RESUMEN
Some breast cancers are caused by hormonal imbalances, such as estrogen and progesterone. These hormones play a function in directing the growth of cancer cells. The hormone receptors in hormone receptor-positive breast cancer lead breast cells to proliferate out of control. Cancer therapy such as hormonal, targeted, radiation is still unsatisfactory because of these challenges namely multiple drug resistance (MDR), off-targeting, severe adverse effects. A novel aromatase inhibitor exemestane (Exe) exhibits promising therapy in breast cancer. This study aims to develop and optimize Exe-loaded lipid nanocapsules (LNCs) by using DSPC, PF68 and olive oil as lipid, surfactant and oil phase, respectively and to characterize the same. The prepared nanocapsules were investigated via in vitro cell culture and in vivo animal models. The LNCs exhibited cytotoxicity in MCF-7 cell lines and enhanced anti-cancer activity and reduced cardiotoxicity in DMBA-induced animal model when compared to the drug. Additionally, in vivo pharmacokinetics revealed a 4.2-fold increased oral bioavailability when compared with Exe suspension. This study demonstrated that oral administration of Exe-loaded LNCs holds promise for the antiestrogenic activity of exemestane in breast cancer.
Asunto(s)
Nanocápsulas , Neoplasias , Animales , Liposomas , Androstadienos/farmacología , Androstadienos/uso terapéutico , Lípidos , Neoplasias/tratamiento farmacológicoRESUMEN
Hepatocellular carcinoma (HCC) is a major cause of concern as it has substantial morbidity associated with it. Previous reports have ascertained the antiproliferative activity of imatinib mesylate (IMS) against diverse types of carcinomas, but limited bioavailability has also been reported. The present study envisaged optimized IMS-loaded lactoferrin (LF)-modified PEGylated liquid crystalline nanoparticles (IMS-LF-LCNPs) for effective therapy of IMS to HCC via asialoglycoprotein receptor (ASGPR) targeting. Results displayed that IMS-LF-LCNPs presented an optimum particle size of 120.40 ± 2.75 nm, a zeta potential of +12.5 ± 0.23 mV, and 73.94 ± 2.69% release. High-resolution transmission electron microscopy and atomic force microscopy were used to confirm the surface architecture of IMS-LF-LCNPs. The results of cytotoxicity and 4,6-diamidino-2-phenylindole revealed that IMS-LF-LCNPs had the highest growth inhibition and significant apoptotic effects. Pharmacokinetics and biodistribution studies showed that IMS-LF-LCNPs have superior pharmacokinetic performance and targeted delivery compared to IMS-LCNPs and plain IMS, which was attributed to the targeting action of LF that targets the ASGPR in hepatic cells. Next, our in vivo experiment established that the HCC environment existed due to suppression of BAX, cyt c, BAD, e-NOS, and caspase (3 and 9) genes, which thus owed upstream expression of Bcl-xl, iNOS, and Bcl-2 genes. The excellent therapeutic potential of IMS-LF-LCNPs began the significant stimulation of caspase-mediated apoptotic signals accountable for its anti-HCC prospect. 1H nuclear magnetic resonance (serum) metabolomics revealed that IMS-LF-LCNPs are capable of regulating the disturbed levels of metabolites linked to HCC triggered through N-nitrosodiethylamine. Therefore, IMS-LF-LCNPs are a potentially effective formulation against HCC.
Asunto(s)
Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/dietoterapia , Mesilato de Imatinib/farmacología , Lactoferrina/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Nanopartículas/química , Animales , Disponibilidad Biológica , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Células Hep G2 , Humanos , Cristales Líquidos/química , Neoplasias Hepáticas/genética , Masculino , Mitocondrias/genética , Tamaño de la Partícula , Polietilenglicoles/química , Ratas , Ratas Wistar , Distribución Tisular/efectos de los fármacosRESUMEN
The objective of the present study was to characterize intrinsic physiological and biochemical properties of the wall-less unicellular cholorophyte Dunaliella salina isolated from a hypersaline Sambhar Lake. The strain grew optimally at 0.5 M NaCl and 16:8 h L:D photoperiod along with maintaining low level of intracellular Na+ even at higher salinity, emphasizing special features of its cell membranes. It was observed that the cells experienced stress beyond 2 M NaCl as evidenced by increased intracellular reactive oxygen species and antioxidative enzymes, nevertheless proline and malondialdehyde content declined sharply accompanied by higher neutral lipid accumulation. Salinity exceeding 2 M resulted decrease in photosynthetic quantum yield (Fv/Fm) and enhanced glycerol synthesis accompanied by leakage. Super oxide dismutase seemed to play a pivotal role in antioxidative defense as eight isoforms were expressed differentially while catalase and glutathione peroxidase showing no significant change in their expression at higher salinity. The ability of D. salina to grow in range of salinities by sustaining healthy photosynthetic apparatus along with accumulation of valuable products made this alga an ideal organism that can be exploited as resource for biofuel and commercial products.
