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1.
Biotechnol J ; 19(3): e2300449, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38472095

ABSTRACT

Sorafenib, a multikinase inhibitor is used to treat hepatocellular and renal carcinoma. However, a low solubility impedes its bioavailability and thus, effectiveness. This study aims to enhance its effectiveness by using novel camel milk casein nanoparticles as a delivery system. This study evaluates the cytotoxicity of sorafenib encapsulated in camel milk casein nanoparticles against human hepatocarcinoma cells (HepG2 cells) in vitro. Optimal drug loaded nanoparticles were stable for 1 month, had encapsulation efficiency of 96%, exhibited a particle size of 230 nm, zeta potential of -14.4 and poly disparity index of 0.261. Treatment with it led to cell morphology and DNA fragmentation as a characteristic of apoptosis. Flow cytometry showed G1 phase arrest of cell cycle and 26% increased apoptotic cells population upon treatment as compared to control. Sorafenib-loaded casein nanoparticles showed 6-fold increased ROS production in HepG2 cells as compared to 4-fold increase shown by the free drug. Gene and protein expression studies done by qPCR and western blotting depicted upregulation of tumor suppressor gene p53, pro-apoptotic Bax, and caspase-3 along with downregulated anti-apoptotic Bcl-2 gene and protein expression which further emphasized death by apoptosis. It is concluded regarding the feasibility of these casein nanoparticles as a delivery system with enhanced therapeutic outcomes against hepatocellular carcinoma cells.


Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Nanoparticles , Animals , Humans , Sorafenib/pharmacology , Sorafenib/therapeutic use , Camelus , Caseins/pharmacology , Caseins/therapeutic use , Liver Neoplasms/metabolism , Milk , Hep G2 Cells , Antineoplastic Agents/pharmacology , Carcinoma, Hepatocellular/drug therapy , Cell Line, Tumor , Apoptosis
2.
Phytother Res ; 2024 Mar 24.
Article in English | MEDLINE | ID: mdl-38522945

ABSTRACT

Rheumatoid arthritis is a chronic autoimmune inflammatory disease characterized by immune response overexpression, causing pain and swelling in the synovial joints. This condition is caused by auto-reactive antibodies that attack self-antigens due to their incapacity to distinguish between self and foreign molecules. Dysregulated activity within numerous signalling and immunological pathways supports the disease's development and progression, elevating its complexity. While current treatments provide some alleviation, their effectiveness is accompanied by a variety of adverse effects that are inherent in conventional medications. As a result, there is a deep-rooted necessity to investigate alternate therapeutic strategies capable of neutralizing these disadvantages. Medicinal herbs display a variety of potent bioactive phytochemicals that are effective in the complementary management of disease, thus generating an enormous potency for the researchers to delve deep into the development of novel phytomedicine against autoimmune diseases, although additional evidence and understanding are required in terms of their efficacy and pharmacodynamic mechanisms. This literature-based review highlights the dysregulation of immune tolerance in rheumatoid arthritis, analyses the pathophysiology, elucidates relevant signalling pathways involved, evaluates present and future therapy options and underscores the therapeutic attributes of a diverse array of medicinal herbs in addressing this severe disease.

3.
Carbohydr Polym ; 327: 121655, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38171676

ABSTRACT

Wound dressings act as a physical barrier between the wound site and the external environment, preventing additional harm; choosing suitable wound dressings is essential for the healing process. Polysaccharide biopolymers have demonstrated encouraging findings and therapeutic prospects in recent decades about wound therapy. Additionally, polysaccharides have bioactive qualities like anti-inflammatory, antibacterial, and antioxidant capabilities that can help the process of healing. Due to their excellent tissue adhesion, swelling, water absorption, bactericidal, and immune-regulating properties, polysaccharide-based bio-adhesive films have recently been investigated as intriguing alternatives in wound management. These films also mimic the structure of the skin and stimulate the regeneration of the skin. This review presented several design standards and functions of suitable bio-adhesive films for the healing of wounds. Additionally, the most recent developments in the use of bio-adhesive films as wound dressings based on polysaccharides, including hyaluronic acid, chondroitin sulfate, dextran, alginate, chitosan, cellulose, konjac glucomannan, gellan gum, xanthan gum, pectin, guar gum, heparin, arabinogalactans, carrageen, and tragacanth gum, are thoroughly discussed. Lastly, to create a road map for the function of polysaccharide-based bio-adhesive films in advanced wound care, their clinical performances and future challenges in making bio-adhesive films by three-dimensional bioprinting are summarized.


