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Hyaluronic acid (HA) coated irinotecan loaded lignin nanoparticles (HDLNPs) were synthesized using ionic interaction method. Optimized nanoparticles were characterized for their active chemotherapeutic targeting potential to CD44 receptors overly-expressed on cancer cells. Blood component interaction studies supported hemocompatible nature of HDLNPs and also demonstrated their sustained plasma residence property. Cell anti-proliferation and mitochondrial depolarization studies on HT-29 cells suggest significantly (p < 0.01) improved chemotherapeutic efficacy of HDLNPs. In vitro cell based studies showed that nanoparticles have retained antioxidant activity of lignin that can prevent cancer relapse. In vivo biodistribution studies in tumor-bearing Balb/c mice confirmed improved drug localization in tumor site for longer duration. Tumor regression and histopathological studies indicated the efficacy ofligand-assisted targeting chemotherapy over the conventional therapy. Hematological and biochemical estimation suggested that irinotecan-associated myelosuppression, liver steatosis and rare kidney failure can be avoided by its encapsulation in HA-coated lignin nanoparticles. HDLNPs were found to be stable over a period of 12 months., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Treatment of skin cancer demands targeted delivery without minimal systemic circulation for maximum therapeutic window. Dermal delivery with nano-formulation offers such advantages. Therefore, present study aims to formulate Lyotropic liquid crystalline nanoparticles (LLC NPs) loaded with Apigenin (API) for dermal delivery using quality by design (QbD) approach for effective permeation resulting in improved bioavailability. Apigenin loaded LLC NPs (API-LLC NPs) were formulated and optimized by applying risk assessment and design of experiments (Box-Behnken Design). The optimized API-LLC NPs showed particle size, PdI and entrapment efficiency of 287.7 ± 9.53 nm, 0.152 ± 0.051 and 80 ± 2.2 % respectively. The optimized API-LLC NPs were characterized for morphology and crystallinity using optical microscopy, TEM, DSC and PXRD. In vitro and ex vivo studies showed sustained release and better permeation profile. CLSM study presented better penetration of API-LLC NPs which were quantitatively confirmed with dermatokinetics. Cytotoxic efficacy assessed on B16F10 cell lines showed a dose-dependent efficacy of API-LLC NPs with an IC 50 of 45.74 ± 0.05. In a nutshell, the developed API-LLC NPs exhibit excellent potential for targeting deeper skin layers thereby can be considered a promising topical drug delivery nanocarrier in the treatment and management of skin cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Lignin nanoparticles synthesis is among recent developments in lignin valorization especially for biomedical applications. In this study, a new technique where complete self-assembling of lignin was ensured by simultaneous solvent displacement and flash pH change was used to optimize particle size of blank lignin nanoparticles (BLNPs) for suitability in cell uptake along with maximized yield. To establish BLNPs as drug carrier, safety studies including hemocompatibility, cytotoxicity and elaborate genotoxicity studies on Drosophila melanogaster as a model organism were done. Finally, irinotecan loaded lignin nanoparticles (DLNPs) were synthesized to establish their drug carrying potential and thorough in vitro characterization was performed. BLNPs with controllable size (⁓152 nm), low polydispersity (<0.2), maximized yield (>65%), negative surface charge (-22 to -23 mV), spherical shape and smooth surface were obtained with acceptable %hemolysis (<2%). In vitro cytotoxicity studies revealed that BLNPs were significantly toxic (74.38 ± 4.74%) in human breast adenocarcinoma (MCF-7), slightly toxic (38.8 ± 4.70%) in human alveolar epithelial adenocarcinoma (A-549) and insignificantly toxic (15.89 ± 2.84%) to human embryonic kidney (HEK-293) cells. BLNPs showed concentration dependent early neuronal defects in Drosophila, but nuclei fragmentation and gut cell damage were absent. Sustained release DLNPs with high drug loading reduced the IC 50 value of irinotecan by almost 3 folds., Competing Interests: Declaration of competing interest The authors associated with this manuscript have observed no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Colon cancer is one of the fatal forms of cancer all round the world with a equal frequency of occurrence in both male and female population. Mutational changes and defects in APC (Adenomatous Polyposis Coli) and DNA mismatch repair genes accompanied by genetic chaos in oncogenic pathways leads to colon cancer. Intensive study on pathogenesis of colon cancer has been made to decipher the mechanisms underlying the development and progress of the disease so as to develop effective treatment. However, a complete therapeutic regimen is still not available for combating this deadly disease. Hurdles faced by chemotherapy include drug resistance due to P-glycoprotein transporters, untoward effects on normal cells, high cost, bio-burden of the therapy, and the most dreadful drawback is cancer relapse. The concept of cancer relapse is related to development of oxidative stress that causes cell apoptosis. If the level of oxidative stress is inadequate to cause apoptosis then it leads to cell dormancy which may revive post chemotherapy. This hypothesis aims to put forward a combinatorial approach that includes utilizing a cost effective, biocompatible and environmentally benign nanoparticulate carrier made up of lignin, loaded with anti-cancer agent and P-gp modulator, and functionalized with ligand for CD44 receptors that are over expressed on cancer cells. Antioxidant effect of lignin will overcome dormancy of cancer cells making it possible for cell cycle specific drugs to kill them and prevent relapse and active targeting will prevent untoward effects on normal cells. Thus a robust and wholesome formulation can be developed to combat colon cancer., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Amikacin (A), a water soluble aminoglycoside antibiotic is commercially available for intravenous administration only. Present investigation is aimed at the development of poly-lactic-co-glycolic acid (PLGA) nanoparticles (A-NPs). 1 for oral permeability enhancement of amikacin. The pharmaceutical attributes of the A-NPs revealed particle size, 260.3 ± 2.05 nm, zeta potential, -12.9 ± 1.12 mV and drug content, 40.10 ± 1.87 μg/mg with spherical shape and smooth surface. In vitro antibacterial studies showed that the A-NPs were active against P. aeruginosa, K. pneumoniae and E. coli. The permeation study across rat ileum showed 2.6-fold improvement in P app for A-NPs than A-S 2 This increase in permeability is due to the uptake of nanoparticles by Peyer's patches of intestinal epithelium and endocytic uptake via enterocytes. Flow cytometric analysis demonstrated 2.2-fold higher uptake of Rh B-NPs 3 than Rh B-S 4 and elucidated the dominance of enterocytes mediated endocytosis of nanoparticles. Furthermore, stability data collected as per ICH guidelines for three months under accelerated conditions had shown that the A-NPs were stable. The purported drug delivery system hence, seems a promising tool to replace successfully the current intravenous therapy and is used to support relevant patient compliance thereby, adding value to the "patient care at home"., (Copyright © 2018. Published by Elsevier B.V.)