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Chlorophyta , India , Lagos , Salinidad , Cloruro de SodioRESUMEN
Identification of protein targets that play a role in breast cancer invasion may help to understand the rapid progression of cancer and may lead to the development of new biomarkers for the disease. In this study, we compared two highly invasive and two poorly invasive breast cancer cell lines using comparative label-free LC-MS profiling in order to identify differentially expressed proteins that may be linked to the invasive phenotype in vitro. Forty-five proteins were found to be upregulated, and 34 proteins, downregulated. UV excision repair protein RAD23 homologue B (RAD23B) was found among the downregulated proteins in highly invasive breast cancer cell lines. In poorly invasive breast cancer cell lines, siRNA-mediated downregulation of RAD23B subsequently led to an increase in invasion and adhesion in vitro. Immunohistochemistry analysis of 164 specimens of invasive breast cancer showed that having a high percentage (>80%) of RAD23B positive nuclei was significantly associated with histopathological grades 1 and 2 breast cancer and with low mitotic activity. In addition, a high staining intensity for RAD23B in the cytoplasm was significantly associated with histopathological grade 3 breast cancer. This study suggests a potential role of RAD23B in breast cancer progression and may further imply a tumor suppressor role of nuclear RAD23B in breast cancer.
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Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Enzimas Reparadoras del ADN/metabolismo , Proteínas de Unión al ADN/metabolismo , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/mortalidad , Carcinoma Ductal de Mama/prevención & control , Línea Celular Tumoral , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Progresión de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Receptores de Estrógenos/metabolismo , Espectrometría de Masas en TándemRESUMEN
Targeted therapies enhance the efficacy of tumour screening and management while lowering side effects. Multiple tumours, including liver cancer, exhibit elevated levels of folate receptor expression. This research attempted to develop surface-functionalised bosutinib cubosomes against hepatocellular carcinoma. The novelty of this work is the anti-hepatic action of bosutinib (BST) and folic acid-modified bosutinib cubosomes (BSTMF) established through proto-oncogene tyrosine-protein kinase (SrC)/ focal adhesion kinase(FAK), reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and cell cytotoxicity. Later, the in-vivo pharmacokinetics of BSTMF were determined for the first time. The strong affinity of folic acid (FA) for folate receptors allows BSTMF to enter cells via FA receptor-mediated endocytosis. The particle size of the prepared BSTMF was 188.5 ± 2.25 nm, and its zeta potential was -20.19 ± 2.01 mV, an encapsulation efficiency of 90.31 ± 3.15 %, and a drug release rate of 76.70 ± 2.10 % for 48 h. The surface architecture of BSTMF was identified using transmission electron microscopy (TEM) and Atomic force microscopy (AFM). Cell-line studies demonstrated that BSTMF substantially lowered the viability of Hep G2 cells compared to BST and bosutinib-loaded cubosomes (BSTF). BSTMF demonstrated an elevated BST concentration in tumour tissue than in other organs and also displayed superior pharmacokinetics, implying that they hold potential against hepatic cancers. This is the first study to show that BSTMF may be effective against liver cancer by targeting folate receptors and triggering SrC/FAK-dependent apoptotic pathways. Multiple parameters demonstrated that BSTMF enhanced anticancer targeting, therapeutic efficacy, and safety in NDEA-induced hepatocellular carcinoma.