Subject(s)
Adhesives , Polysaccharides , Polysaccharides/chemistry , Wound Healing , Bandages , Alginates/chemistry , Anti-Bacterial Agents/pharmacology
4.
AAPS PharmSciTech ; 24(7): 188, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37715004

ABSTRACT

Hydroxypropyl methylcellulose acetate succinate (HPMCAS) has multi-disciplinary applications spanning across the development of drug delivery systems, in 3D printing, and in tissue engineering, etc. HPMCAS helps in maintaining the drug in a super-saturated condition by inhibiting its precipitation, thereby increasing the rate and extent of dissolution in the aqueous media. HPMCAS has several distinctive characteristics, such as being amphiphilic in nature, having an ionization pH, and a succinyl and acetyl substitution ratio, all of which are beneficial while developing formulations. This review provides insights regarding the various types of formulations being developed using HPMCAS, including amorphous solid dispersion (ASD), amorphous nanoparticles, dry coating, and 3D printing, along with their applicability in drug delivery and biomedical fields. Furthermore, HPMCAS, compared with other carbohydrate polymers, shows several benefits in drug delivery, including proficiency in imparting stable ASD with a high dissolution rate, being easily processable, and enhancing bioavailability. The various commercially available formulations, regulatory considerations, and key patents containing the HPMCAS have been discussed in this review.


Subject(s)
Methylcellulose , Nanoparticles , Drug Delivery Systems , Biological Availability
5.
Mol Pharm ; 20(7): 3653-3671, 2023 07 03.
Article in English | MEDLINE | ID: mdl-37262335

ABSTRACT

Topical administration of anti-cancer drugs along with photodynamically active molecules is a non-invasive approach, which stands to be a promising modality for treating aggressive cutaneous melanomas with the added advantage of high patient compliance. However, the efficiency of delivering drugs topically is limited by several factors, such as penetration of the drug across skin layers at the tumor site and limited light penetrability. In this study, curcumin, an active anti-cancer agent, and chlorin e6, a photoactivable molecule, were encapsulated into lipidic nanoparticles that produced reactive oxygen species (ROS) when activated at 665 nm by near-infrared (NIR) light. The optimized lipidic nanoparticle containing curcumin and chlorin e6 exhibited a particle size of less than 100 nm. The entrapment efficiency for both molecules was found to be 81%. The therapeutic efficacy of the developed formulation was tested on B16F10 and A431 cell lines via cytotoxicity evaluation, combination index, cellular uptake, nuclear staining, DNA fragmentation, ROS generation, apoptosis, and cell cycle assays under NIR irradiation (665 nm). Co-delivering curcumin and chlorin e6 exhibited higher cellular uptake, better cancer growth inhibition, and pronounced apoptotic events compared to the formulation having the free drug alone. The study results depicted that topical application of this ROS-generating dual-drug-loaded lipidic nanoparticles incorporated in SEPINEO gel achieved better permeation (80 ± 2.45%) across the skin, and exhibited the improved skin retention and a synergistic effect as well. The present work introduces photo-triggered ROS-generating dual-drug-based lipidic nanoparticles, which are simple and efficient to develop and exhibit synergistic therapeutic effects against cutaneous melanoma.


Subject(s)
Curcumin , Melanoma , Nanoparticles , Photochemotherapy , Skin Neoplasms , Humans , Melanoma/drug therapy , Skin Neoplasms/drug therapy , Reactive Oxygen Species/metabolism , Nanoparticles/therapeutic use , Lipids , Cell Line, Tumor , Melanoma, Cutaneous Malignant
6.
J Drug Target ; 31(5): 486-499, 2023 06.
Article in English | MEDLINE | ID: mdl-37125741

ABSTRACT

With the advancement of nanotechnology, many different forms of nanoparticles (NPs) are created, which specifically enhance anticancer drug delivery to tumour cells. Albumin bio-macromolecule is a flexible protein carrier for the delivery of drugs that is biodegradable, biocompatible, and non-toxic. As a result, it presents itself as an ideal material for developing nanoparticles for anticancer drug delivery. Toxicological investigations demonstrated that this novel drug delivery technique is safe for use in the human population. Furthermore, drug compatibility with the albumin nanoparticle is remarkable. The robust structure of the nanoparticle, high drug encapsulation, and customisable drug release make it a promising carrier option for the treatment of lung cancer. In this review, we summarise human serum albumin and bovine serum albumin in the targeted delivery of anticancer drugs to lung cancer cells.


