The contribution of the complement system to non-specific host defence and maintenance of homeostasis is well appreciated. Many particulate systems trigger complement activation but the underlying ...mechanisms are still poorly understood. Activation of the complement cascade could lead to particle opsonisation by the cleavage products of the third complement protein and might promote inflammatory reactions. Antibody binding in a controlled manner and/or sensing of particles by the complement pattern-recognition molecules such as C1q and mannose-binding lectin can trigger complement activation. Particle curvature and spacing arrangement/periodicity of surface functional groups/ligands are two important parameters that modulate complement responses through multivalent engagement with and conformational regulation of surface-bound antibodies and complement pattern-recognition molecules. Thus, a better fundamental understanding of nanometer- and angstrom-scale parameters that modulate particle interaction with antibodies and complement proteins could portend new possibilities for engineering of particulate drug carriers and biomedical platforms with tuneable complement responses and is discussed here.
Display omitted
•Many nano−/micro-particles trigger complement activation in human plasma.•Particle curvature modulates complement responses.•Spacing arrangement/periodicity of surface moieties modulates complement responses.•Refinement of particle size and surface properties overcomes complement activation.
The complement system, professional phagocytes and other cells such as Natural killer cells and mast cells are among the important components of the innate arm of the immune system. These ...constituents provide an orchestrated array of defences and responses against tissue injury and foreign particles, including nanopharmaceuticals. While interception of nanopharmaceuticals by the immune system is beneficial for immunomodulation and treatment of phagocytic cell disorders, it is imperative to understand the multifaceted mechanisms by which nanopharmaceuticals interacts with the immune system and evaluate the subsequent balance of beneficial versus adverse reactions. An example of the latter is adverse infusion reactions to regulatory-approved nanopharmaceuticals seen in human subjects. Here, we discuss collective opinions and findings from our laboratories in mapping nanoparticle-mediated complement and leucocyte/macrophage responses.
Display omitted
•Complement system plays multifaceted roles in nanoparticle performance.•Phagocytic cells intercepts nanoparticles in multiple ways.•The role of phagocytes, complement and contact system in hypersensitivity to nanoparticles is scrutinised.
The complement system is a multicomponent and multifunctional arm of the innate immune system. Complement contributes to non-specific host defence and maintains homeostasis through multifaceted ...processes and pathways, including crosstalk with the adaptive immune system, the contact (coagulation) and the kinin systems, and alarmin high-mobility group box 1. Complement is also present intracellularly, orchestrating a wide range of housekeeping and physiological processes in both immune and nonimmune cells, thus showing its more sophisticated roles beyond innate immunity, but its roles are still controversial. Particulate drug carriers and nanopharmaceuticals typically present architectures and surface patterns that trigger complement system in different ways, resulting in both beneficial and adverse responses depending on the extent of complement activation and regulation as well as pathophysiological circumstances. Here we consider the role of complement system and complement regulations in host defence and evaluate the mechanisms by which nanoparticles trigger and modulate complement responses. Effective strategies for the prevention of nanoparticle-mediated complement activation are introduced and discussed.
Biodegradable poly(alkyl cyanoacrylate) (PACA) nanoparticles (NPs) are receiving increasing attention in anti-cancer nanomedicine development not only for targeted cancer chemotherapy, but also for ...modulation of the tumor microenvironment. We previously reported promising results with cabazitaxel (CBZ) loaded poly(2-ethylbutyl cyanoacrylate) NPs (PEBCA-CBZ NPs) in a patient derived xenograft (PDX) model of triple-negative breast cancer, and this was associated with a decrease in M2 macrophages. The present study aims at comparing two endotoxin-free PACA NP variants (PEBCA and poly(2-ethylhexyl cyanoacrylate); PEHCA), loaded with CBZ and test whether conjugation with folate would improve their effect.
Cytotoxicity assays and cellular uptake of NPs by flow cytometry were performed in different breast cancer cells. Biodistribution and efficacy studies were performed in PDX models of breast cancer. Tumor associated immune cells were analyzed by multiparametric flow cytometry.
