Microplastics in landfill leachate: Occurrence, health concerns, and removal strategies.

Landfills are commonly used to manage solid waste, but they can contribute to microplastic (MPs) pollution. As plastic waste degrades in landfills, MPs are released into the surrounding environment, contaminating soil, groundwater, and surface water. This poses a threat to human health and the environment, as MPs can adsorb toxic substances. This paper provides a comprehensive review of the degradation process of macroplastics into microplastics, the types of MPs found in landfill leachate (LL), and the potential toxicity of microplastic pollution. The study also evaluates various physical-chemical and biological treatment methods for removing MPs from wastewater. The concentration of MPs in young landfills is higher than in old landfills, and specific polymers such as polypropylene, polystyrene, nylon, and polycarbonate contribute significantly to microplastic contamination. Primary treatments such as chemical precipitation and electrocoagulation can remove up to 60-99% of total MPs from wastewater, while tertiary treatments such as sand filtration, ultrafiltration, and reverse osmosis can remove up to 90-99%. Advanced techniques, such as a combination of membrane bioreactor, ultrafiltration, and nanofiltration (MBR + UF + NF), can achieve even higher removal rates. Overall, this paper highlights the importance of continuous monitoring of microplastic pollution and the need for effective microplastic removal from LL to protect human and environmental health. However, more research is needed to determine the actual cost and feasibility of these treatment processes at a larger scale.

Towards sustainable bioplastic production using the photoautotrophic bacterium Rhodopseudomonas palustris TIE-1.

Bacterial synthesis of polyhydroxybutyrates (PHBs) is a potential approach for producing biodegradable plastics. This study assessed the ability of Rhodopseudomonas palustris TIE-1 to produce PHBs under various conditions. We focused on photoautotrophy using a poised electrode (photoelectroautotrophy) or ferrous iron (photoferroautotrophy) as electron donors. Growth conditions were tested with either ammonium chloride or dinitrogen gas as the nitrogen source. Although TIE-1's capacity to produce PHBs varied fairly under different conditions, photoelectroautotrophy and photoferroautotrophy showed the highest PHB electron yield and the highest specific PHB productivity, respectively. Gene expression analysis showed that there was no differential expression in PHB biosynthesis genes. This suggests that the variations in PHB accumulation might be post-transcriptionally regulated. This is the first study to systematically quantify the amount of PHB produced by a microbe via photoelectroautotrophy and photoferroautotrophy. This work could lead to sustainable bioproduction using abundant resources such as light, electricity, iron, and carbon dioxide.

Surface-Modified Liposomal Formulation of Amphotericin B: In vitro Evaluation of Potential Against Visceral Leishmaniasis.

Surface modification of liposomes with targeting ligands is known to improve the efficacy with reduced untoward effects in treating infective diseases like visceral leishmaniasis (VL). In the present study, modified ligand (ML), designed by modifying polysaccharide with a long chain lipid was incorporated in liposomes with the objective to target amphotericin B (Amp B) to reticuloendothelial system and macrophages. Conventional liposomes (CL) and surface modified liposomes (SML) were characterized for size, shape, and entrapment efficiency (E.E.). Amp B SML with 3% w/w of ML retained the vesicular nature with particle size of ∼205 nm, E.E. of ∼95% and good stability. SML showed increased cellular uptake in RAW 264.7 cells which could be attributed to receptor-mediated endocytosis. Compared to Amp B solution, Amp B liposomes exhibited tenfold increased safety in vitro in RAW 264.7 and J774A.1 cell lines. Pharmacokinetics and biodistribution studies revealed high t 1/2, area under the curve (AUC)0-24, reduced clearance and prolonged retention in liver and spleen with Amp B SML compared to other formulations. In promastigote and amastigote models, Amp B SML showed enhanced performance with low 50% inhibitory concentration (IC50) compared to Amp B solution and Amp B CL. Thus, due to the targeting ability of ML, SML has the potential to achieve enhanced efficacy in treating VL.