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Compuestos de Anilina , Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Nitrilos , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Ácido Fólico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Línea Celular Tumoral , Tamaño de la PartículaRESUMEN
Orally targeted delivery systems have attracted ample interest in colorectal cancer management. In this investigation, we developed Inositol hexaphosphate (IHP) loaded Tripolyphosphate (Tr) crosslinked Pectin (Pe) Chitosan (Ch) nanoparticles (IHP@Tr*Pe-Ch-NPs) and modified them with l-Carnitine (CE) (CE-IHP@Tr*Pe-Ch-NPs) to improve uptake in colon cells. The formulated CE-IHP@Tr*Pe-Ch-NPs displayed a monodisperse distribution with 219.3 ± 5.5 nm diameter and 30.17 mV surface charge. Cell-line studies revealed that CE-IHP@Tr*Pe-Ch-NPs exhibited excellent biocompatibility in J774.2 and decreased cell viability in DLD-1, HT-29, and MCF7 cell lines. More cell internalization was seen in HT-29 and MCF7 due to overexpression of the OCTN2 and ATB0,+ transporter (CE transporters) compared to DLD-1. The cell cycle profile, reactive oxygen species, apoptosis, and mitochondrial membrane potential assays were performed to explore the chemo-preventive mechanism of CE-IHP@Tr*Pe-Ch-NPs. Moreover, the in-silico docking studies revealed enhanced interactive behavior of CE-IHP@Tr*Pe-Ch-NPs, thereby proving their targeting ability. All the findings suggested that CE-IHP@Tr*Pe-Ch-NPs could be a promising drug delivery approach for colon cancer targeting.
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Quitosano , Nanopartículas , Humanos , Ácido Fítico , Pectinas/farmacología , Carnitina , Células MCF-7 , Colon , Portadores de FármacosRESUMEN
Herein, we have demonstrated a facile method for the synthesis of CeO2/Ce-Co-LDH heterostructures using zeolitic imidazolate framework-67 as the precursor. The Ce-incorporation in Co-LDH results in 4f-2p-3d orbital overlap to tune the electronic structure whereas the oxygen-deficient CeO2 controls the interface charge transfer. This results in excellent water oxidation activity to attain 500 mA cm-2 current density at 320 overpotential.
RESUMEN
N-alkylation of anilines by alcohols can be used as an efficient strategy to synthesise a wide range of secondary amines. In this respect, a hydrogen borrowing methodology has been explored using precious metal-based catalysts. However, the utilisation of cheap and readily available transition metal based catalysts is required for large-scale applications. In this work, we have reported metal-organic framework-derived CoNx@NC catalysts for the selective N-alkylation of anilines with different types of alcohols. The Co-N coordination in CoNx@NC was found to be extremely important to improve the conversion efficiency and yield of the product. As a result, CoNx@NC produced 99% yield of the desired amines, which is far better than that of Co@C (yield = 65%). In addition, CoNx@NC showed remarkable recyclability for six cycles with a minimum drop in the yield of the desired product.
RESUMEN
Herein, we have demonstrated Lewis acid Fe(III)-assisted hydroxylation of ZIF-67 to form FexCo-layered double hydroxide (LDH) nanosheets. The catalyst Fe0.4Co-LDH produced an excellent water oxidation activity to reach a current density of 20 mA cm-2 at only 190 mV overpotential, superior to that of hydrothermally synthesized LDH with a similar composition.
Asunto(s)
Hierro , Agua , Hidroxilación , Ácidos de LewisRESUMEN
The blood-brain barrier (BBB) regulates blood and chemical exchange in the central nervous system. It is made up of brain parenchyma capillary endothelial cells. It separates the interstitial cerebrospinal fluid from the circulation and limits brain drug entry. Peptides, antibodies, and even tiny hydrophilic biomolecules cannot flow across the BBB due to their semi-permeability. It protects the brain from poisons, chemicals, and pathogens, and blood cells penetrate brain tissue. BBB-facilitated carrier molecules allow selective permeability of nutrients such as D-glucose, L-lactic acid, L-phenylalanine, L-arginine, and hormones, especially steroid hormones. Brain barriers prevent drug molecules from entering, making medication delivery difficult. Drugs can reach specific brain regions through the nasal cavity, making it a preferred route. The in-situ gels are mucoadhesive, which extends their stay in the nasal cavity, allows them to penetrate deep and makes them a dependable way of transporting numerous medications, including peptides and proteins, straight into the central nervous system. This approach holds great potential for neurological therapy as they deliver drugs directly to the central nervous system, with less interference and better drug release control. The brain affects daily life by processing sensory stimuli, controlling movement and behaviour, and sustaining mental, emotional, and cognitive functioning. Unlike systemic routes, the nasal mucosa is extensively vascularized and directly contacts olfactory sensory neurons. Compared to the systemic circulation, this improves brain bioavailability of medications. Drugs can be delivered to the brain using in-situ gel formulations safely and efficiently, with a greater therapeutic impact than with traditional techniques.
