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Our main aim to design and develop a novel 4-carboxy phenyl boronic acid (4-CPBA) conjugated Palbociclib (PALB) loaded pH-sensitive chitosan lipid nanoparticles (PPCL) to enhance the anti-cancer efficacy of the PALB in in-vitro cell line studies by loading into 4-CPBA conjugated chitosan lipid nanoparticles. 4-CPBA was conjugated to chitosan by carbodiimide chemistry and formation of conjugate was confirmed by 1 HNMR, ATR-FTIR spectroscopic techniques. Ionic-gelation method was used for the fabrication of PPCL and particles size, PDI, zeta potential were found to be 226.5 ± 4.3 nm, 0.271 ± 0.014 and 5.03 ± 0.42 mV. Presence of pH-sensitive biological macromolecule i.e. chitosan in the carrier system provides pH-sensitivity to PPCL and sustainedly released the drug upto 144 h. The PPCL exhibited approximately 7.2, 6.6, and 5-fold reduction in IC 50 values than PALB in MCF-7, MDA-MB-231 and 4T1 cells. Receptor blocking assay concluded that the fabricated nanoparticles were internalized into MCF-7 cells might be through sialic acid-mediated endocytosis. PPCL caused extensive mitochondrial depolarization, enhanced ROS generation, apoptosis (DAPI nuclear staining, acridine orange/ ethidium bromide dual staining), and reduced % cell migration than pure PALB. It was concluded that the hybrid lipid-polymer nanoparticles provides an optimistic approach for the treatment of breast cancer., Competing Interests: Declaration of competing interest The authors report no conflict of interest related to the manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Thrombotic vascular disorders, specifically thromboembolisms, have a significant detrimental effect on public health. Despite the numerous thrombolytic and antithrombotic drugs available, their efficacy in penetrating thrombus formations is limited, and they carry a high risk of promoting bleeding. Consequently, the current medication dosage protocols are inadequate for preventing thrombus formation, and higher doses are necessary to achieve sufficient prevention. By integrating phototherapy with antithrombotic therapy, this study addresses difficulties related to thrombus-targeted drug delivery. We developed self-assembling nanoparticles (NPs) through the optimization of a co-assembly engineering process. These NPs, called DIP-FU-PPy NPs, consist of polypyrrole (PPy), dipyridamole (DIP), and P-selectin-targeted fucoidan (FU) and are designed to be delivered directly to thrombi. DIP-FU-PPy NPs are proposed to offer various potentials, encompassing drug-loading capability, targeted accumulation in thrombus sites, near-infrared (NIR) photothermal-enhanced thrombus management with therapeutic efficacy, and prevention of rethrombosis. As predicted, DIP-FU-PPy NPs prevented thrombus recurrence and emitted visible fluorescence signals during thrombus clot penetration with no adverse effects. Our co-delivery nano-platform is a simple and versatile solution for NIR-phototherapeutic multimodal thrombus control., (© 2023. BioMed Central Ltd., part of Springer Nature.)

In this work, we tested the efficacy of yttrium oxide nanoparticles (NY), a promising antioxidant and anti-inflammatory agent, in L-arginine (L-Arg) induced chronic pancreatitis (CP) model. The nanoparticles were characterized using multiple techniques including transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (pXRD), and Energy dispersive X-ray analysis (EDX). The rats were divided into three groups: normal control, L-Arg control, L-Arg + NY (1 mg/kg). We probed the mechanistic effects of the NY by ELISA, multiplex analysis of TGF-β pathway and inflammatory cytokines and immunoblotting. NY treatment significantly reduced pancreatic oxidative-nitrosative stress. In addition, NY intervention also reduced inflammatory cytokines and chemokines resulting in the inhibition of fibrosis signaling. Further, NY treatment suppressed the TGF-β signaling and epithelial-mesenchymal transition (EMT). We conclude that NY shows potential antioxidant, anti-inflammatory, and anti-fibrotic effects against CP and associated fibrosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To assess the mechanistic effects of cerium oxide nanoparticles (CONPs) on Freund's complete adjuvant (FCA)-induced rheumatoid arthritis in rats. Methods: CONPs were characterized and evaluated in vitro (RAW 264.7 macrophages) and in vivo (FCA-induced rheumatoid arthritis model). Results: In vitro treatment with CONPs significantly reduced lipopolysaccharide-induced oxidative stress (as evident from dichlorodihydrofluorescein diacetate staining), diminished mitochondrial stress (as observed with tetraethylbenzimidazolylcarbocyanine iodide staining) and reduced superoxide radicals. In vivo , CONPs exhibited anti-rheumatoid arthritis activity, as evident from results of paw volume, x-ray, clinical scoring, levels of cytokines (IL-17, IL-1β, TNF-α and TGF-β1) and histology. Conclusion: We provide preclinical proof that CONPs may be a novel futuristic nanoparticle-based approach for therapy of rheumatoid arthritis.