Drug functionalized microbial polysaccharide based nanofibers as transdermal substitute.

In order to promote the natural healing process, drug-functionalized nanofibrous transdermal substitute was fabricated using gellan as chief polymer and polyvinyl alcohol (PVA) as supporting polymer via electrospinning technique. These fabricated nanofibers physiochemically mimic the extracellular matrix (ECM) which supports the cell growth. For neo-tissue regeneration in a sterilized environment, amoxicillin (Amx) was entrapped within these nanofibers. Entrapment of Amx in the nanofibers was confirmed by FESEM, FTIR, XRD and TG analysis. In vitro cell culture studies revealed that the fabricated non-cytotoxic nanofibers promoted enhance cell adherence and proliferation of human keratinocytes. A preliminary in vivo study performed on rat model for full thickness skin excision wound demonstrated the prompt re-epithelialization in early phase and quicker collagen deposition in later phases of wound healing in case of Amx-functionalized gellan/PVA nanofibers. Data collectively confirmed the potential usage of gellan based electrospun nanofibers as transdermal substitute for faster skin restoration.

Synthesis and Evaluation of Substituted Poly(organophosphazenes) as a Novel Nanocarrier System for Combined Antimalarial Therapy of Primaquine and Dihydroartemisinin.

PURPOSE: The synthesis and evaluation of novel biodegradable poly(organophosphazenes) (3-6) namely poly[bis-(2-propoxy)]phosphazene (3) poly[bis(4-acetamidophenoxy)]phosphazene (4)poly[bis(4-formylphenoxy)]phosphazene (5) poly[bis(4-ethoxycarbonylanilino)]phosphazene (6) bearing various hydrophilic and hydrophobic side groups for their application as nonocarrier system for antimalarial drug delivery is described. METHODS: The characterization of polymers was carried out by IR, (1)H-NMR and (31)P-NMR. The molecular weights of these novel polyphosphazenes were determined using size exclusion chromatography with a Waters 515 HPLC Pump and a Waters 2414 refractive index detector. The degradation behavior was studied by 200 mg pellets of polymers in phosphate buffers pH 5.5, 6.8 and 7.4 at 37°C. The degradation process was monitored by changes of mass as function of time and surface morphology of polymer pellets. The developed combined drugs nanoparticles formulations were evaluated for antimalarial potential in P. berghei infected mice. RESULTS: These polymers exhibited hydrolytic degradability, which can afford applications to a variety of drug delivery systems. On the basis of these results, the synthesized polymers were employed as nanocarriers for targeted drug delivery of primaquine and dihydroartemisinin. The promising in vitro release of both the drugs from nanoparticles formulations provided an alternative therapeutic combination therapy regimen for the treatment of drug resistant malaria. The nanoparticles formulations tested in resistant strain of P. berghei infected mice showed 100% antimalarial activity. CONCLUSIONS: The developed nanocarrier system provides an alternative combination regimen for the treatment of resistant malaria.

Potential of ionic liquids as emerging green solvent for the pretreatment of lignocellulosic biomass.

Lignocellulosic biomass is available in abundance as a renewable resource, but the major portion of it is often discarded as waste without utilizing its immense potential as an alternative renewable energy resource. To overcome recalcitrance of lignocellulosic biomass, various pretreatment methods are applied to it, so that the complex and rigid polymeric structure can be broken down into fractions susceptible for enzymatic hydrolysis. Effective and efficient biomass processing is the goal of pretreatment methods, but none of the explored pretreatment methods are versatile enough to fulfil the requirement of biomass processing with greater flexibility in terms of operational cost and desired output efficiency. Deployment of green solvents such as ionic liquids for the pretreatment of lignocellulosic biomass has been a topic of discussion amongst the scientific community in recent times. The presented work provides a detailed overview on the deployment of ionic liquid for the pretreatment of lignocellulosic biomass coupled with a brief discussion on other pretreatments methods. The recyclability and reusability along with other unique properties makes an ionic liquid pretreatment different from the other traditional pretreatment methods. Also, this study explores diverse critical parameters that governs the dissolution process of biomass. Hazardous properties of ionic liquids have also been explored. Future perspective and recommendations have been given for an efficient, effective, and eco-friendly deployment of ionic liquid in biomass pretreatment process.

