toxicity studies have been carried out to evaluate its safety. The non-everted gut sac method was used to study intestinal absorption and it revealed the highest absorption of 4-MTBITC in the jejunum. Dose-dependent pharmacokinetic parameters were observed in rats given 10, 20, and 40 mg/kg oral doses of 4-MTBITC. At the highest dose of 40 mg/kg, Cmax was 437.33 µg/ml and Tmax was 30 min, suggesting quick absorption and delayed elimination with elimination constant, 0.0036 ± 0.0002min-1. In a 14 days toxicity study, the mean LD50 of 4-MTBITC was 500 mg/kg body weight. After 28 and 90 days of treatment with 4-MTBITC (2.5, 10, 40 mg/kg/day), significant increases were observed in SGOT, cholesterol, and antioxidant enzymes. The levels of glycine, alanine and lysine were markedly increased in the liver tissue, thereby indicating that the liver was the target organ of 4-MTBITC induced toxicity in female animals. The histopathological examination of liver, kidney, and lung tissues revealed little focal necrosis, apoptosis, and reduction in the levels of amino acids involved in cellular metabolic pathways, indicating the anti-proliferative potential of 4-MTBITC against rapidly growing cells.


Assuntos
Apoptose , Isotiocianatos , Animais , Feminino , Isotiocianatos/toxicidade , Extratos Vegetais , Ratos
16.
Recent Adv Drug Deliv Formul ; 16(1): 55-67, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35236278

RESUMO

Shikonin and its derivatives are excellent representatives of biologically active naphthoquinones. A wide range of investigations carried out in the last few decades validated their pharmacological efficacy. Besides having magnificent therapeutic potential, shikonin and its derivatives suffer from various pharmacokinetic, toxicity, and stability issues like poor bioavailability, nephrotoxicity, photodegradation, etc. Recently, various research groups have developed an extensive range of formulations to tackle these issues to ease their path to clinical practice. The latest formulation approaches have been focused on exploiting the unique features of novel functional excipients, which in turn escalate the therapeutic effect of shikonin. Moreover, the codelivery approach in various drug delivery systems has been taken into consideration in a recent while to reduce toxicity associated with shikonin and its derivatives. This review sheds light on the essential reports and patents published related to the array of formulations containing shikonin and its derivatives.


Assuntos
Naftoquinonas , Sistemas de Liberação de Medicamentos , Naftoquinonas/farmacologia
17.
Environ Sci Pollut Res Int ; 29(12): 17189-17208, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34664164

RESUMO

Argemone mexicana(Pepaveraceae) is an important medicinal plant commonly known as 'maxican prickly poppy' and is traditionally used to treat skin diseases. In the present study, the extract/fractions of aerial parts of A. mexicana after carrying out the organoleptic characteristics were sequentially extracted with the solvents of increasing polarities. Total fractions were examined for their radical scavenging activities in DPPH and DNA nicking assays. Among all, maximum antioxidant activity was shown by chloroform fraction (AmC) in DPPH assay with IC50 of 26.12 µg/ml, and DNA nicking assay showed 80.91% protective potential. The AmC fraction was analyzed for its antibacterial, cytotoxic potential, cell cycle analysis, mitochondrial membrane potential (MMP) and accumulation of reactive oxygen species (ROS) using A431 cell line. The AmC fraction exhibited remarkable antibacterial activity against bacterial strains in the order Klebsiella pneumoniae> Bacillussubtilis> Salmonella typhi> Staphylococcus epidermidis. The cytotoxic potential of the AmC fraction was analyzed in skin epidermoid carcinoma (A431) cells, osteosarcoma (MG-63) and cervical (HeLa) cell lines with a GI50 value of 47.04 µg/ml, 91.46 µg/ml and 102.90 µg/ml, respectively. The AmC fraction was extended further to explore its role in cell death using A431 cell line. Phase contrast and scanning electron microscopic studies on A431 cells exhibited all the characteristics indicative of apoptosis, viz., viability loss, cell shrinkage, cell rounding-off, DNA fragmentation and formation of apoptotic bodies. Flow cytometric analysis revealed enhanced ROS level, decreased MMP and arrest cell cycle at the G0/G1 phase further strengthened cell death by apoptosis. Increased expressions of apoptotic markers (p53, PUMA, cyt c, Fas and Apaf-1) were confirmed by RT-qPCR analysis. Furthermore, the AmC fraction was subjected to ultra-high-performance liquid chromatography, which revealed the presence of different polyphenols in the order: caffeic acid> epicatechin> kaempferol> chlorogenic acid> gallic acid> catechin> ellagic acid >umbeliferone> quercetin> coumaric acid. A critical analysis of results revealed that the AmC fraction induced cell death in epidermoid carcinoma cells via ROS and p53-mediated apoptotic pathway which may be ascribed to the presence of polyphenols in it.