Nanotechnology has been a boon for the biomedical field due to the freedom it provides for tailoring of pharmacokinetic properties of different drug molecules. Nanomedicine is the medical application of nanotechnology for the diagnosis, treatment and/or management of the diseases. Cerium oxide nanoparticles (CNPs) are metal oxide-based nanoparticles (NPs) which possess outstanding reactive oxygen species (ROS) scavenging activities primarily due to the availability of "oxidation switch" on their surface. These NP have been found to protect from a number of disorders with a background of oxidative stress such as cancer, diabetes etc. In fact, the CNPs have been found to possess the environment-dependent ROS modulating properties. In addition, the inherent catalase, SOD, oxidase, peroxidase and phosphatase mimetic properties of CNPs provide them superiority over a number of NPs. Further, chemical reactivity of CNPs seems to be a function of their surface chemistry which can be precisely tuned by defect engineering. However, the contradictory reports make it necessary to critically evaluate the potential of CNPs, in the light of available literature. The review is aimed at probing the feasibility of CNPs to push towards the clinical studies. Further, we have also covered and censoriously discussed the suspected negative impacts of CNPs before making our way to a consensus. This review aims to be a comprehensive, authoritative, critical, and accessible review of general interest to the scientific community., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Psoriasis is a chronic autoimmune skin disease characterized by hyperproliferation of keratinocytes. Wide treatment options used to treat psoriasis is associated with various adverse effects. To overcome this nanoformulation is prepared. Selenium is an essential trace element and plays major role in oxidation reduction system. Toxicity and stability limits the applications of selenium. Toxicity can be reduced and stabilized upon preparation into nanoparticles., Results: Selenium nanoparticles (SeNPs) exhibit potent apoptosis through the generation of reactive oxygen species (ROS) with cell cycle arrest. SeNPs topical gel application produced significant attenuation of psoriatic severity with the abrogation of acanthosis and splenomegaly. SeNPs reduced the phosphorylation and expressions of MAPKs, STAT3, GSK-3β, Akt along with PCNA, Ki67, and cyclin-D1., Conclusion: SeNPs inhibit various inflammation and proliferation mediated pathways and could be an ideal candidate for psoriasis therapy., Materials and Methods: SeNPs were characterized and various techniques were used to determine apoptosis and other molecular mechanisms. In vivo studies were performed by inducing psoriasis with imiquimod (IMQ). SeNPs were administered via topical route.

Clinical significance of Rutin (RUT) is limited by poor dissolution rate and low oral bioavailability. The study was designed to improve the physicochemical and therapeutic potential of the drug by formulating nanosuspension (NS) for osteoporosis. Rutin nanosuspension (RUT-NS) was prepared after screening a range of stabilizers and their combinations at a different concentration by antisolvent precipitation technique. Effect of precipitation on crystallinity (differential scanning calorimetry DSC, X-ray diffraction studies XRD), morphology (scanning electron microscopy, SEM) and chemical interaction (attenuated total reflectance fourier-transform infrared spectroscopy ATR-FTIR) were studied through biophysical techniques. An optimized nanosuspension exhibited a minimum particle size of 122.85 ± 5.02 nm with higher dissolution of RUT-NS (87. 63 ± 2.29%) as compared to pure drug (39.77 ± 2.8 6%). The enhanced intestine absorption and apparent permeability were achieved due to the improved particle size, surface area and dissolution. RUT-NS displayed greater (3 folds) AUC 0-24 h than pure drug. In vitro assays with RUT-NS depicted an increased cell proliferation, antioxidant (ROS) activity and osteocalcin production in MG-63 osteoblast cells. The augmented biochemical in vivo biomarkers and bone quality proved the protective effect of RUT-NS. The results supported RUT-NS as a potential therapy for maintaining bone health.