Synthesis and characterizations of super adsorbent hydrogel based on biopolymer, Guar Gum-grafted-Poly (hydroxyethyl methacrylate) (Gg-g-Poly (HEMA)) for the removal of Bismarck brown Y dye from aqueous solution.

Chemical modification of guar gum was done by graft copolymerization of monomer hydroxyethyl methacrylate (HEMA) using azobisisobutyronitrile (AIBN) as initiator. Optimal reaction parameters were settled by varying one reaction condition and keeping the other constant. The optimum reaction conditions worked out were solvent system: binary, [H2O] = 15.00 mL, [acetone] = 5.00 mL, [HEMA] = 82.217× 10-2 mol/L, [AIBN] = 3.333 × 10-2 mol/L, reaction time = 3 h, reaction temperature = 60 °C on to 1.00 g guar gum with Pg = 1694.6 and %GE = 68,704.152. Pure guar gum polymer and grafts were analyzed by several physicochemical investigation techniques like FTIR, SEM, XRD, EDX, and swelling studies. Percent swelling of the guar gum polymer and grafts was investigated at pH 2.2, 7.0, 7.4 and 9.4 concerning time. The finest yield of Ps was recorded at pH 9.4 with time 24 h for graft copolymer. Guar gum and grafted samples were explored for the sorption of toxic dye Bismarck brown Y from the aqueous solution with respect to variable contact time, pH, temperature and dye concentration so as to investigate the stimuli responsive sorption behaviour. Graft copolymers showed better results than guar gum with percent dye uptake (Du) of 97.588 % in 24 h contact time, 35 °C temperature, 9.4 pH at 150.00 ppm dye feed concentration as compared to Guar gum which only showed 85.260 % dye uptake at alike dye fed concentration. The kinetic behaviour of the polymeric samples was evaluated by applying many adsorption isotherms and kinetic models. The value of 1/n was between 0 â†’ 1 showing that there was physisorption of the BB dye that took place on the surface of the polymers. Thermodynamics of BB Y adsorption onto hydrogels was investigated concerning the Van't Hoff equation. -∆G° values obtained from the curve proved the spontanity of the process. Within the context of adsorption efficiency, an investigation was conducted to examine the process of sorption of Bismarck brown Y dye from aqueous solutions. The graft copolymers demonstrated remarkable adsorption abilities, achieving a dye uptake (Du) of 97.588 % over a 24-h period at a temperature of 35 °C, pH level of 9.4, and a dye concentration of 150.00 ppm. The raised adsorption capacity was additionally corroborated by the application of several adsorption isotherms and kinetic models, which indicated that physisorption is the prevailing process/mechanism. Additionally, the thermodynamic research, utilising the Van't Hoff equation, validated the spontaneity of the adsorption phenomenon, as evidenced by the presence of a negative ∆G° values. The thermodynamic analysis revealed herein establishes a strong scientific foundation for the effectiveness of adsorbent composed of graft copolymers based on guar gum. The research conclude the efficiency of the guar gum based grafted copolymers for the water remediation as efficient adsorbents. The captured dye can be re-utilised and the hydrogels can be used for the same purpose in number of cycles.

Biological investigation of a novel nanocomposite based on xanthan gum-alginate hydrogel/PVA, incorporated with ZnMnFe2O4 nanoparticles.