In vitro studies showed similar NP-induced cytotoxicity patterns despite difference in early NP internalization. On intravenous injection, the liver cleared the majority of NPs. Efficacy studies in the HBCx39 PDX model demonstrated an enhanced effect of drug-loaded PEBCA variants compared with free drug and PEHCA NPs. Furthermore, the folate conjugated PEBCA variant did not show any enhanced effects compared with the unconjugated counterpart which might be due to unfavorable orientation of folate on the NPs. Finally, analyses of the immune cell populations in tumors revealed that treatment with drug loaded PEBCA variants affected the myeloid cells, especially macrophages, contributing to an inflammatory, immune activated tumor microenvironment.
We report for the first time, comparative efficacy of PEBCA and PEHCA NP variants in triple negative breast cancer models and show that CBZ-loaded PEBCA NPs exhibit a combined effect on tumor cells and on the tumor associated myeloid compartment, which may boost the anti-tumor response.
Waste wood biomass as precursor for manufacturing activated carbon (AC) can provide a solution to ever increasing global water quality concerns. In our current work,
derived phosphoric acid-treated ...AC (MA-AC400) was manufactured at a laboratory scale. This novel MA-AC400 was tested for RO16 dye removal performance as a function of contact time, adsorbent dosage, pH, temperature and initial dye concentration in a batch scale arrangement. MA-AC400 was characterized via scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, dynamic light scattering (DLS) and fluorescence spectroscopy. MA-AC400 is characterized as mesoporous with BET surface area of 293.13 m
g
and average pore width of 20.33 Å. pH
and Boehm titration confirm the acidic surface charges with dominance of phenolic functional groups. The average DLS particle size of MA-AC400 was found in the narrow range of 0.12 to 0.30 µm and this polydispersity was confirmed with multiple excitation fluorescence wavelengths. MA-AC400 showed equilibrium adsorption efficiency of 97.8% for RO16 dye at its initial concentration of 30 mg L
and adsorbent dose of 1 g L
. Thermodynamic study endorsed the spontaneous, favorable, irreversible and exothermic process for RO16 adsorption onto MA-AC400. Equilibrium adsorption data was better explained by Langmuir with high goodness of fit (R
, 0.9964) and this fitness was endorsed with lower error functions. The kinetics data was found well fitted to pseudo-second order (PSO), and intra-particle diffusion kinetic models. Increasing diffusion constant values confirm the intraparticle diffusion at higher RO16 initial concentration and reverse was true for PSO chemisorption kinetics. MA-AC400 exhibited low desorption with studied eluents and its cost was calculated to be $8.36/kg.
Cr(VI) adsorption onto
Eucalyptus camaldulensis
sawdust (ECS) waste was investigated in batch and column reactors. Various parameters, including the adsorbent dose, pH, initial concentration, ...particle size, contact time and temperature were optimized. The maximum adsorption capacity (35.58mg g
-1
, 71.16%) was achieved at pH 2.0. Data fitted well to Freundlich and Halsey’s models (R
2
=0.992), indicating the multilayer adsorption of Cr(VI). It obeys the pseudo-second order kinetics. Endothermic and non-spontaneous nature of Cr(VI) adsorption was observed with positive values of changes in enthalpy (9.83 kJ mol
-1
), and Gibbs-free energy (1.52, 1.38, 1.24, 1.10 and 0.97 kJ mol
-1
), respectively. In this column study, the breakthrough curve time increased from 670 to 1,270min by increasing the bed height from 5 to 15 cm, respectively. Column data was found well fitted to bed depth service time model. Adsorption capacity at 60% breakthrough was 2,443.636mg L
-1
. The study indicates that ECS waste can be a promising adsorbent for Cr(VI) remediation from industrial effluents.
wood is made up of lignocellulosic material; this lignocellulosic material contains two types of biopolymers, i.e., carbohydrate and aromatic polymers. In this study, this lignocellulosic material ...was used to prepare biochar. Three biochar, i.e., laboratory-based (B1), barrel-based (B2), and brick kiln-biochar (B3), were used for fluoride and arsenic removal from aqueous solution. Barrel-based biochar was prepared by using the two-barrel method's alteration. The highest fluoride removal (99%) was attained at pH 2 in the presence of B1, while in the presence of B2 and B3, maximum fluoride removal was 90% and 45.7%, respectively. At pH 10, the maximum arsenic removal in the presence of B1, B2, and B3 was 96%, 94%, and 93%, respectively. The surface characteristics obtained by Fourier-transform infrared spectroscopy (FTIR) showed the presence of carbonyl group (C-O), and alkene (C=C) functional groups on all the three studied biochars. Isotherm studies showed that the adsorption was monolayered (all the adsorbed molecules were in contact with the surface layer of the adsorbent) as the Langmuir isotherm model best fits the obtained data. Adsorption kinetics was also performed. The R
value supports the pseudo-second-order kinetics, which means that chemisorption was involved in adsorbing fluoride and arsenic. It is concluded that B1 gives maximum removal for both fluoride (99%) and arsenic (96%). The study shows that lignocellulose-based biochar can be used for arsenic and fluoride removal from water.