Melanoma is one of the most aggressive cancers which has very low response rate and survival rate. Melanoma cells are known to be inherently resistant to the chemotherapy which results in poor outcomes and even failure of the therapy. For this reason, a better understanding of underlying mechanism of melanoma pathogenesis and resistance is required, so that more efficient and novel therapeutic strategies can be developed. Survivin is a protein which is overexpressed in melanoma cells and is known to impart resistance to them against apoptosis. Also, melanoma cells overexpress Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (bFGF) angiogenic growth factors which lead to aggressive angiogenesis in melanoma cells thereby making the treatment more challenging. This hypothesis presents a combinatorial approach against melanoma where an anti-survivin agent and an anti-angiogenic agent are combined with a chemotherapeutic drug and loaded in surface functionalized liposomes in order to target specific mechanisms of melanoma, thus overcoming its resistance. Thus, the study aims to overcome the resistance of melanoma cells by developing a wise combination of drugs and achieve a higher response rate in resistant melanoma model, which is usually not achieved with the existing treatment modalities., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The study focuses on widening up the therapeutic perspective of anti-cancer therapy by entrapping a hydrophilic anticancer drug, topotecan hydrochloride (TOPO) in biodegradable poly (lactide-co-glycolide) (PLGA) matrix to form topotecan nanoparticles (TOPO NPs) by a double emulsion solvent evaporation technique. Statistical optimization using Box-Behnken design showed that sonication time of primary emulsion for 120 s, drug: polymer ratio of 1:12.65, organic phase: external aqueous phase ratio of 1:2.82 and 0.5% w/v of polyvinyl alcohol in the drug containing phase produced TOPO NPs with a size of 243.2 ± 4 nm and an entrapment efficiency of 60.9 ± 2.2%. TOPO NPs illustrated sustained release of TOPO for a week in phosphate buffer saline (PBS) at simulating physiological (pH 7.4) and acidic tumor microenvironmental (pH 6.5) conditions. A dramatic increase in cellular uptake with a corresponding enhanced cytotoxic potency was also displayed by TOPO NPs against human ovarian cancer cells (SKOV3) over time as compared to native drug, TOPO. These findings were further supported by the enhancement of bioavailability (13.05 fold) conferred by TOPO NPs from the in vivo pharmacokinetic study. The study represents a logistic approach for formulating TOPO NPs which can be used as an effective drug delivery system for the treatment of ovarian cancer., (Copyright © 2018. Published by Elsevier B.V.)