In light of the need to create new materials that are safe for use in biomedical applications like wound healing and tissue engineering, a unique nanocomposite was formulated and produced in the current investigation. A biocompatible hydrogel was created using natural polymers xanthan gum (XG) and alginate (Alg). In order to enhance the mechanical characteristics of the natural polymer-based hydrogels, polyvinyl alcohol (PVA) was added to the hydrogel matrix. Subsequently, the XG-Alg hydrogel/PVA structure was combined with ZnMnFe2O4 nanoparticles in order to augment the antibacterial efficacy of the biomaterial. The XG-Alg hydrogel/PVA/ZnMnFe2O4 nanocomposite was analyzed using XRD, EDX, FT-IR, TGA, and FE-SEM techniques to determine its properties. In addition, the mechanical properties of the pure hydrogel were compared to those of the XG-Alg hydrogel/PVA/ZnMnFe2O4 nanocomposite. The nanocomposite exhibited a biocompatibility of 96.45 % and 94.32 % with HEK293T cell lines after 24 h and 48 h of incubation, respectively, in biological evaluations. Furthermore, a significant antibacterial efficacy was demonstrated against both gram-positive S. aureus and gram-negative E. coli bacteria. The findings suggest that the developed XG-Alg hydrogel/PVA/ZnMnFe2O4 nanocomposite has promising qualities for use in biomedical fields, such as tissue engineering.

In Silico Quantification of Intersubject Variability on Aerosol Deposition in the Oral Airway.

The extrathoracic oral airway is not only a major mechanical barrier for pharmaceutical aerosols to reach the lung but also a major source of variability in lung deposition. Using computational fluid dynamics, deposition of 1−30 µm particles was predicted in 11 CT-based models of the oral airways of adults. Simulations were performed for mouth breathing during both inspiration and expiration at two steady-state flow rates representative of resting/nebulizer use (18 L/min) and of dry powder inhaler (DPI) use (45 L/min). Consistent with previous in vitro studies, there was a large intersubject variability in oral deposition. For an optimal size distribution of 1−5 µm for pharmaceutical aerosols, our data suggest that >75% of the inhaled aerosol is delivered to the intrathoracic lungs in most subjects when using a nebulizer but only in about half the subjects when using a DPI. There was no significant difference in oral deposition efficiency between inspiration and expiration, unlike subregional deposition, which shows significantly different patterns between the two breathing phases. These results highlight the need for incorporating a morphological variation of the upper airway in predictive models of aerosol deposition for accurate predictions of particle dosimetry in the intrathoracic region of the lung.

Prevalence of pharmaceuticals and personal care products, microplastics and co-infecting microbes in the post-COVID-19 era and its implications on antimicrobial resistance and potential endocrine disruptive effects.

The COVID-19 (coronavirus disease 2019) pandemic's steady condition coupled with predominance of emerging contaminants in the environment and its synergistic implications in recent times has stoked interest in combating medical emergencies in this dynamic environment. In this context, high concentrations of pharmaceutical and personal care products (PPCPs), microplastics (MPs), antimicrobial resistance (AMR), and soaring coinfecting microbes, tied with potential endocrine disruptive (ED) are critical environmental concerns that requires a detailed documentation and analysis. During the pandemic, the identification, enumeration, and assessment of potential hazards of PPCPs and MPs and (used as anti-COVID-19 agents/applications) in aquatic habitats have been attempted globally. Albeit receding threats in the magnitude of COVID-19 infections, both these pollutants have still posed serious consequences to aquatic ecosystems and the very health and hygiene of the population in the vicinity. The surge in the contaminants post-COVID also renders them to be potent vectors to harbor and amplify AMR. Pertinently, the present work attempts to critically review such instances to understand the underlying mechanism, interactions swaying the current health of our environment during this post-COVID-19 era. During this juncture, although prevention of diseases, patient care, and self-hygiene have taken precedence, nevertheless antimicrobial stewardship (AMS) efforts have been overlooked. Unnecessary usage of PPCPs and plastics during the pandemic has resulted in increased emerging contaminants (i.e., active pharmaceutical ingredients and MPs) in various environmental matrices. It was also noticed that among COVID-19 patients, while the bacterial co-infection prevalence was 0.2-51%, the fungi, viral, protozoan and helminth were 0.3-49, 1-22, 2-15, 0.4-15% respectively, rendering them resistant to residual PPCPs. There are inevitable chances of ED effects from PPCPs and MPs applied previously, that could pose far-reaching health concerns. Furthermore, clinical and other experimental evidence for many newer compounds is very scarce and demands further research. Pro-active measures targeting effective waste management, evolved environmental policies aiding strict regulatory measures, and scientific research would be crucial in minimizing the impact and creating better preparedness towards such events among the masses fostering sustainability.

