Specific Lipid Studies in Complex Membranes by Solid-State NMR Spectroscopy.

Specific interactions with phospholipids are often critical for the function of proteins or drugs, but studying these interactions at high resolution remains difficult, especially in complex membranes that mimic biological conditions. In principle, molecular interactions with phospholipids could be directly probed by solid-state NMR (ssNMR). However, due to the challenge to detect specific lipids in mixed liposomes and limited spectral sensitivity, ssNMR studies of specific lipids in complex membranes are scarce. Here, by using purified biological 13 C,15 N-labeled phospholipids, we show that we can selectively detect traces of specific lipids in complex membranes. In combination with 1 H-detected ssNMR, we show that our approach provides unprecedented high-resolution insights into the mechanisms of drugs that target specific lipids. This broadly applicable approach opens new opportunities for the molecular characterization of specific lipid interactions with proteins or drugs in complex fluid membranes.

Nano-Co-Delivery of Berberine and Anticancer Drug Using PLGA Nanoparticles: Exploration of Better Anticancer Activity and In Vivo Kinetics.

PURPOSE: Combinatorial approach can be beneficial for cancer treatment with better patient recovery. Co-delivery of natural and synthetic anticancer drug not only valuable to achieve better anticancer effectivity but also to ascertain toxicity. This study was aimed to co-deliver berberine (natural origin) and doxorubicin (synthetic origin) utilizing conjugation/encapsulation strategy through poly (lactic-co-glycolic acid) (PLGA) nanoparticles. METHODS: Doxorubicin was efficiently conjugated to PLGA via carbodiimide chemistry and the PLGA-doxorubicin conjugate (PDC) was used for encapsulation of berberine (PDBNP). RESULTS: Significant anti-proliferative against MDA-MB-231 and T47D breast cancer cell lines were observed with IC50 of 1.94 ± 0.22 and 1.02 ± 0.36 µM, which was significantly better than both the bio-actives (p < 0.05). The ROS study revealed that the PDBNP portrayed the slight increase in the reactive oxygen species (ROS) pattern in MDA-MB-231 cell line in a dose-dependent manner, while in T47D cells, no significant change in ROS was seen. PDBNP exhibits significant alteration (depolarization) in mitochondrial membrane permeability and arrest of cell cycle progression at sub G1 phase while the Annexin V/PI assay followed by confocal microscopy resulted into cell death mode to be because of necrosis against MDA-MB-231 cells. In vivo studies in Sprague Dawley rats revealed almost 14-fold increase in half life and a significant increase in plasma drug concentration. CONCLUSION: The overall approach of PLGA based co-delivery of doxorubicin and berberine witnessed synergetic effect and reduced toxicity as evidenced by preliminary toxicity studies.

Enhancing the Solubility of Fenofibrate by Nanocrystal Formation and Encapsulation.

Development of techniques to enhance bioavailability of drugs having poor water solubility is a big challenge for pharmaceutical industry. Solubility can be enhanced by particle size reduction and encapsulation using hydrophilic polymers. Fenofibrate (FF) is a drug for regulating lipids. Multi-fold enhancement in solubility of FF has been achieved by nanocrystal formation in the present study. Nanoparticles were prepared by an evaporation-assisted solvent-antisolvent interaction (EASAI) approach. Water-soluble polymers, viz. polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and hydroxypropyl methylcellulose (HPMC), were used to encapsulate and thus control the particle size of FF nanocrystals. Spherical particles having average particle size well below 30 nm could be prepared under optimum conditions. Almost complete release of the drug molecules from the polymer-stabilized nanocrystals within 2 h was clearly evident from the in vitro drug release studies. Infrared (FTIR) spectroscopy indicated the absence of solvent impurities and any strong interaction between the drug and stabilizers. The polymorphic form of raw-FF was retained in the nanoparticles as per the X-ray diffraction (XRD) patterns. Lower crystallinity of the nanoformulated samples compared to raw-FF was confirmed by differential scanning calorimetric (DSC) studies.

Structural and functional analysis of botulinum neurotoxin subunits for pH-dependent membrane channel formation and translocation.