Background: Bendamustine HCl, an antineoplastic drug, has a very short life of about 40 minutes which necessitates administration of large doses which leads to increased side effects as well as costs., Objective: The present work describes the fabrication, optimization, and evaluation of bioactive hydroxyapatite nanoparticles to achieve sustained delivery of bendamustine HCl., Methods: Hydroxyapatite nanoparticles (NPs) were prepared by the wet chemical precipitation method by reacting a calcium and phosphate precursor and the reaction was optimized via Box-Behnken DOE. The drug was loaded on particles by physical adsorption. Various analytical studies were performed on the fabricated nanoparticles in addition to biodistribution studies to establish the physicochemical and biological characteristics of the designed formulation., Results: pH of the reactant solution was found to have a more profound effect on the particle size and size distribution in comparison to reactant concentration. The particles were found to have a spherical morphology by SEM. Size of the blank and drug-loaded nanoparticles was found to be 130±20 nm by TEM. Energy Dispersive X-ray Spectroscopy (EDS) studies confirmed the presence of hydroxyapatite as the dominant phase while DSC studies indicated the presence of the drug in its amorphous form after its adsorption on NPs. Tissue distribution studies further suggested that the majority of drug concentration was released in blood rather than the other organs implying low organ toxicity., Conclusion: Bendamustine loaded hydroxyapatite nanoparticles were successfully optimized and fabricated. Favorable results were obtained in in vitro, in vivo, and analytical studies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Nanotechnology-based drug delivery approach has emerged as a promising field, where different kinds of formulations are developed for therapeutic applications. Inflowing of nanomedicine developed through various biomaterials appears to be a game changer in the domain of pharmaceutical and biotechnological industries. Nanomedicines propose to overcome the major constraints of conventional medicine of low solubility and stability, non-adequate pharmacokinetic profiles and side effects., Objectives: Mesoporous Silica Nanoparticles (MSNs) have garnered significant attention in biomedical applications for its multifunctionality. The porous structure of MSNs provides the opportunity for heavy drug loading, controlled release and ligand functionality. From last decades, a lot of interest has been generated owing to the better drug delivery attributes of MSNs to introduce unique biological effects for its suitable therapeutic application., Methods: The review article gives an insight into the current advancement of usage of MSNs in drug delivery for cancer, non-cancer and biosensors based biomedical applications along with technology that is protected by patents., Conclusion: The future success of MSNs is widened because of their valuable characteristic that easily combines with various functionalities which would display enormous potential translational possibilities., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: Rutin, a potent antioxidant, has been reported to reduce the risk of ischemic disease. Our study aims to prepare rutin-encapsulated-chitosan nanoparticles (RUT-CS-NPs) via ionic gelation method and determine its results, based on different parameters i.e. surface morphology characterization, in-vitro or ex-vivo release, dynamic light scattering and differential scanning calorimetry (DSC), for treating cerebral ischemia., Methods: UPLC-ESI-Q-TOF-MS/MS was used to evaluate the optimized RT-CS-NPs1 for brain-drug uptake as well as to follow-up the pharmacokinetics, bio-distrbution, brain-targeting efficiency and potential after intranasal administration (i.n.)., Key Findings: A particle size of <100nm for the formulation, significantly affected by drug:CS ratio, and entrapment efficiency and loading capacity of 84.98%±4.18% and 39.48%±3.16%, respectively were observed for RUT. Pharmacokinetics, bio-distribution, brain-targeting efficiency (1443.48±39.39%) and brain drug-targeting potential (93.00±5.69%) showed enhanced bioavailability for RUT in brain as compared to intravenous administration. In addition; improved neurobehavioral activity, histopathology and reduced infarction volume effects were observed in middle cerebral artery occlusion (MCAO) induced cerebral ischemic rats model after i.n. administration of RUT-CS-NPs., Conclusion: A significant role of mucoadhesive-RT-CS-NPs1 as observed after high targeting potential and efficiency of the formulation prove; RUT-CS-NPs are more effectively accessed and target easily the brain., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Topotecan (TPT) is indicated against a variety of solid tumors, but has restricted clinical use owing to associated pharmaceutical caveats. This study is focused at formulating a successful TPT PLGA nanosystem which ameliorates the rapid conversion of active lactone form of drug to its inactive carboxylate form and consequently improvises its efficacy. TPT PLGA nanoparticles were formulated by a double emulsion-solvent evaporation technique with sequential optimization to obtain desired particle size, PDI, zeta potential, and entrapment efficiency. Stability of TPT was ensured by maintaining an acidic pH in the drug-containing phase and the system was evaluated for in vitro-in vivo performance including cytotoxic potency. The optimized nanosystem had a particle size of 187.33 ± 7.50 nm, a PDI of 0.179 ± 0.05, and an entrapment efficiency of 56 ± 1.2%. Low pH in the interior of nanoparticles stabilized the drug to remain in its active lactone form and revealed a biphasic release pattern till 15 d. Additionally, an in vitro cytotoxicity testing as well as in vivo antitumor efficacy demonstrated a significant potential of higher proliferation inhibition as compared with neat drug (TPT). Thus, the investigation summarized an innovative simple tool for developing stable TPT NPs for effective delivery for treating solid tumors.