Design, Synthesis and Studies on Novel Polymeric Prodrugs of Erlotinib for Colon Drug Delivery.

AIMS: In the present study, polymer-drug conjugates were synthesized based on azo-bond cleavage drug delivery approach for targeting erlotinib as an anticancer drug specifically to the colon for the proficient treatment of colon cancer. BACKGROUND: Colon Cancer (CC) is the third commonly detected tumor worldwide and makes up about 10% of all cases of cancers. Most of the chemotherapeutic drugs available for treating colon cancer are not only toxic to cancerous cells but also to the normal healthy cells. Among the various approaches to get rid of the adverse effects of anticancer agents, prodrugs are one of the most imperative approaches. OBJECTIVE: The objective of the study is to chemically modify the erlotinib drug through azo-bond linkage and suitable spacer which will be finally linked to the polymeric backbone to give the desired polymer linked prodrug. The azo reductase enzyme present in the colon is supposed to cleave the azo-bond specifically and augment the drug release at the colon. METHODS: The synthesized conjugates were characterized by IR and 1H-NMR spectroscopy. The cleavage of aromatic azo-bond resulted in a potential colon-specific liberation of drug from conjugate studied in rat fecal contents. In vitro release profiles of polyphosphazene-linked conjugates of erlotinib have been studied at pH 1.2, pH 6.8 and pH 7.4. The stability study was designed to exhibit that free drug was released proficiently and unmodified from polyphosphazene-erlotinib conjugates having aromatic azo-bond in artificial colon conditions. RESULTS: The synthesized conjugates were demonstrated to be stable in simulated upper gastrointestinal tract conditions. The drug release kinetics shows that all the polymer-drug conjugates of erlotinib follow zero-order release kinetics which indicates that the drug release from the polymeric backbone is independent of its concentration. Kinetic study of conjugates with slope (n) shows the anomalous type of release with an exponent (n) > 0.89 indicating a super case II type of release. CONCLUSION: These studies indicate that polyphosphazene linked drug conjugates of erlotinib could be promising candidates for the site-specific treatment of colon cancer with the least detrimental side-effects.

Production and characterization of Komagataeibacter xylinus SGP8 nanocellulose and its calcite based composite for removal of Cd ions.

In the present study, fermentative production of bacterial nanocellulose (BNC) by using Komagataeibacter xylinus strain SGP8 and characterization of nanocellulose is presented. The bacterium was able to produce 1.82 g L-1 of cellulose in the form of pellicle in standard Hestrin-Schramn (HS) medium. The morpho-structural characterization of the BNC using scanning electron microscopy (SEM) and X-ray diffraction (XRD) studies, respectively revealed nanofibrillar structure and high crystallinity index (~86%). The thermogravimetric analysis (TGA) showed the stability of BNC up to 280 °C, further rise in temperature to 350 °C results in depolymerization of the sample. In order to show the applicability of produced BNC, it was modified first using calcite (CaCO3) and thereafter characterized using SEM, XRD, FTIR, and TGA studies. The BNC-CaCO3 composites as a sorbent resulted in >99% removal of initial 10 mg L-1 of Cd (II) at pH 5, 7 and 9 after 12 h of treatment. Moreover, the composite was also found to be competent in removing high concentrations of Cd (25 and 50 mg L-1) from the solution (69-70%). Overall, the above results suggest that cellulose produced by K. xylinus strain SGP8 showed excellent material properties, and modified BNC (BNC-CaCO3 composite) could effectively be used for remediation of toxic levels of Cd from the contaminated system.

Industrial wastes: Fly ash, steel slag and phosphogypsum- potential candidates to mitigate greenhouse gas emissions from paddy fields.