Chronic kidney disease (CKD) has wide prevalence globally that affects a considerable population and has renal fibrosis (RF) as a hallmark feature. RF is characterized by abnormal deposition of extracellular matrix (ECM) in the interstitial space of renal tissue. There are only few studies where nanoparticles (NPs) were used for targeting the kidney mainly due to their size-dependent constraints. Further, most of the studies have been carried out in healthy animals. As the diseased kidney becomes susceptible to accumulation of nanoparticles, we hypothesized that nanoparticles (size ∼10 nm) could reach the kidney and might provide protective effects due to their inherent properties. We investigated the protective effects of cerium oxide nanoparticles (CONPs) with promising antioxidant activity in a CKD model. We, to the best of our knowledge, are first to report that CONPs abrogated RF by inhibiting transforming growth factor-β (TGF-β) signaling and epithelial-mesenchymal transition (EMT) in a fibrotic kidney.

Aim: To investigate the effect of cerium oxide nanoparticles (nanoceria) on psoriasis. Materials & methods: Fourier transform infrared, powder x-ray diffraction and scanning electron microscopy were used to characterize nanoceria. Imiquimod (62.5 mg/mice) was used for the induction of psoriasis while nanoceria was administered/applied via multiple routes (topical gel, intraperitoneal and subcutaneous) as a therapeutic intervention once daily. Results: Nanoceria significantly attenuated splenic hypertrophy, psoriasis area severity index scoring, and lipid peroxidation. It also reduced the expression of various inflammatory and proliferation markers such as IL-17, IL-22, IL-23, Ki-67, NF-κB, COX-2 and GSK3. Conclusion: Nanoceria exerts an antipsoriatic effect by inhibiting major pathogenic immune axes namely the Th-cell mediated IL-17/IL-23 axis and by downregulating other crucial inflammatory proteins like NF-κB, COX-2 and GSK3.

Aim: Selenium nanoparticles (SeNPs) may have a potential role in treating dermal disorders due to its wide therapeutic properties, but there is a need to evaluate its toxicity in keratinocytes. The present study evaluated the molecular mechanism and mode of cell death induced by SeNPs on dermal keratinocytes. Materials & methods: SeNPs were synthesized, characterized and studied in human keratinocytes cells. Oxidative stress and mitochondrial membrane depolarization were evaluated by various techniques. Additionally, autophagy mediated apoptotic cell death was evaluated. Results: SeNPs induced oxidative stress and apoptotic cell death in keratinocytes by increasing autophagy through the formation of acidic lysosomes and autophagosomes. Conclusion: Overall, SeNPs induce the oxidative stress and autophagy mediated apoptotic cell death in human keratinocytes cells.