Assuntos
Apoptose , Argemone , Extratos Vegetais , Argemone/química , Linhagem Celular Tumoral , Clorofórmio , Humanos , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/metabolismo
18.
Curr Drug Deliv ; 19(5): 560 - 586, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34906056

RESUMO

The conventional anticancer chemotherapies not only cause serious toxic effects but also produce resistance in tumor cells exposed to long-term therapy. Usually, the selective killing of metastasized cancer cells requires long-term therapy with higher drug doses because the cancer cells develop resistance due to the induction of poly-glycoproteins (P-gps) that act as a transmembrane efflux pump to transport drugs out of the cells. During the last few decades, scientists have been exploring new anticancer drug delivery systems such as microencapsulation, hydrogels, and nanotubes to improve bioavailability, reduce drug-dose requirement, decrease multiple drug resistance, and save normal cells as non-specific targets. Hopefully, the development of novel drug delivery vehicles (nanotubes, liposomes, supramolecules, hydrogels, and micelles) will assist in delivering drug molecules at the specific target site and reduce undesirable side effects of anticancer therapies in humans. Nanoparticles and lipid formulations are also designed to deliver a small drug payload at the desired tumor cell sites for their anticancer actions. This review will focus on the recent advances in drug delivery systems and their application in treating different cancer types in humans.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Sistemas de Liberação de Medicamentos , Humanos , Hidrogéis/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia
19.
Front Pharmacol ; 13: 1080977, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36761468

RESUMO

The study on Erucin (ER) has gained interest of nutraceutical and pharmaceutical industries because of its anti-cancer properties. Erucin is an isothiocyanate obtained from the seeds of Eruca sativa which possess certain drawbacks such as poor aqueous solubility and bioavailability. Therefore, the present study aimed at developing ER-cubosomes (CUB) by solvent evaporation technique followed by applying Central Composite Design to optimize ER loaded cubosomes. For this purpose, independent variables selected were Monoolein (MO) as lipid and Pluronic-84 (P-84) as a stabilizer whereas dependent variables were particle size, percentage of ER loading and percentage of its entrapment efficiency. The cubosomal nanocarriers exhibited particle size in the range of 26 nm, entrapment efficiency of 99.12 ± 0.04% and drug loading of 3.96 ± 0.0001%. Furthermore, to investigate the antioxidant potential, we checked the effect of ER and ER-CUB by DNA nicking assay, DDPH assay and Phosphomolybdate assay, and results showed significant improvement in antioxidant potential for ER-CUB than ER. Similarly, ER-CUB showed enhanced anticancer activity with a marked reduction in IC50 value than ER in MTT assay. These results suggested that ER-CUB produced notable escalation in antioxidant potential and enhanced anticancer activity than ER.

20.
Assay Drug Dev Technol ; 19(6): 386-401, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34339259

RESUMO

Humans have been dealing with health problems for millions of years. Normal health services need well-trained personnel and high-cost diagnostic tests, which forces patients to go to hospitals if medical treatment is required. To address this, prototype testing has been carried out into the wearable drug delivery health care perspectives. Researchers have devised a wide variety of formulations for the treatment of various diseases at home by performing real-time monitoring of different routes of drug administration such as ocular, transdermal, intraoral, intracochlear, and several more. A comprehensive review of the different types of wearable drug delivery systems with respect to their manufacturing, mechanism of action and specifications has been done. In the pharmaceutical context, these devices are technologically well-equipped interfaces for diverse physicochemical signals. Above mentioned information with a broader perspective has also been discussed in this article. Several wearable drug delivery systems have been introduced in the market in recent years. But a lot of testing needs to be conducted to address the numerous obstacles before the wearable devices are successfully launched in the market.


Assuntos
Preparações Farmacêuticas , Dispositivos Eletrônicos Vestíveis , Sistemas de Liberação de Medicamentos , Humanos
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