Waste management and global warming are the two challenging issues of the present global scenario. Increased human population has set the platform for rapid industrialization and modern agriculture. The industries such as energy, steel, and fertilizers play a significant role in improving the social, and economic status of human beings. The industrial production of energy (that involves combustion of coal), production of steel items and diammonium ammonium fertilizer generate a huge amount of wastes such as fly ash (FA), steel slag (SS) and phosphogypsum (PG), respectively. Inappropriate dumping of any kind of waste poses a threat to the environment, therefore, scientific management of waste is required to reduce associated environmental risks. These wastes i.e. SS, FA, and PG being rich sources of oxides of calcium (CaO), silicon (SiO2), iron (FeO), and aluminum (Al2O3), etc. may affect the release of greenhouse gases from the soil. The information associated with the application of FA, SS, and PG onto the paddy fields and their impacts on methane and nitrous oxide emissions are highly fragmented and scarce. The present review extensively and critically explores the available information with respect to the effective utilization of FA, SS, and PG in paddy cultivation, their potential to mitigate greenhouse gases emission and their associated mechanisms. The fine grid assessment of these waste management provides new insight into the next level research and future policy options for industries and farmers.

Incorporation of Smooth Muscle Cells Derived from Human Adipose Stem Cells on Poly(Lactic-co-Glycolic Acid) Scaffold for the Reconstruction of Subtotally Resected Urinary Bladder in Athymic Rats.

BACKGROUND: The urinary tract can be affected by both congenital abnormalities as well as acquired disorders, such as cancer, trauma, infection, inflammation, and iatrogenic injuries, all of which may lead to organ damage requiring eventual reconstruction. As a gold standard, gastrointestinal segment is used for urinary bladder reconstruction. However, one major problem is that while bladder tissue prevents reabsorption of specific solutes, gastrointestinal tissue actually absorbs them. Therefore, tissue engineering approach had been attempted to provide an alternative tissue graft for urinary bladder reconstruction. METHODS: Human adipose-derived stem cells isolated from fat tissues were differentiated into smooth muscle cells and then seeded onto a triple-layered PLGA sheet to form a bladder construct. Adult athymic rats underwent subtotal urinary bladder resection and were divided into three treatment groups (n = 3): Group 1 ("sham") underwent anastomosis of the remaining basal region, Group 2 underwent reconstruction with the cell-free scaffold, and Group 3 underwent reconstruction with the tissue-engineered bladder construct. Animals were monitored on a daily basis and euthanisation was performed whenever a decline in animal health was detected. RESULTS: All animals in Groups 1, 2 and 3 survived for at least 7 days and were followed up to a maximum of 12 weeks post-operation. It was found that by Day 14, substantial ingrowth of smooth muscle and urothelial cells had occurred in Group 2 and 3. In the long-term follow up of group 3 (tissue-engineered bladder construct group), it was found that the urinary bladder wall was completely regenerated and bladder function was fully restored. Urodynamic and radiological evaluations of the reconstructed bladder showed a return to normal bladder volume and function.Histological analysis revealed the presence of three muscular layers and a urothelium similar to that of a normal bladder. Immunohistochemical staining using human-specific myocyte markers (myosin heavy chain and smoothelin) confirmed the incorporation of the seeded cells in the newly regenerated muscular layers. CONCLUSION: Implantation of PLGA construct seeded with smooth muscle cells derived from human adipose stem cells can lead to regeneration of the muscular layers and urothelial ingrowth, leading to formation of a completely functional urinary bladder.

Nanoparticle-based targeted drug delivery.

Nanotechnology could be defined as the technology that has allowed for the control, manipulation, study, and manufacture of structures and devices in the "nanometer" size range. These nano-sized objects, e.g., "nanoparticles", take on novel properties and functions that differ markedly from those seen from items made of identical materials. The small size, customized surface, improved solubility, and multi-functionality of nanoparticles will continue to open many doors and create new biomedical applications. Indeed, the novel properties of nanoparticles offer the ability to interact with complex cellular functions in new ways. This rapidly growing field requires cross-disciplinary research and provides opportunities to design and develop multifunctional devices that can target, diagnose, and treat devastating diseases such as cancer. This article presents an overview of nanotechnology for the biologist and discusses the attributes of our novel XPclad((c)) nanoparticle formulation that has shown efficacy in treating solid tumors, single dose vaccination, and oral delivery of therapeutic proteins.