Oxidative stress plays a major role in acute pancreatitis (AP), leading to massive macrophage infiltration. Nanoyttria (NY) possesses potent free radical scavenging activity. As reactive oxygen species and inflammation play major role in AP, we hypothesized that NY may alleviate cerulein induced AP. NY ameliorated LPS induced oxidative stress in vitro. It reduced ROS, superoxide radical generation and restored the mitochondrial membrane potential in macrophages. Interestingly, NY reduced plasma amylase and lipase levels and attenuated the mitochondrial stress and inflammatory markers. NY suppressed the recruitment of inflammatory cells around the damaged pancreatic acinar cells. Furthermore, NY intervention perturbed the course of AP via reduction of endoplasmic reticulum (ER) stress markers (BiP, IRE1 and Ero1-Lα), and molecular chaperones (Hsp27 and Hsp70). We, to the best of our knowledge, report for first time that NY can attenuate experimental AP by restoration of mitochondrial and ER homeostasis through Nrf2/NFκB pathway modulation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Nanoparticles (NPs) serve to reduce the toxicity, enhance bioactivity, improve targeting, and provide versatile means to control the release profile of the encapsulated moiety. Among different NPs, inorganic NPs of metals like Ag, Au, Ce, Fe, Se, Ti and Zn possess a significant place owing to their unique bioactivities in nanoforms. Selenium (Se) is an essential trace element. It is incorporated into selenoproteins as selenocysteine (Sec) representing the most important part of the active center of their enzymatic activities. Many selenoproteins have oxidoreductase activity and, thus, regulate the physiological redox balance. Se has a narrow therapeutic window and the toxicity margins are very delicate whereas the nanoparticles of Se (SeNPs) possess remarkably reduced toxicity. SeNPs have been explored in various oxidative stress and inflammation mediated disorders like arthritis, cancer, diabetes and nephropathy with potential therapeutic benefits. SeNPs constitute an attractive carrier platform to ferry various drugs to the site of action. Herein we have discussed the significance of nanosizing on the pharmacological activity of Se. The role of SeNPs in pharmacological protection against various inflammatory and oxidative stress mediated conditions is presented. However, it is largely unknown how SeNPs may affect the pharmacokinetics and pharmacodynamics of selenoproteins. Most of the available studies were poorly designed without any comparison to the other Se sources. In the future, detailed studies with inclusion of an appropriate source of Se should be carried out with emphasis on understanding the role of selenoproteins in the observed pharmacological activity., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Aim: The present study was designed to probe the cardioprotective effects of nanoyttria (NY)., Materials & Methods: NY was characterized using various techniques. Isoproterenol (ISO)-induced cardiotoxicity challenged mice were treated with NY for 28 days at two doses (0.4 and 4 mg/kg, intraperitoneally)., Results: NY demonstrated free radical scavenging activity as shown by a 2,2-diphenyl-1-picrylhydrazyl assay. NY treatment showed alleviation of ISO-induced cardiotoxicity as evident from the reduction in biochemical parameters. The expression of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) showed significant decrease upon NY treatment. Histopathology and ECG showed protection in histoarchitecture and rhythm of heart, respectively. Reduction in hydroxyproline and TGF-β1 expression indicated antifibrotic activity., Conclusion: We report for the first time that NY ameliorates ISO-induced cardiac remodeling.

Aim: The present study was designed to probe the antidiabetic effects of nanoceria (NC) in Type 1 diabetes (T1DM)., Materials & Methods: NC was characterized using scanning electron microscopy, Fourier transform IR, powder x-ray diffraction and zeta sizer. Multiple low doses of streptozotocin (40 mg/kg, intraperitoneally, five consecutive days) induced Type 1 diabetic Swiss mice were treated with NC at two doses (0.2 and 2 mg/kg, ip.)., Results: NC treatment significantly reduced glucose levels and diabetogenesis to 50% (4/8 animals) at 0.2 mg/kg and 37.5% (3/8 animals) at 2.0 mg/kg doses. Cytokines (IL-6 and TNF-α; p < 0.048 at 2 mg/kg) and p65-NF-κB expression were diminished by NC treatment whereas the Nrf2 expression was enhanced by NC intervention indicating the role of modulation of NF-κB/Nrf2 pathway. NC exhibited promising superoxide dismutase 1 mimetic and anti-apoptotic activity., Conclusion: Considered together, our data establishes the antidiabetic potential of NC which may become a novel strategy to combat T1DM in the near future.