Subject(s)
Antineoplastic Agents , Carcinoma , Lung Neoplasms , Nanoparticles , Humans , Drug Carriers/chemistry , Nanoparticles/chemistry , Drug Delivery Systems/methods , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/chemistry , Serum Albumin, Bovine/chemistry , Lung Neoplasms/drug therapy , Lung , Particle Size
7.
Pharmaceutics ; 15(3)2023 Feb 22.
Article in English | MEDLINE | ID: mdl-36986597

ABSTRACT

The current study aimed to develop a topical emulgel of dasatinib (DTB) for rheumatoid arthritis (RA) treatment to reduce systemic side effects. The quality by design (QbD) approach was employed to optimize DTB-loaded nano-emulgel using a central composite design (CCD). Emulgel was prepared using the hot emulsification method, and then the particle size (PS) was reduced using the homogenization technique. The PS and % entrapment efficiency (% EE) were found to be 172.53 ± 3.33 nm (0.160 ± 0.014 PDI) and 95.11 ± 0.16%, respectively. The nano-emulsion (CF018 emulsion) in vitro drug release profile showed sustained release (SR) up to 24 h. MTT assay results from an in vitro cell line study revealed that formulation excipients had no effect, whereas emulgel showed a high degree of internalization. Furthermore, emulgel treatment significantly reduced LPS-induced TNF-α production in RAW 264.7 cells. The spherical shape was depicted in FESEM images of optimized nano-emulgel (CF018 emulgel) formulation. Ex vivo skin permeation was significantly increased when compared to the free drug-loaded gel (FDG). In vivo data revealed that the optimized CF018 emulgel is a non-irritant and is safe. In terms of paw swelling, the FCA-induced arthritis model demonstrated that the CF018 emulgel reduced paw swelling percentage compared to adjuvant-induced arthritis (AIA) control group. Following clinical testing in the near future, the designed preparation could be a viable alternative treatment for RA.

8.
Inflammopharmacology ; 31(2): 699-716, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36952096

ABSTRACT

In metabolic syndrome, dysregulated signalling activity of the insulin receptor pathway in the brain due to persistent insulin resistance (IR) condition in the periphery may lead to brain IR (BIR) development. BIR causes an upsurge in the activity of glycogen synthase kinase-3 beta, increased amyloid beta (Aß) accumulation, hyperphosphorylation of tau, aggravated formation of Aß oligomers and simultaneously neurofibrillary tangle formation, all of which are believed to be direct contributors in Alzheimer's Disease (AD) pathology. Likewise, for Parkinson's Disease (PD), BIR is associated with alpha-synuclein alterations, dopamine loss in brain areas which ultimately succumbs towards the appearance of classical motor symptoms corresponding to the typical PD phenotype. Modulation of the autophagy process for clearing misfolded proteins and alteration in histone proteins to alleviate disease progression in BIR-linked AD and PD have recently evolved as a research hotspot, as the majority of the autophagy-related proteins are believed to be regulated by histone posttranslational modifications. Hence, this review will provide a timely update on the possible mechanism(s) converging towards BIR induce AD and PD. Further, emphasis on the potential epigenetic regulation of autophagy that can be effectively targeted for devising a complete therapeutic cure for BIR-induced AD and PD will also be reviewed.


Subject(s)
Alzheimer Disease , Insulin Resistance , Parkinson Disease , Humans , Alzheimer Disease/metabolism , Parkinson Disease/drug therapy , Amyloid beta-Peptides/metabolism , Insulin Resistance/physiology , Epigenesis, Genetic , Histones/genetics , Histones/metabolism , Histones/therapeutic use , Brain/metabolism , Autophagy
9.
ACS Chem Neurosci ; 14(4): 590-602, 2023 02 15.
Article in English | MEDLINE | ID: mdl-36724408