The present work evaluates the synergistic anticancer efficacy of bioactive Hydroxyapatite (HA) nanoparticles (HA NPs) loaded with Bendamustine HCl. Hydroxyapatite is a material with an excellent biological compatibility, a well-known fact which was also supported by the results of the Hemolytic studies and a high IC50 value observed in the MTT assay. HA NPs were prepared by the chemical precipitation method and loaded with the drug via physical adsorption. In-vitro release study was performed, which confirmed the sustained release of the drug from the drug loaded HA NPs. MTT assay, Cell Uptake and FACS studies on JURKAT E6.1 cell line and in-vivo pharmacokinetic studies in Wistar rats revealed that the drug loaded HA NPs could be easily internalized by the cells and release drug in a sustained manner. The drug loaded HA NPs showed cytotoxicity similar to the drug solution at 1/10th of the drug content, which indicates a possible synergism between the activity of the anticancer drug and calcium ions derived from the carrier. An increase in intracellular Ca(2+) ions is reported to induce apoptosis in cells. Tumor regression study in Balb/c mice Ehrlich's ascites model presented a similar synergistic efficacy. The drug solution was able to decrease the tumor volume by half, while the drug loaded HA NPs reduced the tumor size by 6 times., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The current investigation aims to present a novel solid lipid-based nanoparticulate system of resveratrol (RV) for the effective treatment of liver cirrhosis. A simplified solvent injection method was employed and the Box-Behnken experimental design was applied for optimization to get a window particle size of 150-200 nm having maximum entrapment efficiency as well as % release. Optimized resveratrol solid lipid nanoparticles (RV-SLNs) (SR-1) of appropriate characteristics (particle size = 191.1 ± 10.44 nm; zeta potential= -13.56 ± 4.14 mV; entrapment efficiency = 75.23 ± 3.85%; maximum % release = 80.53 ± 3.99%) were produced. Differential scanning calorimetry and X-ray diffraction studies were carried out which collectively proved the reduced crystallinity and stability enhancing the effect of the SLNs. Improved drug stability was further established by the appreciable shelf-life of the formulation from International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)-recommended accelerated stability studies. In vivo studies revealed nearly five-fold increase in the bioavailability of SR-1 (AUC0→∞=3411 ± 170.34 µg/ml/h) as compared to RV suspension (AUC0→∞=653.5 ± 30.10 µg/ml/h). Pharmacodynamic data exhibited a significant decrease in the serum biomarker enzymes (serum glutamic oxalo-acetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT) and alkaline phosphatase) after oral administration of RV-SLNs as compared to control and marketed (SILYBON(®)) formulations against paracetamol-induced liver cirrhosis. The effect of the treatment was confirmed by the histopathology of the liver microtome sections. Finally, reverse transcriptase-polymerase chain reaction studies were conducted on isolated liver mRNA from SR-1 treated animals and significant down-regulation of tissue inhibitor of metalloproteinases-1 and nuclear factor-kB was witnessed.

A receptor level interaction of etoposide with P-glycoprotein (P-gp) and subsequent intestinal efflux has an adverse effect on its oral absorption. The present work is aimed to enhance the bioavailability of etoposide by co-administering it with quercetin (a P-gp inhibitor) in dual-loaded polymeric nanoparticle formulation. Poly-lactic-co-glycolic acid (PLGA) nanoparticles were optimized for various parameters like o/w phase volume ratio, poly-vinyl alcohol concentration, PLGA concentration and sonication time. The cytotoxicity studies (MTT assay) revealed a 9- and 11-fold decrease in the IC 50 values for etoposide-loaded nanoparticles (ENP) and etoposide + quercetin dual-loaded nanoparticles (EQNP) when compared to that of free etoposide, respectively, and the results were further supported by florescent-activated cell sorter studies. The confocal imaging of the intestinal sections treated with ENP and EQNP containing fluorescent probe (rhodamine) showed the superiority of the EQNP to permeate deeper. Furthermore, pharmacokinetic studies on rats revealed that EQNP exhibited a 2.4-fold increase in bioavailability of etoposide than ENP with no quercetin. The developed loaded nanoparticles have the high potential to enhance the bioavailability of the etoposide and sensitize the resistant cells.

