ABSTRACT
The objective of the research was to identify significant variables that impact the porosity-related properties of CaCO3 particles. The Placket-Burman design was employed to screen multiple variables, including pH, molar concentrations of calcium chloride and sodium carbonate, temperature, concentration of Gelucire 44/14, Cremophor RH40, Solutol HS15, Labrasol, mixing rate, reaction time, and order of addition. The response variables were surface area, pore radius, and pore volume. Influential methodologies such as XRD, FTIR, Raman spectroscopy, and TGA were utilized to validate the precipitate type. The BET surface area ranged from 1.5 to 16.14 m2/g, while the pore radius varied from 2.62 to 6.68 nm, and the pore volume exhibited a range of 2.43 to 37.97 cc/gm. Vaterite structures with spherical mesoporous characteristics were observed at high pH, whereas calcite formations occurred at low pH. The order of addition impacted the surface area but did not affect the pore volume. To maximize the surface area, a lower reaction time and molar concentrations of sodium carbonate were found to be advantageous. The pore radius was influenced by the pH, surfactants, and reaction conditions. The sediments were categorized based on the percentage of vaterite formation. The instrumental techniques effectively characterized the precipitates and provided a valuable complementary analysis.
ABSTRACT
The use of amphiphilic block copolymers to generate colloidal delivery systems for hydrophobic drugs has been the subject of extensive research, with several formulations reaching the clinical development stages. However, to generate particles of uniform size and morphology, with high encapsulation efficiency, yield and batch-to-batch reproducibility remains a challenge, and various microfluidic technologies have been explored to tackle these issues. Herein, we report the development and optimization of poly(ethylene glycol)-block-(ε-caprolactone) (PEG-b-PCL) nanoparticles for intravenous delivery of a model drug, sorafenib. We developed and optimized a glass capillary microfluidic nanoprecipitation process and studied systematically the effects of formulation and process parameters, including different purification techniques, on product quality and batch-to-batch variation. The optimized formulation delivered particles with a spherical morphology, small particle size (dH < 80 nm), uniform size distribution (PDI < 0.2), and high drug loading degree (16 %) at 54 % encapsulation efficiency. Furthermore, the stability and in vitro drug release were evaluated, showing that sorafenib was released from the NPs in a sustained manner over several days. Overall, the study demonstrates a microfluidic approach to produce sorafenib-loaded PEG-b-PCL NPs and provides important insight into the effects of nanoprecipitation parameters and downstream processing on product quality.
Subject(s)
Nanoparticles , Neoplasms , Humans , Sorafenib , Drug Carriers/chemistry , Microfluidics , Reproducibility of Results , Polyesters/chemistry , Polyethylene Glycols/chemistry , Nanoparticles/chemistry , Particle SizeABSTRACT
Recent mounting evidence has revealed extensive genetic heterogeneity within tumors that drive phenotypic variation affecting key cancer pathways, making cancer treatment extremely challenging. Diverse cancer types display resistance to treatment and show patterns of relapse following therapy. Therefore, efforts are required to address tumor heterogeneity by developing a broad-spectrum therapeutic approach that combines targeted therapies. Inflammation has been progressively documented as a vital factor in tumor advancement and has consequences in epigenetic variations that support tumor instigation, encouraging all the tumorigenesis phases. Increased DNA damage, disrupted DNA repair mechanisms, cellular proliferation, apoptosis, angiogenesis, and its incursion are a few pro-cancerous outcomes of chronic inflammation. A clear understanding of the cellular and molecular signaling mechanisms of tumor-endorsing inflammation is necessary for further expansion of anti-cancer therapeutics targeting the crosstalk between tumor development and inflammatory processes. Multiple inflammatory signaling pathways, such as the NF-κB signaling pathway, JAK-STAT signaling pathway, MAPK signaling, PI3K/AKT/mTOR signaling, Wnt signaling cascade, and TGF-ß/Smad signaling, have been found to regulate inflammation, which can be modulated using various factors such as small molecule inhibitors, phytochemicals, recombinant cytokines, and nanoparticles (NPs) in conjugation to phytochemicals to treat cancer. Researchers have identified multiple targets to specifically alter inflammation in cancer therapy to restrict malignant progression and improve the efficacy of cancer therapy. siRNA-and shRNA-loaded NPs have been observed to downregulate STAT3 signaling pathways and have been employed in studies to target tumor malignancies. This review highlights the pathways involved in the interaction between tumor advancement and inflammatory progression, along with the novel approaches of nanotechnology-based drug delivery systems currently used to target inflammatory signaling pathways to combat cancer.