The structure-function relationship of Botulinum Neurotoxin (BoNT) proteins is greatly influenced by pH. While the low pH of endosome favors membrane interaction of the heavy chain (HC) for the formation of a membrane channel and translocation of the light chain (LC), the catalytic activity of the LC requires a neutral pH for cleavage of the soluble NSF attachment protein receptor (SNARE) complex in the cytosol. In this study, we monitored secondary structural characteristics of LC, HC and holotoxin at individual pHs 4.5 and 7.2 and at the transition pH4.5 to 7.2 to identify the structural signatures underlying their function. The HC showed higher thermal stability at pH4.5 with a melting temperature (Tm) of 60.4°C. The structural analysis of HC in the presence of liposomes showed no difference in ellipticity with that of HC at pH7.2 at 208 and 222 nm but a 25.2% decrease in ellipticity at 208 nm at acidic pH, indicating low pH-induced structural changes that might facilitate interaction with the membrane. Further, HC showed 18% release of K+ ions from liposomes at pH4.5 as against 6% at neutral pH, reinforcing its role in membrane channel formation. LC on the other hand, showed maximum ellipticity at pH7.2, a condition that is relevant to its endopeptidase activity in the cytosol of the neurons. Also, the similarity in the structures at pH7.2 and transition pH4.5 to 7.2 suggested that the flexibility acquired by the protein at low pH was reversible upon exposure to neutral pH for cleavage of SNARE proteins.

Exploring Incision Options for Mandibular Fractures: A Review of Vestibular and Crevicular Approach.

The approach to mandibular fractures remains a contentious topic, with the vestibular and crevicular approaches being prominent incision options, each offering distinct advantages. This review explores the comparative benefits of crevicular incisions over the vestibular approach, focusing on ease of surgical access, better fracture reduction, and enhanced soft tissue healing. Along with a thorough literature review, a case report is also presented to exemplify the successful implementation of crevicular incision in treating a mandibular fracture, emphasizing on its key advantages, which include decreased risk of nerve injury and enhanced patient comfort, underscoring the clinical benefits of this approach. By synthesizing existing literature and case report findings, this review supports the adoption of crevicular incision as a preferred approach for various mandibular fracture cases. This approach offers clinicians a reduced surgical time, good soft tissue adaptation, improved surgical outcomes, and patient well-being.

Harnessing extracellular vesicles-mediated signaling for enhanced bone regeneration: novel insights into scaffold design.

The increasing prevalence of bone replacements and complications associated with bone replacement procedures underscores the need for innovative tissue restoration approaches. Existing synthetic grafts cannot fully replicate bone vascularization and mechanical characteristics. This study introduces a novel strategy utilizing pectin, chitosan, and polyvinyl alcohol to create interpenetrating polymeric network (IPN) scaffolds incorporated with extracellular vesicles (EVs) isolated from human mesenchymal stem cells (hMSCs). We assess the osteointegration and osteoconduction abilities of these modelsin vitrousing hMSCs and MG-63 osteosarcoma cells. Additionally, we confirm exosome properties through Transmission Electron Microscopy (TEM), immunoblotting, and Dynamic Light Scattering (DLS).In vivo, chick allantoic membrane assay investigates vascularization characteristics. The study did not includein vivoanimal experiments. Our results demonstrate that the IPN scaffold is highly porous and interconnected, potentially suitable for bone implants. EVs, approximately 100 nm in size, enhance cell survival, proliferation, alkaline phosphatase activity, and the expression of osteogenic genes. EVs-mediated IPN scaffolds demonstrate promise as precise drug carriers, enabling customized treatments for bone-related conditions and regeneration efforts. Therefore, the EVs-mediated IPN scaffolds demonstrate promise as precise carriers for the transport of drugs, allowing for customized treatments for conditions connected to bone and efforts in regeneration.

In vitro degradation and erosion behavior of commercial PLGAs used for controlled drug delivery.