Development of diabetic cataract is mainly associated with the accumulation of sorbitol via the polyol pathway through the action of Aldose reductase (AR). Hence, AR inhibitors are considered as ...potential agents in the management of diabetic cataract. This study explored the AR inhibition potential of
Hemidesmus indicus
var.
pubescens
root extract by in silico and ex vivo methods. Molecular docking studies (Auto Dock tool) between β-sitosterol, hemidesminine, hemidesmin-1, hemidesmin-2, and AR showed that β-sitosterol (− 10.2 kcal/mol) and hemidesmin-2 (− 8.07 kcal/mol) had the strongest affinity to AR enzyme. Ex vivo studies were performed by incubating isolated goat lenses in artificial aqueous humor using galactose (55 mM) as cataract inducing agent at room temperature (pH 7.8) for 72 h. After treatment with Vitamin E acetate − 100 µg/mL (standard) and test extract (500 and 1000 µg/mL) separately, the estimation of biochemical markers showed inhibition of lens AR activity and decreased sorbitol levels. Additionally, extract also normalized the levels of antioxidant markers like SOD, CAT, GSH. Our results showed evidence that
H. indicus
var.
pubescens
root was able to prevent cataract by prevention of opacification and formation of polyols that underlines its potential as a possible therapeutic agent against diabetic complications.
Graphic Abstract
Murva is an important drug in Ayurveda. Wattakaka volubilis is used as one of the botanical sources of Murva. The aim of this study is to evaluate the effect of the alcohol extract of W. volubilis ...root in streptoztocin (STZ) induced diabetes and diabetic neuropathy. Diabetes mellitus (DM) was induced by the administration of STZ (45 mg/kg, i.p). DM was induced within 72 h. Diabetic animals were treated with glimepiride (0.5 mg/kg) and ethyl alcohol extract 100 and 200 mg/kg for 21 d. After determining the changes in fasting serum glucose and lipid profile, animals were further treated for a period of 15 d to determine the protective effect of extract against diabetic neuropathy. All the alcohol extract treated animals, showed a significant decrease in serum glucose level (P<0.001), and overall decrease in the severity of diabetic neuropathy. Alcohol extract of W. volubilis root showed antihyperglycemic activity and beneficial protection against diabetic neuropathy and hence can be a promising agent for treatment and prevention of diabetic neuropathy.
Cr(VI) adsorption was studied for abundantly available low-cost lignocellulosic adsorbents in Pakistan namely, tobacco stalks (TS), white cedar stem (WCS) and eucalyptus bark (EB). Several process ...variables like contact time, adsorbent dose, pH, metal concentration, particle size and temperature were optimized in batch mode. EB showed high Cr(VI) adsorption of 63.66% followed by WCS 62% and TS 57% at pH 2, which is higher than most of the reported literature. Langmuir isotherm (R
= 0.999) was well fitted into the equilibrium Cr(VI) data of EB, suggesting homogeneous active sites and monolayer coverage of Cr(VI) onto the EB surface. Freundlich (R
= 0.9982) isotherm was better fitted to the equilibrium data of TS and WCS, revealing the adsorption sites with heterogeneous energy distribution and multilayer Cr(VI) adsorption. Moreover, the Cr(VI) adsorption of studied adsorbents followed the pseudo-second order kinetic model. Thermodynamic properties were investigated in two temperature ranges, i.e., T
(303–313 K) and T
(313–323 K). TS and EB showed the exothermic at T
and endothermic reactions at T
with entropy controlled adsorption at the solid-liquid interface, and WCS exhibited an opposite thermal trend with decreasing disorderness at solid-liquid interface as temperature rises. Gibbs free energy (ΔG>0) confirmed the non-spontaneous adsorption process for all studied adsorbents.
PDF