Subject(s)
Nanomedicine , Phosphatidylinositol 3-Kinases , Humans , Phosphatidylinositol 3-Kinases/metabolism , Comprehension , Neoplasm Recurrence, Local , Signal Transduction , Inflammation/drug therapyABSTRACT
The presence of small subpopulations of cells within tumor cells are known as cancer stem cells (CSCs). These cells have been the reason for metastasis, resistance with chemotherapy or radiotherapy, and tumor relapse in several types of cancers. CSCs underwent to epithelial-mesenchymal transition (EMT) and resulted in the development of aggressive tumors. CSCs have potential to modulate numerous signaling pathways including Wnt, Hh, and Notch, therefore increasing the stem-like characteristics of cancer cells. The raised expression of drug efflux pump and suppression of apoptosis has shown increased resistance with anti-cancer drugs. Among many agents which were shown to modulate these, the plant-derived bioactive agents appear to modulate these key regulators and were shown to remove CSCs. This review aims to comprehensively scrutinize the preclinical and clinical studies demonstrating the effects of phytocompounds on CSCs isolated from various tumors. Based on the available convincing literature from preclinical studies, with some clinical data, it is apparent that selective targeting of CSCs with plants, plant preparations, and plant-derived bioactive compounds, termed phytochemicals, may be a promising strategy for the treatment of relapsed cancers.
ABSTRACT
Doxorubicin (DOX)-loaded lysolipid temperature-sensitive liposomes (LTSLs) are a promising stimuli-responsive drug delivery system that rapidly releases DOX in response to mild hyperthermia (HT). This study investigates the influence of loaded DOX crystals on the thermosensitivity of LTSLs and their therapeutic efficacy in vitro and in vivo. The properties of DOX crystals were manipulated using different remote loading methods (namely (NH4)2SO4, NH4-EDTA and MnSO4) and varying the lipid:DOX weight ratio during the loading step. Our results demonstrated that (NH4)2SO4 or NH4-EDTA remote loading methods had a comparable encapsulation efficiency (EE%) into LTSLs in contrast to the low DOX EE% obtained using the metal complexation method. Cryogenic transmission electron microscopy (cryo-TEM) revealed key differences in the nature of DOX crystals formed inside LTSLs based on the loading buffer or/and the lipid:DOX ratio used, resulting in different DOX release profiles in response to mild HT. The in vitro assessment of DOX release/uptake in CT26 and PC-3 cells revealed that the use of a high lipid:DOX ratio exhibited a fast and controlled release profile in combination with mild HT, which correlated well with their cytotoxicity studies. Similarly, in vivo DOX release, tumour growth inhibition and mice survival rates were influenced by the physicochemical properties of LTSLs payload. This study demonstrates, for the first time, that the characteristics of DOX crystals loaded into LTSLs, and their conformational rearrangement during HT, are important factors that impact the TSLs performance in vivo.
Subject(s)
Hyperthermia, Induced , Liposomes , Animals , Antibiotics, Antineoplastic , Cell Line, Tumor , Doxorubicin , Mice , TemperatureABSTRACT
The self-assembly of phospholipids in oil, specifically lecithin in rapeseed oil, was investigated by combining experimental and computational methods The influence of temperature, water, and free fatty acids on the onset of lecithin aggregation in the rapeseed oil was determined using the 7,7,8,8 -tetracyanoquinodimethane dye (TCNQ) solubilization method and the size and shape of the self-assembled lecithin structures were investigated by small-angle X-ray scattering and cryogenic transmission electron microscopy. In the absence of excess water in the system (0.03wt-% water in oil), stable cylindrical lecithin reverse micelles were observed above the critical micelle concentration (CMC). Comparing the aggregation response in room temperature and at 70°C revealed that CMC decreased with increasing temperature. Furthermore, already a modest amount of added water (0.3wt-% water in oil) was sufficient to induce the formation of lamellar lecithin structures, that phase separated from the oil. In low water content, oleic acid suppressed the formation of lecithin reverse micelles whereas in the presence of more water, the oleic acid stabilized the reverse micelles. Consequently, more water was needed to induce phase separation in the presence of oleic acid. Molecular dynamics simulations indicated that the stabilizing effect of oleic acid resulted from oleic acid enhancing phospholipid solubilization in the oil by forming a solvating shell around the phosphate head group. The findings showed that the response of the mixed surfactant system is a delicate interplay of the different components and variables. The significance of the observations is that multiple parameters need to be controlled for desired system response, for example towards vegetable oil purification or phospholipid based microemulsions.