An insight into the complex cancer pathophysiology reveals that a dependable amelioration of the disease could only be envisaged with a multipronged treatment approach. It is highly evident that singular chemotherapeutic agents used in clinical practice have shown limitations like severe side effects, MDR and are often associated with poor QOL while combinations of drugs have yielded better therapeutic outcomes. The current hypothesis takes it a step forward wherein a chemotherapeutic agent is combined with a natural chemosensitizer, both loaded into a nanopotentiated particulate system, which would eventually deliver the drug cargo at the target site with certitude. The encapsulated natural bioactive would then favorably act on the tumor milieu through multiple portals and chemosensibilize the cells towards cytotoxic action of the synthetic drug moiety. This 2C (chemotherapeutic and chemosensitizer) approach along with nanosystem's attributes like high payload, prolonged action and diminished side effects would proffer a more dependable treatment modality. In conclusion, the proposed system would be a value addition to the currently available armamentarium of cancer treatment tools., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Epirubicin (EPI) is an anthracycline antineoplastic agent, commercially available for intravenous administration only and its oral ingestion continues to remain a challenge. Present investigation is aimed at the development of poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) for oral bioavailability enhancement of epirubicin. Developed formulation revealed particle size, 235.3±15.12 nm, zeta potential, -27.5±0.7 mV and drug content (39.12±2.13 μg/mg), with spherical shape and smooth surface. Cytotoxicity studies conducted on human breast adenocarcinoma cell lines (MCF-7) confirmed the superiority of epirubicin loaded poly-lactic-co-glycolic acid nanoparticles (EPI-NPs) over free epirubicin solution (EPI-S). Further, flow cytometric analysis demonstrated improved drug uptake through EPI-NPs and elucidated the dominance of caveolae mediated endocytosis for nanoparticles uptake. Transport study accomplished on human colon adenocarcinoma cell line (Caco-2) showed 2.76 fold improvement in permeability for EPI-NPs as compared to EPI-S (p<0.001) whereas a 4.49 fold higher transport was observed on rat ileum; a 1.8 fold higher (p<0.01) in comparison to Caco-2 cell lines which confirms the significant role of Peyer's patches in absorption enhancement. Furthermore, in vivo pharmacokinetic studies also revealed 3.9 fold improvement in oral bioavailability of EPI through EPI-NPs. Henceforth, EPI-NPs is a promising approach to replace pre-existing intravenous therapy thus providing "patient care at home"., (Copyright © 2015. Published by Elsevier B.V.)

The present work describes the preparation of sterically stabilize polymeric nanoparticles of mitoxantrone dihydrochloride (MTO) along with an efflux transporter (Pgp/BCRP) inhibitor that enhance the circulation time of nanoparticles and simultaneously surmount the problem of multidrug resistance (MDR). Mitoxantrone dihydrochloride being hydrophilic in nature had very low entrapment efficiency (%E.E.), thus in order to further enhance the lipophilicity and the %E.E., it was complexed with sodium deoxycholate (SDC) and this MTO-SDC-complex was used to formulate nanoparticles with/without Pgp/BCRP inhibitor by nanoprecipitation technique and was characterized for various in vitro and in vivo attributes. In vitro cell line studies were conducted on MCF7, A2780(p) and A2780(adr) cells. Furthermore, the targeting potential of hyaluronic acid (HA) coated nanoparticles for CD44 receptors was investigated using the MCF7 cell line. A reduction in the IC50 value observed with the inhibitor loaded nanoparticles in different cell lines indicated the BCRP/Pgp inhibiting ability of the formulated nanoparticles. The reduced macrophage uptake and the increased residence time in blood demonstrated the long circulating behaviour of the nanoparticles. The enhanced cellular uptake of HA coated nanoparticles in MCF7 cells revealed their targeting potential. The HA coated nanoparticles along with efflux transporter inhibitor exhibits a great potential for targeted chemotherapy in CD44 overexpressing MDR breast cancer., (Copyright © 2014. Published by Elsevier B.V.)

The dual drug loaded poly(dl-lactic-co-glycolic acid) (PLGA(1)) nanoparticles (TOP-TAM NPs(2)) concurrently delivering topotecan hydrochloride (TOP(3)) and tamoxifen citrate (TAM(4)) were developed to achieve synergism for the treatment of breast cancer by enhancing the permeation of TOP through the gut and the cells present in the breast. TAM acted as P-glycoprotein (P-gp(5)) inhibitor, reduced the side effects of individual drugs by reducing the dose. The NPs were prepared by double emulsion (w/o/w) method. The optimized TOP-TAM NPs were found to have smooth and spherical morphology by using SEM(6) and TEM(7) technique. Similarly size of nanoparticles was found to be 151.2 ± 1.6 nm with 0.147 ± 0.03 polydispersity index (PDI(8)). The percentage entrapment efficiency of 95.17 ± 3.57 and 57.77 ± 2.2 was found for TAM and TOP respectively. The lyophillized nanoparticles under DSC(9) showed amorphous nature of both TOP and TAM. In an in vitro release study the release of drugs from TOP-TAM NPs was found to follow the Higuchi pattern. The ex vivo gut permeation study revealed that the TAM enhanced the permeation of TOP and increased its bioavailability by 1.9 folds. The permeation and activity of combination of drugs were further confirmed by carrying out cell line studies on MCF-7 cells., (Copyright © 2014 Elsevier B.V. All rights reserved.)