Knowledge about tuberculosis among pulmonary tuberculosis patients: A cross-sectional study from Uttarakhand.

BACKGROUND: Tuberculosis (TB) is a major health problem in India. The Revised National TB Control Programme (RNTCP) is working towards elimination of TB in the country by 2025. As the RNTCP relies on passive case finding, it is crucial for the success of the RNTCP that TB patients have knowledge about their disease. The present study aimed to assess the knowledge of TB among pulmonary TB (PTB) patients. MATERIALS AND METHODS: A cross-sectional questionnaire based study using a pretested semi-structured questionnaire among new and previously treated PTB patients at Haldwani Block of Nainital District of Uttarakhand State of North India. Data was analyzed using the software Epi Info version 7.2.0.1. RESULTS: A total of 111 PTB patients with mean age of 36.3 years were included for final analysis. Only 43.2% PTB patients were aware that TB is caused by germs, 48.6% knew that it is not a hereditary disease. Only 13.5% PTB patients knew that vaccine is available and majority (68.5%) were aware of covering mouth and nose while coughing and sneezing for prevention of the disease. Overall, only two-third (65%) patients had good knowledge about TB. CONCLUSIONS: About one-third of PTB patients had poor knowledge about TB. This highlights that to achieve elimination of TB, RNTCP needs to change the present information, education, and communication (IEC) system which is based on a bio-medical framework, and to design a culturally sensitive health education system. Alternatively, the Programme needs to shift from passive case finding to active case finding strategy.

Hyaluronic acid tethered pH-responsive alloy-drug nanoconjugates for multimodal therapy of glioblastoma: An intranasal route approach.

In the present investigation, FePt alloy nanoparticles were synthesized with controlled size and elemental composition followed by surface modification using (3-Aminopropyl) triethoxysilane (APTES). Lenalidomide was covalently bound to FePt-NH2 by pH sensitive hydrazone bonding. Hyaluronic acid was conjugated to amino groups of APTES while lactoferrin (Lf) was directly conjugated to excess carboxylic group present on hyaluronic acid (HA) to form surface modified pH sensitive alloy-drug nanoconjugates (SPANs). The multifunctional nanoconjugates were characterized and evaluated using extensive in vitro and in vivo techniques. The nanoconjugates demonstrated excellent heating ability on exposure to alternating magnetic field and near-infrared laser irradiation. The acidic microenvironment of lysozome triggered release of LND from SPANs. Owing to leaching of Fe and Pt contents, SPANs demonstrated ability to generate reactive oxygen species (ROS) in U87MG cell line which further enhanced therapeutic effect of SPANs. Significant difference in cell viability suppression was observed in in vitro photothermal, chemo-photothermal and chemo-magnetophotothermal killing of cancer cells using SPANs in U87MG cell lines. Significant difference in heating ability and cell cytotoxicity of SPANs in comparison to alternative magnetic field and NIR irradiation was observed for DUAL-mode exposure of SPANs. The results of cellular internalization study showed efficient internalization of SPANs inside U87MG cells. The in vivo results (both qualitative and quantitative) confirmed enhanced uptake of SPANs in brain after intranasal administration with enhanced nasal and mucus penetration owing to presence of Lf. No significant interaction was observed with ECM and mucin due to presence of carboxyl group on SPANs.

Effect of unsaturated bonds in the sn-2 acyl chain of phosphatidylcholine on the membrane-damaging action of Clostridium perfringens alpha-toxin toward liposomes.