ABSTRACT

Parkinson's disease is the second most prevalent neurological disease after Alzheimer's. Primarily, old age males are more affected than females. The aggregates of oligomeric forms of α-synuclein cause the loss of dopaminergic neurons in the substantia nigra pars compacta. Further, it leads to dopamine shortage in the striatum region. According to recent preclinical studies, environmental factors like pesticides, food supplements, pathogens, etc. enter the body through the mouth or nose and ultimately reach the gut. Further, these factors get accumulated in enteric nervous system which leads to misfolding of α-synuclein gene, and aggregation of this gene results in Lewy pathology in the gut and reaches to the brain through the vagus nerve. This evidence showed a strong bidirectional connection between the gut and the brain, which leads to gastrointestinal problems in Parkinson patients. Moreover, several studies reveal that patients with Parkinson experience more gastrointestinal issues in the early stages of the disease, such as constipation, increased motility, gut inflammation, etc. This review article focuses on the transmission of α-synuclein and the mechanisms involved in the link between the gut and the brain in Parkinson's disease. Also, this review explores the various pathways involved in Parkinson and current therapeutic approaches for the improvement of Parkinson's disease.


Subject(s)
Parkinson Disease , Female , Humans , Male , alpha-Synuclein/metabolism , Brain/metabolism , Dopaminergic Neurons/metabolism , Parkinson Disease/metabolism , Vagus Nerve/metabolism , Brain-Gut Axis
10.
Pharmaceutics ; 15(1)2023 Jan 03.
Article in English | MEDLINE | ID: mdl-36678794

ABSTRACT

Nano-emulgel is an emerging drug delivery system intended to enhance the therapeutic profile of lipophilic drugs. Lipophilic formulations have a variety of limitations, which includes poor solubility, unpredictable absorption, and low oral bioavailability. Nano-emulgel, an amalgamated preparation of different systems aims to deal with these limitations. The novel system prepared by the incorporation of nano-emulsion into gel improves stability and enables drug delivery for both immediate and controlled release. The focus on nano-emulgel has also increased due to its ability to achieve targeted delivery, ease of application, absence of gastrointestinal degradation or the first pass metabolism, and safety profile. This review focuses on the formulation components of nano-emulgel for topical drug delivery, pharmacokinetics and safety profiles.

11.
Pharmaceutics ; 15(1)2023 Jan 11.
Article in English | MEDLINE | ID: mdl-36678877

ABSTRACT

Triple-negative breast cancer (TNBC) is a life-threatening form of breast cancer which has been found to account for 15% of all the subtypes of breast cancer. Currently available treatments are significantly less effective in TNBC management because of several factors such as poor bioavailability, low specificity, multidrug resistance, poor cellular uptake, and unwanted side effects being the major ones. As a rapidly growing field, nano-therapeutics offers promising alternatives for breast cancer treatment. This platform provides a suitable pathway for crossing biological barriers and allowing sustained systemic circulation time and an improved pharmacokinetic profile of the drug. Apart from this, it also provides an optimized target-specific drug delivery system and improves drug accumulation in tumor cells. This review provides insights into the molecular mechanisms associated with the pathogenesis of TNBC, along with summarizing the conventional therapy and recent advances of different nano-carriers for the management of TNBC.

12.
J Control Release ; 354: 794-809, 2023 02.
Article in English | MEDLINE | ID: mdl-36709923

ABSTRACT

Understanding and establishing a link between the physicochemical characteristics of nanoparticles (NPs) and their biological interactions poses to be a great challenge in the field of nanotherapeutics. Recent analytical advancements concerning bio-nanointerfaces have accelerated the quest to comprehend the fate of nanocarrier systems in vivo. Scientists have discovered that protein corona, an adsorbed layer of biomolecules on the surface of NPs takes a leading part in interacting with cells and in the cellular uptake process, thereby determining the in vivo behaviour of NPs. Another useful method to assess the in vivo fate of NPs is by performing dissolution testing. This forms the basis for in vitro in vivo correlation (IVIVC), relating in vitro dissolution of NPs and their in vivo properties. Scientists are continuously directing their efforts towards establishing IVIVC for different nanocarrier systems while concurrently gaining insights into protein corona. This review primarily summarizes the importance of protein corona and its interaction with nanoparticles. It also gives an insight into the factors affecting the interaction and various in vitro dissolution media used for varied nanocarrier systems. The article concludes with a discussion of the limitations of IVIVC modelling and its position from a regulatory perspective.