Copolymers of lactic (or lactide) and glycolic (or glycolide) acids (PLGAs) are among the most commonly used materials in biomedical applications, such as parenteral controlled drug delivery, due to their biocompatibility, predictable degradation rate, and ease of processing. Besides manufacturing variables of drug delivery vehicles, changes in PLGA raw material properties can affect product behavior. Accordingly, an in-depth understanding of polymer-related "critical quality attributes" can improve selection and predictability of PLGA performance. Here, we selected 19 different PLGAs from five manufacturers to form drug-free films, submillimeter implants, and microspheres and evaluated differences in their water uptake, degradation, and erosion during in vitro incubation as a function of L/G ratio, polymerization method, molecular weight, end-capping, and geometry. Uncapped PLGA 50/50 films from different manufacturers with similar molecular weights and higher glycolic unit blockiness and/or block length values showed faster initial degradation rates. Geometrically, larger implants of 75/25, uncapped PLGA showed higher water uptake and faster degradation rates in the first week compared to microspheres of the same polymers, likely due to enhanced effects of acid-catalyzed degradation from PLGA acidic byproducts unable to escape as efficiently from larger geometries. Manufacturer differences such as increased residual monomer appeared to increase water uptake and degradation in uncapped 50/50 PLGA films and poly(lactide) implants. This dataset of different polymer manufacturers could be useful in selecting desired PLGAs for controlled release applications or comparing differences in behavior during product development, and these techniques to further compare differences in less reported properties such as sequence distribution may be useful for future analyses of PLGA performance in drug delivery.

Surgical, Clinical, and Radiological Outcomes Analysis of Craniovertebral Junction Anomalies Cases: An Institutional Experience.

Objective The aim of this study was to evaluate the clinical and radiological outcomes analysis of craniovertebral junction (CVJ) anomalies cases. Materials and Methods Retrospective analysis of 43 CVJ anomalies cases, which were surgically managed at Uttar Pradesh University of Medical Sciences, Saifai, Etawah, Uttar Pradesh, India, from period between June 2015 and June 2019. They were analyzed for age, sex, clinical characteristics, radiological diagnosis, and treatment given. Patient's clinical and radiological status was assessed pre- and postoperatively during time of discharge and at 6 months of follow-up. For clinical assessment we used visual analogue scale (VAS) and Nurick grading system. Radiological assessment was done by atlantodental interval (ADI), craniobasal angle, and craniometric lines. Overall outcomes were depicted as favorable, stabilized, and mortality at 6 to 18 months (mean 12.69 ± 3.77) of follow-up. Results The age range of our cases was 7 to 71 years (mean 29.93 ± 17.39). Male-to-female ratio was 2.91:1. Majority of the cases were presented with neck pain ( n = 38; 88.37%), motor weakness ( n = 35; 81.40%), and sensory deficits ( n = 25; 58.14%). Congenital atlantoaxial dislocation ( n = 31; 72.09) was the most common CVJ anomaly. Clinically, there were significant improvements in VAS ( p = 0.001) and Nurick grade ( p = 0.007) postoperatively. Radiologically, ADI ( p = 0.003) had decreased, clivus canal angle ( p = 0.005) become less acute, and odontoid process ( p = 0.003 for McRae's line) goes downwards in postoperative period. Bony fusion was achieved in 41 (95.35%) cases. Out of 43, 73% cases had favorable outcomes, 21% were stabilized, and mortality was seen in 2.33% cases at 6 months (mean ± standard deviation = 12.69 ± 3.77) of follow-up. Conclusion Proper preoperative evaluation and selection of individualized surgical technique was the key for excellent clinical and radiological outcomes with minimal complications.

Antioxidative and radioprotective activities of semiquinone glucoside derivative (SQGD) isolated from Bacillus sp. INM-1.