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Encéfalo , Células Endoteliales , Humanos , Encéfalo/metabolismo , Barrera Hematoencefálica/metabolismo , Péptidos/metabolismo , Geles/química , Hormonas , Sistemas de Liberación de Medicamentos/métodos , Administración IntranasalRESUMEN
Rheumatoid arthritis (RA) is a joint ailment with multi-factorial immune-mediated degenerative pathogenesis, including genetic and environmental defects. Resistance to disease-modifying anti-rheumatic drugs (DMARDs) happens due to excessive drug efflux over time, rendering the concentration insufficient to elicit a response. Thymoquinone (TQ) is a quinone-based phenolic compound with antioxidant and anti-inflammatory activities that downregulate numerous pro-inflammatory cytokines. However, its pharmaceutical importance and therapeutic utility are underexplored due to intrinsic physicochemical characteristics such as inadequate biological stability, short half-life, low hydrophilicity, and less systemic availability. Tamanu oil-stabilised nanostructured lipid carriers (TQ-NLCs) were prepared and optimised using Box-Behnken design (BBD) with the size of 153.9 ± 0.52 nm and surface charge of -30.71 mV. The % entrapment efficiency and drug content were found to be 84.6 ± 0.50% and 14.75 ± 0.52%, respectively. Furthermore, the TQ-loaded NLCs (TQ-NLCs) assayed for skin permeation for transdermal delivery which significantly (p < 0.05) increased skin enhancement ratio 14.6 times compared to the aqueous solution of TQ. Tamanu oil displayed the synergistic anti-inflammatory potential with TQ in comparison to pure TQ, as evidenced against carrageenan (CRG)-induced paw oedema model and Freund's adjuvant-induced arthritic model. The arthritic and X-ray scores significantly (p < 0.05) reduced in TQ-NLCs and standard formulation-treated groups. Moreover, serum pro-inflammatory marker TNF-α and IL-6 levels were also significantly (p < 0.05) reduced in TQ-NLCs gel-treated group compared to the arthritic control group.
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Antirreumáticos , Artritis Reumatoide , Antiinflamatorios/farmacología , Artritis Reumatoide/tratamiento farmacológico , Regulación hacia Abajo , Portadores de Fármacos/química , Interleucina-6 , Quinonas/uso terapéutico , Factor de Necrosis Tumoral alfa/metabolismo , AnimalesRESUMEN
Selenium (Se) is an essential element for living systems, however, toxic at higher levels. In the present study, Dunaliella salina cells were exposed to different Se concentrations for their growth (EC50 195 mg L-1) as well as Se accumulation. The cells exposed to 50 mg L-1 Se showed photoautotrophic growth parallel to control and accumulated 65 µg Se g-1 DW. A decrease in photosynthetic quantum yield, chlorophyll content, and the increase in intracellular reactive oxygen species, proline content, and lipid peroxidation accompanied by higher neutral lipid accumulation, were recorded at higher Se level. The enzymes superoxide dismutase and catalase played a pivotal role in antioxidative defense. Heterogeneity in accumulated carotenoids at varying concentrations of selenium was prevalent. The cells exposed to 200 mg L-1 Se resulted in the disorganization of organelles. Thus, the Se enriched biomass obtained at 50 mg L-1 may be explored for bio-fortification of food and feed.