Subject(s)
Nanoparticles , Protein Corona , Protein Corona/metabolism , Nanoparticles/chemistry
13.
ACS Chem Neurosci ; 14(4): 725-740, 2023 02 15.
Article in English | MEDLINE | ID: mdl-36694924

ABSTRACT

Imbalance in brain glucose metabolism and epigenetic modulation during the disease course of insulin resistance (IR) associated with Parkinson's disease (PD) risk remains a prime concern. Fibroblast growth factor 21 (FGF21), the metabolic hormone, improves insulin sensitivity and elicits anti-diabetic properties. Chronic stress during brain IR may modulate the FGF21 expression and its dynamic release via epigenetic modifications. Metformin regulates and increases the expression of FGF21 which can be modulating in obesity, diabetes, and IR. Hence, this study was designed to investigate the FGF21 expression modulation via an epigenetic mechanism in PD and whether metformin (MF), an autophagy activator, and sodium butyrate (NaB), a pan histone deacetylase inhibitor, alone and in combination, exert any therapeutic benefit in PD pathology exacerbated by high-fat diet (HFD). Our results portray that the combination treatment with MF and NaB potentially attenuated the abnormal lipid profile and increased motor performance for the rats fed with HFD for 8 weeks followed by intrastriatal 6-hydroxy dopamine administration. The enzyme-linked immunosorbent assay (ELISA) estimations of C-reactive protein, tumor necrosis factor-α, interleukin-1 beta and 6, and FGF21 exhibited extensive downregulation after treatment with the combination. Lastly, mRNA, western blot, histological, and cresyl violet staining depicted that the combination treatment can restore degenerated neuronal density and increase the protein level compared to the disease group. The findings from the study effectively conclude that the epigenetic mechanism involved in FGF21 mediated functional abnormalities in IR-linked PD pathology. Hence, combined treatment with MF and NaB may prove to be a novel combination in ameliorating IR-associated PD in rats, probably via the upregulation of FGF21 expression.


Subject(s)
Insulin Resistance , Metformin , Parkinson Disease , Animals , Rats , Diet, High-Fat , Epigenesis, Genetic , Metformin/pharmacology , Parkinson Disease/drug therapy
14.
Environ Monit Assess ; 195(1): 51, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36316588

ABSTRACT

Wheat is the important food grain and is cultivated in many Indian states: Punjab, Haryana, Uttar Pradesh, and Madhya Pradesh, which contributes to major crop production in India. In this study, popular statistical approach multiple linear regression (MLR) and time series approaches Time Delay Neural Network (TDNN) and ARIMAX models were envisaged for wheat yield forecast using weather parameters for a case study area, i.e., Junagarh district, western Gujarat region situated at the foot of Mount Girnar. Weather data corresponds to 19 weeks (42nd to 8th Standard Meteorological Week, SMW) during crop growing season was used for prediction of wheat yield using these statistical techniques and were evaluated for their predictive capability. Furthermore, trend analysis among weather parameters and crop yield was also carried out in this study using non-parametric Mann-Kendall test and Sen's slope method. Significant negative correlation was observed between wheat yield and some of the weekly weather variables, viz., maximum temperature (48, 49, 50, 51, 52, and 4th SMW), and total rainfall (50, 51, and 1st SMW) while positive correlation was observed with morning relative humidity (49 and 3rd SMW). Study indicated that forecast error varied from 1.80 to 10.28 in MLR, 0.79 to 7.79 in ARIMAX (2,2,2), - 3.09 to 10.18 in TDNN (4,5) during model training period (1985-2014). The MAPE value shows that the time series data predicted less than 5% of variation, whereas the conventional MLR technique indicated more than 7% variation. Both ARIMAX and TDNN approaches indicated better performance during model training periods, i.e., 1985-2014 and 1985-2015, while former performed well during the forecast periods 1985-2016 and 1985-2017. Overall, the study indicated that the ARIMAX approach can be used consistently for 4 years using the same model.