A semiquinone glucoside derivative (SQGD) was isolated from a radioresistant bacterium Bacillus sp. INM-1 and its antioxidant and radioprotective activities were evaluated using in vitro assays. Natural stable free radical properties of SQGD in solid as well as in solution form were estimated using Electron Paramagnetic Resonance (EPR) spectrometry. Results of the study were demonstrated high reducing power (1.267 ± 0.03356 U(abs)) and nitric oxide radicals scavenging activity (34.684 ± 2.132%) of SQGD. Maximum lipid peroxidation inhibitory activity of SQGD was found to be 74.09 ± 0.08% at 500 µg/ml concentration. Similarly, significant (39.54%; P < 0.05) protection to the liposomal artificial membrane against gamma radiation was observed by SQGD in terms of neutralization of gamma radiation-induced TBARS radicals in vitro. OH(-) radicals scavenging efficacy of SQGD was estimated in terms of % inhibition in deoxy D: -ribose degradation by non-site-specific and site-specific assay. The maximum (54.01 ± 1.01%) inhibition of deoxy D: -ribose degradation was observed in non-site-specific manner, whereas, site-specific inhibition was observed to be 46.36 ± 0.5% at the same concentration (250 µg/ml) of SQGD. EPR spectroscopic analysis of the SQGD indicated ~80% reduction of DPPH radicals at 6.4% concentration. EPR spectral analysis of SQGD was revealed an appearance of very strong EPR signal of 2.00485 (crystalline form) and 2.00520 (solution form) g(y) tensor value, which were an established characteristic of o-semiquinone radicals. Therefore, it can be concluded that SQGD is a natural stable o-semiquinone-type radical, possessing strong antioxidant activities and can effectively neutralize radiation induced free radicals in biological system.

Lignin: Drug/Gene Delivery and Tissue Engineering Applications.

Lignin is an abundant renewable natural biopolymer. Moreover, a significant development in lignin pretreatment and processing technologies has opened a new window to explore lignin and lignin-based bionanomaterials. In the last decade, lignin has been widely explored in different applications such as drug and gene delivery, tissue engineering, food science, water purification, biofuels, environmental, pharmaceuticals, nutraceutical, catalysis, and other interesting low-value-added energy applications. The complex nature and antioxidant, antimicrobial, and biocompatibility of lignin attracted its use in various biomedical applications because of ease of functionalization, availability of diverse functional sites, tunable physicochemical and mechanical properties. In addition to it, its diverse properties such as reactivity towards oxygen radical, metal chelation, renewable nature, biodegradability, favorable interaction with cells, nature to mimic the extracellular environment, and ease of nanoparticles preparation make it a very interesting material for biomedical use. Tremendous progress has been made in drug delivery and tissue engineering in recent years. However, still, it remains challenging to identify an ideal and compatible nanomaterial for biomedical applications. In this review, recent progress of lignin towards biomedical applications especially in drug delivery and in tissue engineering along with challenges, future possibilities have been comprehensively reviewed.

Sonochemical synthesis of carbon dots, mechanism, effect of parameters, and catalytic, energy, biomedical and tissue engineering applications.

Carbon-based nanomaterials are gaining more and more interest because of their wide range of applications. Carbon dots (CDs) have shown exclusive interest due to unique and novel physicochemical, optical, electrical, and biological properties. Since their discovery, CDs became a promising material for wide range of research applications from energy to biomedical and tissue engineering applications. At same time several new methods have been developed for the synthesis of CDs. Compared to many of these methods, the sonochemical preparation is a green method with advantages such as facile, mild experimental conditions, green energy sources, and feasibility to formulate CDs and doped CDs with controlled physicochemical properties and lower toxicity. In the last five years, the sonochemically synthesized CDs were extensively studied in a wide range of applications. In this review, we discussed the sonochemical assisted synthesis of CDs, doped CDs and their nanocomposites. In addition to the synthetic route, we will discuss the effect of various experimental parameters on the physicochemical properties of CDs; and their applications in different research areas such as bioimaging, drug delivery, catalysis, antibacterial, polymerization, neural tissue engineering, dye absorption, ointments, electronic devices, lithium ion batteries, and supercapacitors. This review concludes with further research directions to be explored for the applications of sonochemical synthesized CDs.

Systematic approach of chromone skeleton for detecting Mg2+, ion: Applications for sustainable cytotoxicity and cell imaging possibilities.