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Microalgas , Selenio , Antioxidantes/metabolismo , Selenio/toxicidad , Especies Reactivas de Oxígeno , Microalgas/metabolismo , Bioacumulación , Fotosíntesis , Clorofila , LípidosRESUMEN
Polysaccharide-based nanoparticles (NPs) such as pectin/ chitosan (PN/CN) had always been of greatest interest because of their excellent solubility, biocompatibility, and higher suitability for oral drug delivery. This study employed blending-crosslinking of polymers (PN&CN) followed by emulsification-solvent evaporation to prepare and compare two sets of PEGylated NPs to deliver phytic acid (IP6) to colon orally as it has potential to manage colon cancer but fails to reach colon when ingested in pure form. The first set was crosslinked with Glutaraldehyde (GE) (GE*PN-CN-NPs) while the second set was crosslinked with sodium tripolyphosphate (TPP) (TPP*PN-CN-NPs). IP6-loaded-GE/TPP*PN-CN-NPs were optimized using a central composite design. Developed TPP*PN-CN-NPs had a smaller size (210.6 ± 7.93 nm) than GE*PN-CN-NPs (557.2 ± 5.027 nm). Prepared NPs showed <12% IP6 release at pH 1.2 whereas >80% release was observed at pH 7.4. Further, NPs were explored for cytocompatibility in J774.2 cell lines, cytotoxicity, and cellular uptake in HT-29 and DLD-1 cell lines. While exhibiting substantial cytotoxicity and cellular uptake in HT-29 and DLD-1, the NPs were deemedsafe in J774.2. The PEGylated-TPP*PN-CN-NPs showed time-dependent uptake in J774.2 cell lines. Conclusively, the employed NP development method successfully delivered IP6 to colon and may also open avenues for the oral delivery of other drugs to colon.
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Quitosano , Nanopartículas , Ácido Fítico , Pectinas , Colon , Polietilenglicoles , Portadores de FármacosRESUMEN
Nanoparticles (NPs) as nanocarriers have emerged as novel and promising theranostic agents. The term theranostics revealed the properties of NPs capable of diagnosing the disease at an early stage and/or treating the disease. Such NPs are usually developed employing a surface engineering approach. The theranostic agents comprise NPs loaded with a drug/diagnostic agent that delivers it precisely to the target site. Theranostics is a field with promising results in enhancing therapeutic efficacy facilitated through higher payload at the targeted tissue, reduced dose, and dose-dependent side effects. However, controversies in terms of toxicity and size-dependent properties have often surfaced for NPs. Thus, a stringent in-vitro and in-vivo evaluation is required to develop safe and non-toxic NPs as theranostic agents. The review also focuses on the various entry points of NPs in the human system and their outcomes, including toxicity. It elaborates the evaluation criteria to ensure the safe use of NPs for diagnostic and therapeutic purposes.
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Nanopartículas , Nanoestructuras , Humanos , Nanopartículas/uso terapéutico , Medicina de Precisión , Nanomedicina Teranóstica/métodosRESUMEN
AIM: Felodipine (FDP), an antihypertensive drug possesses low water solubility and extensive first-pass metabolism leading to poor bioavailability. This impelled us to improve its solubility, bioavailability, and pharmacodynamic properties through the Nanocrystal (NC) approach. METHODS: FDP-NC were prepared with Poloxamer F125 (PXM) by the antisolvent precipitation method. The experimental setup aimed at fine-tuning polymer concentration, the proportion of antisolvent to solvent, and the duration of ultrasonication for NC formulation. RESULTS: Optimized formulation was characterized for particle size, solubility, and PDI. Particle reduction of 74.96 times was achieved with a 9X solubility enhancement as equated to pure FDP. The morphology of NC was found to be crystalline through scanning electron microscopy observation. The formation of the crystal lattice in FDP-NC was further substantiated by the XRD and DSC results. Lowering of the heat of fusion of FDP-NC is a clear indication of size reduction. The stability studies showed no substantial change in physical parameters of the FDP-NC as assessed by particle size, zeta potential, and drug content. CONCLUSION: The crystalline nature and improved solubility of FDP-NC improve the dissolution profile and pharmacodynamic data. The stability study data ensure that FDP-NC can be safely stored at 25°C. It is revealed that FDP-NC had a better release profile and improved pharmacodynamic effects as evident from better control over heart rate than FDP.