Subject(s)
Agriculture , Environmental Monitoring , Triticum , Edible Grain/growth & development , Seasons , Triticum/growth & development , Weather , India , Forecasting
15.
AAPS PharmSciTech ; 23(7): 254, 2022 Sep 15.
Article in English | MEDLINE | ID: mdl-36109473

ABSTRACT

Sorafenib tosylate (SFNT) is the first-line drug for hepatocellular carcinoma. It exhibits poor solubility leading to low oral bioavailability subsequently requiring intake of large quantities of drug to exhibit desired efficacy. The present investigation was aimed at enhancing the solubility and dissolution rate of SFNT using complexation method. The binary inclusion complex was prepared with ß-cyclodextrin (ß-CD). The molecular docking studies confirmed the hosting of SFNT into hydrophobic cavity of ß-CD, while the phase solubility studies revealed the stoichiometry of complexation with a stability constant of 735.8 M-1. The ternary complex was prepared by combining the SFNT-ß-CD complex with PEG-6000 and HPMC polymers. The results from ATR-IR studies revealed no interaction between drug and excipients. The decreased intensities in ATR-IR peaks and changes in chemical shifts from NMR of SFNT in complexes indicate the possibility of SFNT hosting into the hydrophobic cavity of ß-CD. The disappearance of SFNT peak in DSC and XRD studies revealed the amorphization upon complexation. The ternary complexes exhibited improved in vitro solubility (17.54 µg/mL) compared to pure SFNT (0.19 µg/mL) and binary inclusion complex (1.52 µg/mL). The dissolution profile of ternary inclusion complex in 0.1 N HCl was significantly higher compared to binary inclusion complex and pure drug. In cytotoxicity studies, the ternary inclusion complex has shown remarkable effect than the binary inclusion complex and pure drug on HepG2 cell lines.


Subject(s)
Polymers , beta-Cyclodextrins , Excipients , Molecular Docking Simulation , Sorafenib , Ternary Complex Factors , beta-Cyclodextrins/chemistry
16.
Article in English | MEDLINE | ID: mdl-36159728

ABSTRACT

Photodynamic therapy (PDT), as the name suggests is a light-based, non-invasive therapeutic treatment method that has garnered immense interest in the recent past for its efficacy in treating several pathological conditions. PDT has prominent use in the treatment of several dermatological conditions, which consequently have cosmetic benefits associated with it as PDT improves the overall appearance of the affected area. PDT is commonly used for repairing sun-damaged skin, providing skin rejuvenation, curbing pre-cancerous cells, treating conditions like acne, keratosis, skin-microbial infections, and cutaneous warts, etc. PDT mediates its action by generating oxygen species that are involved in bringing about immunomodulation, suppression of microbial load, wound-healing, lightening of scarring, etc. Although there are several challenges associated with PDT, the prominent ones being pain, erythema, insufficient delivery of the photosensitizing agent, and poor clinical outcomes, still PDT stands to be a promising approach with continuous efforts towards maximizing clinical efficacy while being cautious of the side effects and working towards lessening them. This article discusses the major skin-related conditions which can be treated or managed by employing PDT as a better or comparable alternative to conventional treatment approaches such that it also brings about aesthetic improvements thereof.

17.
Photodiagnosis Photodyn Ther ; 40: 103091, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36031144

ABSTRACT

Photodynamic therapy (PDT) is highly efficient in eradicating targetlesions by using photosensitizers (PS) triggered by external light energy. Nanotechnology may help increase the solubility and effective delivery of PS towards improving its efficacy. Curcumin (Cur) was used as a natural PS for PDT in the present work. Briefly, curcumin was encapsulated in liposomes (LPs) using the thin film hydration method and optimized using the QbD approach through the Box-Behnken Design (BBD) to optimize the responses like entrapment efficiency and drug loading with a smaller vesicle size. The in vitro release studies performed using a dialysis bag (MWCO 12 KDa) suggested a sustained release of the Cur over 72 h in pH 7.4 PBS following the Weibull drug release kinetics. In addition, the ROS generating capabilities upon application of blue light (460 nm) and resulting cytotoxicity were evaluated in MCF-7 cell lines. The Cur-loaded liposome exhibited significant ROS generation and cytotoxicity to the cancer cells than free curcumin. Thus, the Cur-loaded liposomes could be used to treat breast cancer with photodynamic therapy.


Subject(s)
Curcumin , Photochemotherapy , Humans , MCF-7 Cells , Photochemotherapy/methods , Curcumin/therapeutic use , Drug Liberation , Liposomes , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic use , Particle Size
18.
Curr Drug Targets ; 23(10): 978-1001, 2022.
Article in English | MEDLINE | ID: mdl-35657283