An ultra high performance liquid chromatography-electrospray ionization-synapt mass spectrometric method (UHPLC/ESI-QTOF-MS/MS) for the analysis of curcumin (Cur), demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC) in Wistar rat brain homogenate was developed and validated. The chromatographic separation was achieved on a Waters ACQUITY UPLC™ BEH C18 (2.1mm × 100 mm; 1.7μm) column using isocratic mobile phase, consisting of acetonitrile: 10mM ammonium formate: formic acid (90:10:0.05v/v/v), at a flow rate of 0.2 ml min(-1) . The transitions occurred at m/z 367.0694/217.0598, 337.0717/173.0910, 307.0760/187.0844 for Cur, DMC, BDMC and m/z 307.0344/229.0677 for the IS (Nimesulide) respectively. The recovery of the analytes from Wistar rat brain homogenate was optimized using liquid-liquid extraction technique (LLE) in (ethyl acetate: chloform) mixture. The total run time was 3.0 min and the elution of Cur, DMC, BDMC occurred at 1.6, 1.75, 1.70 min, and for the IS 1.87 min, respectively. The linear dynamic range was established over the concentration range of 1.00 ng mL(-1) to 1000.0 ng mL(-1) (r(2) ; 0.9909 ± 0.0011, 0.9911 ± 0.003, and 0.9919 ± 0.0013) for Cur, DMC, and BDMC, respectively. The intra and inter-assay accuracy in terms of % CV for Cur, DMC, and BDMC was in the range 0.47-2.20, 0.47-1.65, and0.44-2.70, respectively. The lower limit of detection (LOD) and quantitation (LOQ) for Cur, DMC, and BDMC were 0.46, 0.05, 0.16 ng mL(-1) and 0.153, 0.015, 0.052 ng mL(-1) , respectively. Analytes were stable and the method proved to be accurate (recovery, >85%), specific and was applied to evaluate the Cur, DMC, BDMC loaded PNIPAM NPs as vehicles for nose to brain drug delivery., (Copyright © 2013 John Wiley & Sons, Ltd.)

Oxidative stress and inflammatory damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The development of new strategies for enhancing drug delivery to the brain is of great importance in diagnostics and therapeutics of central nervous diseases. The present study examined the hypothesis that intranasal delivery of nanoformulation of curcuminoids would reduce oxidative stress-associated brain injury after middle cerebral artery occlusion (MCAO). The rats were subjected to 2 h of MCAO followed by 22 h reperfusion, after which the grip strength, locomotor activity was performed. The effects of treatment in the rats were assessed by grip strength, locomotor activity and biochemical studies (glutathione peroxidase, glutathione reductase, lipid peroxidation, superoxide dismutase, and catalase) in the brain. Pretreatment with polymeric N-isopropyl acryl amide (PNIPAM) nanoparticles formulation of all three curcuminoids (curcumin (Cur), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC)) at doses (100 μg/kg body weight) given intranasally was effective in bringing significant changes on all the parameters. While nanoformulation of curcumin at a dose of 100 μg/kg body weight was most active in the treatment of cerebral ischemia as compared to others nanoformulation of curcuminoids. The potency of antioxidant activity significantly decreased in the order of PNIPAM nanoformulation of Cur > DMC >> BDMC, thus suggesting the critical role of methoxy groups on the phenyl ring.

This research aims to formulate and characterize solid lipid nanoparticles (SLNs) of Thymoquinone (THQ-SLNs) for the effective treatment of liver cirrhosis. Formulations were prepared using solvent injection method and optimized by the Box-Behnken experimental design to get the desired particle size having maximized entrapment efficiency as well as percentage release. Optimized THQ-SLNs (ST-1) with appropriate characteristics (particle size=166.1±10.96 nm; zeta potential=-11.34±3.54 mV; entrapment efficiency=71.60±3.85%; maximum % release=70.95±2.47%) were fabricated. DSC and XRD studies were carried out which collectively proved the reduced crystallinity and stability enhancing effect of the SLNs. Improved drug stability was further established by the subjection of the THQ-SLNs to accelerated stability studies (as per ICH guidelines) in contrast to the THQ-suspension. In vivo studies revealed a nearly 5 fold increase in the bioavailability of ST-1 (AUC(0→∞)=2998.91±260.503 μg/mL/h) as compared to THQ suspension (AUC(0→∞)=484.23±21.755 μg/mL/h). Pharmacodynamic data exhibited a significant decrease in the serum biomarker enzymes (SGOT, SGPT and ALP) after oral administration of THQ-SLNs as compared to control and marketed (SILYBON(®)) formulations against paracetamol (PCM)-induced liver cirrhosis. The effect of the treatment was confirmed by the histopathology of the liver microtome sections., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Ropinirole, a recent introduction in the clinical treatment of Parkinson's disease, suffers with the problems of low oral bioavailability and frequent dosing. An effective transdermal nano-emulsion drug delivery system can however resolve these issues effectively with greater therapeutic benefits and clinical significance. Therefore, the present work focuses precisely on pharmacokinetic, biochemical and mechanistic assessment of transdermal nanoemulsion gel in rats induced with Parkinson lesioned brain by 6-OHDA. DSC and FT-IR studies showed that NEG affects the normal lipid packing of stratum corneum to enhance the drug permeation. Study of pharmacokinetic parameters (AUC, C(max), and T(max)) revealed a greater and more extended release of ropinirole from nanoemulsion gel compared to that from a conventional gel (RPG) and oral marketed tablet (Ropitor). The AUC(0→∞) for RPCNG and RPTNG was found to be 928.07 ± 206.5 and 1055.99 ± 251.7 ngh/mL, respectively in comparison to 137.25 ± 31.3 and 467.15 ± 106.1 ngh/mL for RPG and oral tablet, respectively. The relative bioavailability of ropinirole has been enhanced more than two fold by RPTNG. Furthermore, antiparkinson activity was evaluated in terms of estimating the level of thiobarbituric acid reactive substances, glutathione antioxidant enzymes and catalase in lesioned brain of rats. Formulations were also found to be non-toxic and non-irritant by histological investigations., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In the recent years, there has been a growing interest in the development of nanoparticles based targeting agents for the tumor diagnostics and therapeutics. This is because of their potential to detect the tumor and treat the diseased tissue at the cellular and molecular level. In this respect nanoscale magnetic materials have shown a very promising therapeutic concept and offer a new perspective for the diagnostic and target drug delivery approach. The magnetic nanocarriers have the ability to accumulate at any desired pharmacological site just by the guidance of external magnetic field. But, the interactions of these magnetic nanocarriers with the biological environment are rare and depend largely upon their surface chemistry and size. To increase the interactions and achieve the desired pharmaceutically acceptable delivery system, the surface of magnetic nanocarriers is modified in various ways by coating with organic polymers and inorganic metals or oxides. On the basis of surface characteristics, a number of effective magnetically driven therapies have been proposed by many researchers and protected through patents time to time.