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Hipertensión , Nanopartículas , Animales , Disponibilidad Biológica , Cloruro de Cadmio , Felodipino/química , Felodipino/farmacología , Nanopartículas/química , Tamaño de la Partícula , Ratas , SolubilidadRESUMEN
Limited targeted therapies are available for triple-negative breast cancer (TNBC). Thus, the current research focused on developing a targeted protein nanoparticle for TNBC. First, the doxorubicin hydrochloride (Dox)-loaded genipin-crosslinked whey protein nanoparticles (WD) were prepared and optimised by the QbD method using BBD. The hydrodynamic diameter of WD was found to be 364.38 ± 49.23 nm, zeta potential -27.59 ± 1.038 mV, entrapment 63.03 ± 3.625% and Dox loading was found to be 1.419 ± 0.422%. The drug recovery after 18 months of storage was 69%. Then, it was incubated with NAC to obtain modified WD (CyWD). WD followed first-order release kinetics, whereas CyWD followed the Higuchi model. Hemagglutination and hemolysis were not found qualitatively in WD and CyWD. Upon injecting the nanoformulations to 4T1-induced mice, the highest efficacy was found to be in CyWD followed by WD and Dox injection. Upon histopathological observance, it was found that the CyWD group gave the most significant damage to the 4T1 tumour tissue. Thus, NAC-modified protein nanoparticles carrying chemotherapeutic agents can be an excellent targeted therapeutic system against TNBC.
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Nanopartículas , Neoplasias de la Mama Triple Negativas , Humanos , Ratones , Animales , Doxorrubicina/farmacología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Proteína de Suero de Leche/uso terapéutico , Acetilcisteína , Línea Celular TumoralRESUMEN
Aim: To assess the targeting ability of hybrid nanosystems functionalized with folate. It also aimed to reduce stomach intolerance by substituting the oral route for parenteral delivery. Method: The nanosystems, prepared by nanoprecipitation technique, utilized a one-step method to prepare nanoparticles followed by surface functionalization through adsorption. The prepared nanosystems underwent physical characterization, in vitro and in vivo evaluations. Result: The nanosystems were effective in targeting the alveolar macrophages. Ethionamide was released from the formulation over 5 days. Fourier-transform infrared results proved the structural characteristics, and the positive charge further improved the targeting efficacy on the functionalized system. Conclusion: The hybrid formulation improved the release characteristics. Reduction in dosing frequency due to prolonged release improves compliance with the dosage regimen.
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Quitosano , Nanopartículas , Etionamida , Macrófagos Alveolares , Ácido Fólico/química , Transporte Biológico , Nanopartículas/química , Quitosano/química , Espectroscopía Infrarroja por Transformada de Fourier , Portadores de Fármacos/química , Sistemas de Liberación de MedicamentosRESUMEN
This study was designed to create surface-functionalized bosutinib liposomes that could be used for the management of estrogen-positive cancers. The novelty of this work was the anti-cancer activity of bosutinib-loaded liposomes (Bos-LPs) in estrogen-positive cancer via estrogen response elements, responsible for the malignancy of cancer cells. Biotin effectively delivers active moiety to tumor tissues because it interacts with the biotin receptor and operates through the Sodium-dependent multivitamin transporters (SMVT) transporter. The prepared liposomes had a 257.73 ± 4.50 nm particle size, - 28.07 ± 5.81 mV zeta potential, 87.78 ± 1.16 % encapsulation efficiency and 85.56 ± 0.95 % drug release for 48 h. The surface architecture of biotin-modified bosutinib-loaded liposomes (b-Bos-LPs) was confirmed using scanning electron and transmission electron microscopies. In-vitro experiments revealed that b-Bos-LPs outperformed Bos and Bos-LPs in terms of significantly reduced cell viability in MCF-7 cells. According to biodistribution and pharmacokinetic studies, b-Bos-LPs have a higher Bos concentration in tumor tissues as compared to the other organs and also possess better pharmacokinetic activity, indicating that they can be used to treat carcinogen-induced estrogen-positive cancers. This is the first study to show that b-Bos-LPs can display activity against estrogen-positive cancer via biotin targeting. As evidenced by various parameters, b-Bos-LPs showed improved anticancer targeting, therapeutic safety and efficacy in carcinogen-induced estrogen-positive cancer. The receptor protein estrogen, which is primarily responsible for this cancer was downregulated by b-Bos-LPs in an immunoblotting assay. The results showed that biotinylated distearoylphosphatidylcholine (DSPC) augmented LPs loaded with Bosutinib can cause apoptosis in estrogen-positive breast cancer and be an effective way to treat estrogen-positive cancer.