Background: The rapid progress in the application of different types of nanoparticles in various biomedical applications resulted in substantial increase in the use of these materials. The special physicochemical properties like small size and increased surface area offered by nanoparticles may pose unexpected toxicologic threats despite of offering promising biological effects., Objective: The intended as well as unintended exposure of nanoparticles to humans is a major challenge for the expanding field of nanoparticle therapy. In this review, an attempt has been made to briefly discuss the different factors affecting nanoparticle mediated toxicity, mechanism of toxicity, and interference of NPs with bioassays. A comprehensive overview has been provided for the in vitro and in vivo toxicologic assessment of NPs and what and how framing guidelines should be used for global unification of nanotoxicologic studies., Conclusion: The present review entails a discussion of the toxicity of nanoparticles along with interferences inherent to nanoparticles in toxicity studies. The lack of availability of regulatory guidelines for nanoparticles is one of the biggest issues. Our understanding of the mechanisms of NP-induced toxicity is superficial; thus, it is too early to come to a general consensus on the toxicity of NPs. There is a need, therefore, to standardize and validate the toxicity testing assays based on NPs properties., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Triple negative breast cancer (TNBC), owing to its aggressive behavior and toxicity associated with available chemotherapy; currently no suitable therapy is available. Honokiol (HNK) is a promising anticancer drug but has poor bioavailability. In the current study, we evaluated the anticancer effects of an oral Honokiol nanomicellar (NM) formulation (size range of 20-40nm) in vitro against various TNBC cells lines. Cytotoxicity, clonogenic and wound healing assays demonstrated the promising anticancer effects. In vitro Caco-2 permeability studies suggested increased absorption of Honokiol. Compared to HNK-FD, nanomicellar formulations resulted in significant increase in the oral bioavailability. C max (4.06 and 3.60-fold) and AUC (6.26 and 5.83-fold) were significantly increased in comparison to oral 40 and 80mg/kg free drug respectively. Further, anticancer effects of these formulations were studied in BALB/c nude mice transplanted with orthotopic MDA-MB-231 cell induced xenografts. After 4 weeks of daily administration of HNK-NM formulation, significant reduction in the tumor volumes and weights compared to free drug (p<0.001) treated groups was observed. Surprisingly, in some of the animals (25%), the treatment resulted in complete eradication of tumors. Increased apoptosis and antiangiogenic effect was observed in HNK-NM groups compared to free drug and untreated control animals. This is the first report demonstrating that HNK-FD possesses anticancer effects against TNBC., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim: The objective of this study was to formulate and evaluate a unique matrix mixture (nanomiemgel) of nanomicelle and nanoemulsion containing aceclofenac and capsaicin using in vitro and in vivo analyses and to compare it to a marketed formulation (Aceproxyvon)., Methods: Nanomicelles were prepared using Vitamin E TPGS by solvent evaporation method and nanoemulsion was prepared by high-pressure homogenization method. In vitro drug release and human skin permeation studies were performed and analyzed using HPLC. The efficiency of nanomiemgel as a delivery system was investigated using an imiquimod-induced psoriatic like plaque model developed in C57BL/6 mice., Results: Atomic Force Microscopy images of the samples exhibited a globular morphology with an average diameter of 200, 250 and 220 nm for NMI, NEM and NMG, respectively. Nanomiemgel demonstrated a controlled release drug pattern and induced 2.02 and 1.97-fold more permeation of aceclofenac and capsaicin, respectively than Aceproxyvon through dermatomed human skin. Nanomiemgel also showed 2.94 and 2.09-fold greater Cmax of aceclofenac and capsaicin, respectively than Aceproxyvon in skin microdialysis study in rats. The PASI score, ear thickness and spleen weight of the imiquimod-induced psoriatic-like plaque model were significantly (p<0.05) reduced in NMG treated mice compared to free drug, NEM, NMI & Aceproxyvon., Conclusion: Using a new combination of two different drug delivery systems (NEM+NMI), the absorption of the combined system (NMG) was found to be better than either of the individual drug delivery systems due to the utilization of the maximum possible paths of absorption available for that particular drug.