The systematic studies of chromone appended novel chemosensors, favored to Mg2+ ion detection, these were analyzed and characterized by different spectroscopic techniques such as NMR, mass spectroscopy, FTIR and optical techniques. The binding demeanor of the ligands was executed with the library of metal ions and shown the good coordination with Mg2+ ion to the ligand's cavity. Both ligands demonstrated good binding behavior with Mg2+ ion. The ligands represented 1: 1 stoichiometry with Mg2+ ions through Job's plot. The low limit of detection of Mg2+ ion was determined as 2.56 × 10-6 and 1.28 × 10-6 for La and Lb respectively. No interference was occurred in Inference study by foreign metal ions that supported the specific detection of Mg2+ ion among the other metal ions. Further, the cytotoxicity assay test of these chromone appended ligands revealed that both ligands and their respective compound with Mg2+ ion shown negligible toxicity with HeLa cancer cell line. Further, due to the fluorescence properties of the ligands, with or without Mg2+ ion was successfully tested in bioimaging experiment of HeLa cancer cell lines and found that ligands with Mg2+ ions represented good imaging with HeLa cancer cell.

Spectroscopic and chemometric evaluation of cling films used for wrapping of foodstuff and illicit drugs.

Thin films of various polymers are currently used for wrapping various food products and illicit drugs worldwide. In thin films, polyvinyl chloride is the third most widely used polymer after the polyethylene and polypropylene. These films usually contain harmful plasticizers such as adipates, phthalates, and citrates along with other additives. Plasticizers adversely affect the human health and therefore, their migration in foodstuff must be monitored carefully. By considering all these facts, this study summarizes the utilities of non-destructive ATR-FTIR spectroscopy in the identification of base polymer as well as plasticizers in various cling films and application of multivariate analysis in the identification and classification of the cling films to their respective groups. In the present research, a considerable transfer of plasticizers from the wrapping material is observed. A spectral library is developed for all 22 cling film samples for further comparison of the unknown sample. The obtained results are promising, especially for classification purposes. The multivariate method significantly provides 100% of cross-validation classification along with 99.13% discrimination. In this study, we have developed a method to compare or link a cling film which somebody uses and found that there is a transfer of plasticizers and other additives into the food and if the manufacturing company disown that this specific cling film does not belong to our company. In such type of cases, this method could link the suspected cling film to their manufacturers with precision and accurateness. The chronic effect of plasticizers on human health can also be linked to the type of cling film the accused was using consistently.

Fluorescent metal-doped carbon dots for neuronal manipulations.

There is a growing need for biocompatible nanocomposites that may efficiently interact with biological tissues through multiple modalities. Carbon dots (CDs) could serve as biocompatible fluorescence nanomaterials for targeted tissue/cell imaging. Important goals toward this end are to enhance the fluorescence quantum yields of the CDs and to increase their targetability to cells. Here, sonochemistry was used to develop a one-pot synthesis of CDs, including metal-doped CDs (M@CDs), demonstrating how various experimental parameters, such as sonication time, temperature, and power of sonication affect the size of the CDs (2-10 nm) and their fluorescence properties. The highest measured quantum yield of emission was ∼16%. Similarly, we synthesized CDs doped with different metals (M@CDs) including Ga, Sn, Zn, Ag, and Au. The interaction of M@CDs with neuron-like cells was examined and showed efficient uptake and low cytotoxicity. Moreover, the influence of the M@CDs on the improvement of neurites during initiation and elongation growth phases were compared with pristine CDs. Our research demonstrates the use of M@CDs for imaging and for neuronal interactions. The M@CD nanocomposites are promising due to their biocompatibility, photo-stability and potential selective affinity, paving the way for multifunctional biomedical applications.

Formulation and physiochemical study of α-tocopherol based oil in water nanoemulsion stabilized with non toxic, biodegradable surfactant: Sodium stearoyl lactate.