ABSTRACT

Alzheimer's disease (AD) is a multifactorial, progressive, neurodegenerative disorder, manifested by the loss of memory and cognitive abilities, behavioral disturbance and progressive impairment of activities of daily life. The sharp rise in the number of AD patients has brought it within the top eight health issues in the world. It is associated with the distribution of misfolded aggregates of protein within the brain. However, Alois Alzheimer initially mentioned that the reduction in brain volume in AD might be associated with the "deposition of a special substance in the cortex". The resulting plaque found in extracellular space in the AD brain and hippocampus region, known as senile plaques, is the characteristic feature underlying Alzheimer's pathology, where the role of amyloid- ß (Aß) peptide formation from proteolytic cleavage of amyloid precursor protein (APP) by secretase enzyme is eminent. Therefore, this review has highlighted the molecular pathophysiology of AD with a variety of available diagnostic and treatment strategies for the management of the disease, with a focus on the advancement toward clinical research to provide new effective and safe tool in the diagnosis, treatment or management of AD.


Subject(s)
Alzheimer Disease , Amyloid Precursor Protein Secretases , Amyloid beta-Peptides , Disease Progression , Humans , Plaque, Amyloid
19.
Microbiol Spectr ; 10(3): e0059522, 2022 06 29.
Article in English | MEDLINE | ID: mdl-35435754

ABSTRACT

Chikungunya virus (CHIKV) is a reemerging alphavirus causing chikungunya disease (CHIKD) and is transmitted to humans by Aedes mosquitoes. The virus establishes an intricate balance of cellular interactions that ultimately helps in its replication and dodges cellular immune response. In an attempt to identify cellular host factors required during CHIKV replication in Aag2 cells, we performed global transcriptomics of CHIKV-infected Aag2 cells, and further, we compared this library with the Drosophila RNAi Screening Center (DRSC) database and identified transcripts that were regulated in Aedes aegypti during CHIKV infection. These analyses revealed specific pathways, such as ubiquitin-related pathways, proteolysis pathways, protein catabolic processes, protein modification, and cellular protein metabolic processes, involved during replication of the virus. Loss-of-function assays of selected candidates revealed their proviral or antiviral characteristics upon CHIKV infection in A. aegypti-derived Aag2 cells. Further validations identified that the ubiquitin proteasomal pathway is required for CHIKV infection in A. aegypti and that an important member of this family of proteins, namely, AeCullin-3 (Aedes ortholog of human cullin-3), is a proviral host factor of CHIKV replication in Aag2 cells. IMPORTANCE Arboviruses cause several diseases in humans and livestock. Vector control is the main strategy for controlling diseases transmitted by mosquitoes. In this context, it becomes paramount to understand how the viruses replicate in the vector for designing better transmission blocking strategies. We obtained the global transcriptome signature of A. aegypti cells during CHIKV infection, and in order to obtain the maximum information from these data sets, we further utilized the well-characterized Drosophila system and arrived upon a set of transcripts and their pathways that affect A. aegypti cells during CHIKV infection. These analyses and further validations reveal that important pathways related to protein degradation are actively involved during CHIKV infection in A. aegypti and are mainly proviral. Targeting these molecules may provide novel approaches for blocking CHIKV replication in A. aegypti.


Subject(s)
Aedes , Chikungunya Fever , Chikungunya virus , Animals , Chikungunya virus/genetics , Drosophila , Mosquito Vectors , Proviruses , Ubiquitin-Protein Ligases , Ubiquitins
20.
J Biomater Sci Polym Ed ; 33(12): 1531-1554, 2022 08.
Article in English | MEDLINE | ID: mdl-35404217

ABSTRACT

There has been a growing interest in the scientific community to explore the complete potential of phytoconstituents, herbal or plant-based ingredients owing to a range of benefits they bring along. The herbal plants accommodate many phytoconstituents that are responsible for various activities such as anti-oxidant, antimicrobial, anticancer, anti-inflammatory, anti-allergic, hepatoprotective, etc. However, these phytoconstituents are highly sensitive to several environmental and physiological factors such as pH, oxygen, heat, temperature, humidity, stomach acid, enzymes, and light. Hence, there is need for the development of a drug delivery system that can protect the phytoconstituents from both internal and external conditions. In this regard, a microparticulate drug delivery system is considered amongst the ideal choice owing to its small size, ability to protect the environment-sensitive active constituents, in achieving sustained drug delivery, targeted drug delivery, protection of the drug from physiological conditions, minimizing drug-related side effects, etc.


Subject(s)
Anti-Infective Agents , Drug Delivery Systems , Anti-Inflammatory Agents/therapeutic use , Nanotechnology , Plant Extracts
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