Clostridium perfringens alpha-toxin degrades phosphatidylcholine (PC) in the bilayer of liposomes and destroys the membrane. The effect of the type and position of unsaturation in the fatty acyl chain of PC (18:0/18:1 PC) synthesized on the toxin-induced leakage of carboxyfluorescein (CF) from PC liposomes was examined. Differential scanning calorimetry showed that the phase transition temperature (T(m)) was minimal when the triple bond was positioned at C (9) in the sn-2 acyl chain. The toxin-induced CF leakage decreased with the migration of the bond from C (9) to either end of the acyl chain in PC. The PC containing the cis-double bond had a similar T(m) to that with the triple bond, but a lower value than the PC containing the trans-double bond. Furthermore, the toxin-induced leakage from liposomes composed of PC containing the cis-double bond resembled that with PC having the triple bond and was greater than that from liposomes with PC having the trans-double bond. The binding of a H148G mutant to PC liposomes showed a reciprocal relationship in terms of the T(m) value of PC containing the triple bond. These results indicate that the toxin-induced membrane damage is closely related to membrane fluidity in liposomes.

A novel gellan-PVA nanofibrous scaffold for skin tissue regeneration: Fabrication and characterization.

In this investigation, we have introduced novel electrospun gellan based nanofibers as a hydrophilic scaffolding material for skin tissue regeneration. These nanofibers were fabricated using a blend mixture of gellan with polyvinyl alcohol (PVA). PVA reduced the repulsive force of resulting solution and lead to formation of uniform fibers with improved nanostructure. Field emission scanning electron microscopy (FESEM) confirmed the average diameter of nanofibers down to 50 nm. The infrared spectra (IR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis evaluated the crosslinking, thermal stability and highly crystalline nature of gellan-PVA nanofibers, respectively. Furthermore, the cell culture studies using human dermal fibroblast (3T3L1) cells established that these gellan based nanofibrous scaffold could induce improved cell adhesion and enhanced cell growth than conventionally proposed gellan based hydrogels and dry films. Importantly, the nanofibrous scaffold are biodegradable and could be potentially used as a temporary substrate/or biomedical graft to induce skin tissue regeneration.

Design, synthesis and evaluation of antimalarial potential of polyphosphazene linked combination therapy of primaquine and dihydroartemisinin.

Various polymer drug conjugates (13-16) such as primaquine and dihydroartemisinin conjugated 2-propoxy substituted polyphosphazenes (13), primaquine and dihydroartemisinin conjugated 4-acetamidophenoxy substituted polyphosphazenes (14), primaquine and dihydroartemisinin conjugated 4-formyl substituted polyphosphazenes (15) and primaquine and dihydroartemisinin conjugated 4-aminoethylbenzoate substituted polyphosphazenes (16) were synthesized using substituted polyphosphazenes as polymer and primaquine and dihydroartemisinin as combination antimalarial pharmacophores and formulated to nanoparticles to achieve novel controlled combined drug delivery approach for radical cure of malaria. The polymeric backbone was suitably substituted to impart different physicochemical properties. The polymer-drug conjugates were characterized by IR, (1)H NMR, (31)P NMR and their molecular weights were determined by Gel Permeation Chromatography. The thermal properties of the conjugates (13-16) were studied by DSC and TGA. The conjugates (13-16) were then formulated to nanoparticles formulations to increase their uptake by hepatocytes and to achieve targeted drug delivery. The nanoparticle formulations were characterized by Zeta Sizer and their morphology were studied by TEM (Transmission Electron Microscopy) imaging. The nanoparticles formulations exhibited biphasic in vitro drug release profile, the initial burst release followed by a sustained release owing to the non-fickian diffusion during first step release and fickian diffusion during second step release. In vivo antimalarial efficacy was tested using Plasmodium berghei (NK65 resistant strain) infected swiss albino mice at different doses. The combination therapy exhibited promising antimalarial efficacy at lower doses in comparison to the standard drug combination. Further, this combination therapy provided protection over 35days without any recrudescence, thus proving to be effective against resistant malaria. The study provides an alternative combination regimen found to be effective in the treatment of resistant malaria.