The unique properties such as high optical clarity, stability and enhanced bioavailability of nanoemulsion make them useful for food, cosmetic and pharmaceutical industries. In this work, sodium stearoyl lactate and Tween 80 surfactants were collectively used to fabricate alpha tocopherol based oil in water nanoemulsion using high energy ultrasonication method. The spherical nature of pure and drug loaded nanoemulsion has been confirmed with transmission electron microscopy (TEM). The influence of pH, dilution, surfactant concentration and ionic strength on average particle size of pure and nutraceutical (benzylisothiocyanate and curcumin) encapsulated emulsion was examined. The prepared emulsion exhibited good stability up to 90days in salt solution (50-200mM) and different pH conditions. The cumulative release % of benzylisothiocyanate and curcumin was found to be 50.29% in 36h and 89.15% in 150h respectively. The antioxidant activity of pure, benzylisothiocyanate, curcumin and cocktail (benzylisothiocyanate and curcumin) nanoemulsion was calculated with 2,2-diphenyl-1-picrylhydrazyl radical. The IC50 value of different antioxidant showed that benzylisothiocyanate nanoemulsion acted as better antioxidant as compared to pure and curcumin encapsulated nanoemulsion. Also the cell viability of pure nanoemulsion was found to be 24% on hep G2 cell. The effect of UV light irradiation on curcumin and benzylisothiocyanate stability was carried out in different solvent conditions (water/ethanol and nanoemulsion). The degradation of curcumin by the impact of UV light was successfully controlled by trapping in NEm.

PLGA-CTAB curcumin nanoparticles: Fabrication, characterization and molecular basis of anticancer activity in triple negative breast cancer cell lines (MDA-MB-231 cells).

Triple-negative breast cancers (TNBC) are aggressive cancers, which do not control by hormonal therapy or therapies that target HER-2 receptors. Curcumin (Cur) has shown cytotoxic effects in multiple cancer cell lines. However, its medical uses remain limited due to low aqueous solubility and poor bioavailability. Therefore, present study was aimed to fabricate the small positive charge curcumin nanoparticles (CN) by nanoprecipitation methods using PLGA and CTAB, and to evaluate its anticancer efficacy and underlying the mechanism in triple negative breast cancer cell lines (MDA-MB-231 cells). In in-vitro drug release assay, Cur was released from CN by flicking diffusion and anomalous transport process. CN showed a higher cellular incorporation than free Cur resulted in higher cytotoxicity. Checking the anticancer activity at the molecular level, Cur has shown to induce the reactive oxygen species production that subsequently causes the DNA damage and resulting in p38-MAPK activation. The p38-MAPK induce the expression of p16/INKK4a, p21/waf1/cip1 and p53 resulting in a reduction in the level of CDK2, CDK4, cyclin D1 and cyclin E and subsequently cell cycle arrest at G1/S and G2/M phase. It also reduces the expression of DNA repair gene, i.e. BRCA1, BRCA2, Rad51, Rad50, Mre11 and NBS1 resulting in apoptosis induction due to persistent DNA damage. This study presents an effective delivery of curcumin in TNBC cancer cells and it could open the new frontiers in clinical cancer chemotherapy.

Factors Leading to Oro-Facial Herpetic Eruptions in Patients Undergoing Surgery for Vestibular Schwannoma.

OBJECTIVE: To study factors influencing oro-facial herpetic eruptions (HEs) in patients undergoing retromastoid suboccipital craniectomy for vestibular schwannomas (VS). METHODS: A retrospective analysis of the prospectively collected database (from July 2014 to December 2015). A total of 87 patients underwent retromastoid suboccipital craniectomy for VS at our center. For the purpose of analysis the patient subset was divided into 2 groups, HE and non-HE. Pearson χ2 test or Fisher exact test were used to identify the factors. RESULTS: The overall incidence of postoperative HE was less than 1% (0.89%, 26 patients of 2916 cases); whereas after VS surgery, it was 20.69% (18 of 87). Demographic profiles of patients in the 2 groups were comparable. Average tumor size (with HE 3.19 ± 2 × 0.67 cm, non-HE 3.38 ± 2 × 1.07 cm), consistency, and laterality also were comparable between the 2 groups. Factors favoring development of postoperative HEs were large size (12 vs. 22, P = 0.013) and preoperative trigeminal nerve (CN V) involvement (9 of 18, 50%, P = 0.046). All patients developed HE in maxillary division of trigeminal nerve (V2), whereas involvement of ophthalmic (V1) and mandibular (V3) divisions were involved less commonly in combination with V2 (V2, 72.2%; V2 + V3, 22.2%; V1 + V2 + V3, 5.6%). The majority of the patients (55.56%) developed HE on postoperative day 3 and none beyond postoperative day 5. All patients responded to empirical oral acyclovir. CONCLUSIONS: The study highlights the relatively high incidence and factors associated with this rare but benign complication.