Despite the ongoing extensive research, cancer therapeutics still remains an area with unmet needs which is hampered by shortfall in the development of newer medicines. The present study discusses a nano-based combinational approach for treating solid tumor. Dual-loaded nanoparticles encapsulating gemcitabine HCl (GM) and simvastatin (SV) were fabricated by double emulsion solvent evaporation method and optimized. Optimized nanoparticles showed a particle size of 258 ± 2.4 nm, polydispersity index of 0.32 ± 0.052, and zeta potential of −12.5 mV. The size and the morphology of the particles wee further confirmed by transmission electron microscopy (TEM) and scanning electron microscopy, respectively of the particles. The entrapment efficiency of GM and SV in the nanoparticles was 38.5 ± 4.5% and 72.2 ± 5.6%, respectively. The in vitro release profile was studied for 60 h and showed Higuchi release pattern. The cell toxicity was done using MTT assay and lower IC50 was obtained with the nanoparticles as compared to the pure drug. The bioavailability of GM and SV in PLGA nanoparticles was enhanced by 1.4-fold and 1.3-fold respectively, compared to drug solution. The results revealed that co-delivery of GM and SV could be used for its oral delivery for the effective treatment of pancreatic cancer. [ABSTRACT FROM AUTHOR]

The aim of the current study was to develop a dual-loaded core shell nanoparticles encapsulating paclitaxel (PTX) and ellagic acid (EA) by membrane dialysis method. Based on particle size, polydispersity index (PDI), and entrapment efficiency, the dual drug-loaded nanoparticles (F2) was optimized. The optimized nanoparticles (F2) showed a particle size of 140±2 nm and a PDI of 0.23±3. The size and the morphology were confirmed by transmission electron microscopy (TEM) and found agreement with the results of dynamic light scattering. The entrapment efficiencies of total drug (PTX and EA), PTX, and EA in the nanoparticles (F2) were measured as 80%, 62.3%, and 37.7%, respectively. The in vitro release profile showed a controlled release pattern for 48 h. A higher cytotoxicity was observed with nanoparticles (F2) in comparison to free PTX. The results revealed that co-delivery of PTX and EA could be used for its oral delivery for the effective treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Objective: The present work aims to develop and validate stability indicating a novel liquid chromatography method with applicability i.e. to study the pharmacokinetics factor as well as estimate Tamoxifen (TMX) in bio-analytes, using Ultra High Pressure Liquid Chromatography/ Mass Spectrometry (UPLC-ESI-Q-TOF-MS/MS) in plasma. Methods: A bioanalytical method based on UPLC-ESI-Q-TOF-MS/MS has been developed and validated for the quantitative determination of TMX in female mice plasma using Clomiphine as an Internal Standard (IS). After Liquid-liquid extraction (LLE), analyte and IS, chromatographic separation was achieved on ACQUITY UPLC BEH C18 Waters column with dimensions; 100 mm x 2.1 mm; 1.7 µm, isocratic mobile phase (Acetonitrile:2 mM ammonium formate: 90:10; v/v), and a flow rate of 0.25 mL min-1. Results: The transitions occurred at m/z 372.1→178.1 and m/z 407.1 → 100.1 for TMX and IS, respectively. Liquidliquid extraction technique (LLE) using ethyl acetate was applied in order to optimize the recovery of analytes in mice plasma. The run and retention time of TMX were 6.0 and 2.63 minutes, respectively while the linear dynamic range established was 1.002-4001.07 ng/ml (r²>0.998 ± 0.0003). Intra-assay and inter-assay accuracy (% RSD) was found in the range; 2.43- 3.49. Conclusion: The proposed LC--MS/MS assay method is simple, rapid and sensitive for the determination of TMX in mice plasma for pharmacokinetic studies. Analytes were stable under various conditions i.e. autosampler, freeze--thaw, at room temperature, and under deep freeze conditions. [ABSTRACT FROM AUTHOR]