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Compuestos de Anilina , Neoplasias de la Mama , Liposomas , Nitrilos , Quinolinas , Compuestos de Anilina/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Estrógenos/metabolismo , Femenino , Humanos , Nitrilos/uso terapéutico , Tamaño de la Partícula , Quinolinas/uso terapéuticoRESUMEN
This study aimed at the development of hyaluronic acid-functionalised imatinib mesylate cubosomes (HA-IM-CBs) that might be useful in CD44 targeting against hepatic cancer. The HA-IM-CBs had a 130.7⯱â¯2.92â¯nm particle size, -31.40⯱â¯2.76â¯mV zeta potential, and 76.14⯱â¯2.69% release. The architecture of HA-IM-CBs was confirmed using HR-TEM and AFM. When compared to plain IM and IM-CBs, in vitro experiments revealed that HA-IM-CBs outperformed by significantly reducing cell viability. DAPI staining and ROS corroborated the apoptotic effects. Biodistribution and Pharmacokinetics studies showedthat HA-IM-CBs exhibit a higher drug concentration in tumour tissue and better pharmacokinetic activity. This is the first study to show that HA-IM-CBs had CD44 targeting activity against HCC. CD44 regulates apoptosis via Bcl-2 family proteins and caspases, which interact with HA. Higher levels of e-NOS, BAD, BAX, and Cyt C and lower expressions of Bcl-xl, i-NOS, and Bcl-2 demonstrated the anti-HCC potential of HA-IM-CBs in qrt-PCR investigations. The remarkable therapeutic potential of HA-IM-CBs began with substantial stimulation of CD44 regulated caspase-mediated mitochondrial apoptotic pathway, accountable for their anti-HCC activity. The perturbed metabolites are restored to acceptable levels as indicated by metabolomic studies (1H NMR). Interestingly, the antineoplastic effect of HA-IM-CBs was proven to be potentially valuable against HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamiento farmacológico , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Humanos , Receptores de Hialuranos/metabolismo , Ácido Hialurónico/química , Mesilato de Imatinib/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Proteínas Proto-Oncogénicas c-bcl-2 , Distribución TisularRESUMEN
There is a curious case in Alveolar macrophages (AM), the frontline defence recruits that contain the spread of all intruding bacteria. In response to Mycobacterium tuberculosis (M.tb), AM either contain the spread or are modulated by M.tb to create a region for their replication. The M.tb containing granulomas so formed are organised structures with confined boundaries. The limited availability of drugs inside AM aid drug tolerance and poor therapeutic outcomes in diseases like tuberculosis. The present work proves the glycotargeting efficiency of levofloxacin (LVF) to AM. The optimised formulation developed displayed good safety with 2% hemolysis and a viability of 61.14% on J774A.1 cells. The physicochemical characterisations such as Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) proved that carubinose linkage was accomplished and LVF is entrapped inside carubinose-linked hybrid formulation (CHF) and hybrid formulation (HF) in amorphous form. The transmission electron microscopy (TEM) images revealed a core-shell structure of HF. The particle size of 471.5 nm estimated through dynamic light scattering (DLS) is enough to achieve active and passive targeting to AM. The nanoparticle tracking analysis (NTA) data revealed that the diluted samples were free from aggregates. Fluorescence-activated cell sorting (FACS) data exhibited excellent uptake via CHF (15 times) and HF(3 times) with reference to plain fluorescein isothiocyanate (FITC). The pharmacokinetic studies revealed that CHF and HF release the entrapped moiety LVF in a controlled manner over 72 h. The stability studies indicated that the modified formulation remains stable over 6 months at 5 ± 3â. Hence, hybrid systems can be efficiently modified via carubinose to target AM via the parenteral route.