Calvarial tuberculosis of the parietal bone: A rare complication after dental extraction.

Tuberculosis (TB) is a well-known endemic in developing countries. However calvarial TB is quiet rare even in such endemic areas. The most common sites affected are the frontal and parietal bones with destruction of both the inner and outer table. We hereby report a young male presenting to us with scalp swelling in the right temporal region with pus discharging sinus after an episode of tooth extraction for dental infection. Radiology revealed a loculated swelling within the right temporalis muscle and an associated bony defect in the right parietal bone. The patient was operated upon and the biopsy was suggestive of tubercular pathology. The patient improved on antitubercular therapy. The rare presentation of calvarial TB occurring secondary to dental infection along with relevant literature is discussed here.

Semiquinone glucoside derivative (SQGD) isolated from Bacillus sp. INM-1 protects against gamma radiation-induced oxidative stress.

In the present study, radioprotective potential of Semiquinone glucoside derivative (SQGD) isolated from radioresistant bacterium Bacillus sp. INM-1 was evaluated. γ-Radiation induced protein carbonylation, plasmid DNA damage, enzyme functional impairment, lipid peroxidation, HO radicals generation and their protection by SQGD was assessed. As a result of SQGD treatment, significant inhibition (p<0.05) in protein carbonylation was observed with BSA. SQGD treatment was found to restore supercoiled (~70±3.21%) form of irradiated plasmid DNA against γ-irradiation. SQGD protects enzymes (EcoR1 and BamH1) against radiation-induced dysfunctioning. SQGD significantly inhibited (p<0.05) lipid peroxidation in liposomes, brain and liver homogenate. Higher HO(•) radicals-averting activity of SQGD was observed in the serum and liver homogenate of C57BL/6 mice against H2O2-induced oxidative stress. In conclusion, SQGD demonstrates excellent radical-scavenging activity towards bio-macromolecules in irradiated environment and can be developed as an ideal radioprotector against radiation-induced oxidative stress in future.

Intracellular delivery of redox cycler-doxorubicin to the mitochondria of cancer cell by folate receptor targeted mitocancerotropic liposomes.

Cancer cells reflect higher level of ROS in comparison to the normal cell, so they become more vulnerable to further oxidative stress induced by exogenous ROS-generating agents. Through this a novel therapeutic strategy has evolved, which involves the delivery of redox cycler-doxorubicin (DOX) to the mitochondria of cancer cell where it acts as a source of exogenous ROS production. The purpose of this study is to develop a liposomal preparation which exhibits a propensity to selectively target cancer cell along with the potential of delivering drug to mitochondria of cell. We have rendered liposomes mitocancerotropic (FA-MTLs) by their surface modification with dual ligands, folic acid (FA) for cancer cell targeting and triphenylphosphonium (TPP) cations for mitochondria targeting. The cytotoxicity, ROS production and cell uptake of doxorubicin loaded liposomes were evaluated in FR (+) KB cells and found to be increased considerably with FA-MTLs in comparison to folic acid appended, mitochondria targeted and non-targeted liposomes. As confirmed by confocal microscopy, the STPP appended liposomes delivered DOX to mitochondria of cancer cell and also showed higher ROS production and cytotoxicity in comparison to folic acid appended and non-targeted liposomes. Most importantly, mitocancerotropic liposomes showed superior activity over mitochondria targeted liposomes which confirm the synergistic effect imparted by the presence of dual ligands - folic acid and TPP on the enhancement of cellular and mitochondrial delivery of doxorubicin in KB cells.