A stability-indicating high-performance thin-layer chromatographic (HPTLC) method was developed and validated for quantifying Itraconazole (Itz) in bulk drug, marketed formulation, and an in-house formulation comprised of lipidic-nano particle incorporated into vaginal gel. Aluminum plates precoated with silica gel 60 F-254 were used for TLC with Toulene:Ethyl acetate:Ammonia (1:5:0.1 v/v) as a mobile phase. The densitometric analysis was carried out at 266 nm using a Camag TLC scanner that generated compact spots for Itz (R f =0.77 ± 0.02). The regression analysis data for the calibration curve exhibited good linearity (r2 = 0.996 ± 0.0058). The LOD and LOQ values were found to be 14.29 ng spot−1 and 43.31 ng spot−1, respectively, while their recovery (99.65–100.23%) and precision (1.47%) were found to be satisfactory. Itraconazole was also subjected to forced stress conditions such as hydrolysis (acid and alkali), oxidation, dry and wet heat degradation, and photo degradation. The degradants were further characterized by NMR and Mass spectroscopy and compared with neat drug. Statistical analysis revealed that the developed method has potential for routine analysis of Itz in various formulations. It is well suited for quality control and study of pharmaceutical parameters such as release profile, loading, and entrapment in lipidic nanoparticle formulation. [ABSTRACT FROM AUTHOR]

The current approach involves the development of dual drug loaded nanoparticles of Paclitaxel (Pac) and Erlotinib (Erl) with subsequent thorough optimization in order to achieve sustained and simultaneous delivery of Pac and Erl. The formulation is developed to produce maximum efficacy with least side effects. The dual loaded paclitaxel and erlotinib nanoparticles (PE-NPs) were prepared by modified single emulsion method with appropriate optimization. The formulation was optimized for size, polydispersity index (PDI), zeta potential, surface morphology, encapsulation efficiency and loading capacity. The XRD and DSC results of a physical mixture and PE-NPs together confirmed that there was not any physical or chemical interaction among the drugs and polymer (PLGA). Further, the XRD and DSC analyses revealed that the crystalline forms of both drugs in PE-NPs were changed into amorphous form. The optimized PE-NPs were observed to have the particle size of 145.5 ± 3.2 nm, zeta potential of −9.3 ± 1.4 mV and PDI of 0.135 which indicated the particles to be of uniform size with optimum stability. The entrapment efficiency of paclitaxel was found to be 90.36% and that of erlotinib was found to be 62.23% from PE-NPs. PE-NPs further showed the sustained release of drugs from the particles with total release of 65.25% for paclitaxel and 74.83% for erlotinib in 120 h. Accelerated and intermediate stability studies also indicated that there was a minimal variation in size and entrapment efficiency of PE-NPs. [ABSTRACT FROM AUTHOR]

Abstract: A simple, sensitive, selective, precise and stability indicating high-performance thin-layer chromatographic method for determination of gatifloxacin both as a bulk drug and from polymeric nanoparticles was developed and validated as per the International Conference on Harmonization (ICH) guidelines. The method employed thin-layer chromatography (TLC) aluminium plates precoated with silica gel 60F-254 as the stationary phase and the mobile phase consisted of n-propanol–methanol-concentrated ammonia solution (25%) (5:1:0.9, v/v/v). This solvent system was found to give compact spots for gatifloxacin (R f value of 0.60±0.02). Densitometric analysis of gatifloxacin was carried out in the absorbance mode at 292nm. The linear regression analysis data for the calibration plots showed good linear relationship with r =0.9953 with respect to peak area in the concentration range of 400–1200ngspot−1. The mean value (±S.D.) of slope and intercept were 9.66±0.05 and 956.33±27.67, respectively. The method was validated for precision, accuracy, ruggedness and recovery. The limits of detection and quantitation were 2.73 and 8.27ngspot−1, respectively. Gatifloxacin was subjected to acid and alkali hydrolysis, oxidation, photodegradation and dry heat treatment. The drug undergoes degradation under acidic and basic conditions and upon wet and dry heat treatment. The degraded products were well separated from the pure drug. The statistical analysis proves that the developed method for quantification of gatifloxacin as bulk drug and from polymeric nanoparticles is reproducible and selective. As the method could effectively separate the drug from its degradation products, it can be employed as stability-indicating one. [Copyright &y& Elsevier]