Aim: Psoriasis is a chronic autoimmune skin disorder with substantial negative impact on the patient's quality of life. The present study was carried out to demonstrate the efficiency of a novel topical delivery system in the transport of two siRNAs for the treatment of psoriatic-like plaques., Materials & Methods: We designed and developed a novel fusogenic nucleic acid lipid particle (F-NALP) system containing two therapeutic nucleic acids, anti-STAT3 siRNA (siSTAT3) and anti-TNF-α siRNA (siTNF-α). Novel cationic amphiphilic lipid with oleyl chains was synthesized and used in the nanocarrier system. Therapeutic efficacies of F-NALPs were assessed using an imiquimod-induced psoriatic-like plaque model., Results: Hydrodynamic size and surface potential of F-NALPs were 102 ± 6 nm and 32.14 ± 6.21 mV, respectively. F-NALPs delivered fluorescein isothiocyanate-siRNA to a skin depth of 360 µm. F-NALPs carrying siSTAT3 and siTNF-α significantly (p < 0.05) reduced expression of STAT3 and TNF-α mRNAs and IL-23 and Ki-67 proteins compared with solution, and was superior in comparison with Topgraf(®) (GlaxoSmithKline Pharmaceuticals Limited, Maharashtra, India)., Conclusion: Our observations demonstrate that F-NALPs can efficiently carry siSTAT3 and siTNF-α into the dermis and combination of the two nucleic acids can synergistically treat psoriatic-like plaques.

The purpose of the present study was to evaluate the effect of Telmisartan (Tel) and Losartan (Los) on nanoparticle intratumoral distribution and anticancer effects in lung cancer. A549 lung tumor cells were orthotopically and metastatically administered to Nu/nu mice. Fluorescent polystyrene nanoparticles (FPNPs, size ~200 nm) beads were used to study their intratumoral distribution after Tel and Los treatments. Animals were administered with FPNPs and after 2h, FPNPs intratumoral distribution was studied by fluorescent microscopy. Tel (~1.12 mg/kg) and Los (~4.5mg/kg) were administered by inhalation delivery at alternative days for 4 weeks to tumor bearing animals. Collagen-1, transforming growth factor beta 1 (TGF-β1), cleaved caspase-3, Vimentin and E-Cadherin expressions were studied by western blotting. To correlate the AT1 receptor blockage to anticancer effects, VEGF levels and microvessel densities (MVD) were quantified. Los and Tel treated group resulted in the 5.33 and 14.33 fold increase respectively in the FPNPs intratumoral distribution as compared to the controls. Tel treatment attenuated 2.23 and 1.70 fold Collagen 1 expression compared to untreated control and Los groups, respectively. Further, in Tel and Los treated groups, the TGF-β1 active levels were significantly (p<0.05) decreased. Tel (at four times less dose) was 1.89 and 1.92 fold superior in anticancer activity to Los respectively in A549 orthotopic and metastatic tumor models (p<0.05) when given by inhalation route. Tel, by virtue of its dual pharmacophoric nature could be an ideal candidate for combination therapy to improve the nanoparticle intratumoral distribution and anticancer effects., (© 2013.)

Aims: The present study reports a novel approach for enhancing the oral absorption and hypoglycemic activity of insulin via encapsulation in folate-(FA) coupled polyethylene glycol (PEG)ylated polylactide-co-glycolide (PLGA) nanoparticles (NPs; FA-PEG-PLGA NPs)., Materials & Methods: Insulin-loaded FA-PEG-PLGA NPs (size ∼260 nm; insulin loading ∼6.5% [w/w]; encapsulation efficiency: 87.0 ± 1.92%) were prepared by double-emulsion solvent evaporation method. The bioavailability and hypoglycemic activity of orally administered FA-insulin NPs were studied in diabetic rats., Results & Conclusion: FA-PEG-PLGA NPs (50 U/kg) exhibited a twofold increase in the oral bioavailability (double hypoglycemia) without any hypoglycemic shock as compared to subcutaneously administered standard insulin solution. Insulin NPs maintained a continual blood glucose level for 24 h, which, however, was transient (<8 h) in the case of subcutaneous insulin and associated with severe hypoglycemic shock. Overall, we have developed a patient-compliant, oral nanoformulation of insulin, once-daily administration of which would be sufficient to control diabetes for at least 24 h.

The present investigation consists in the development and characterization of CoQ10 loaded PLGA nanoparticles (CoQ10-NPs, size < 100 nm) by a scalable emulsion-diffusion-evaporation method. Thermal and crystallinity analysis collectively corroborated that CoQ10 was entrapped into the NPs in amorphous form. The lyophilized CoQ10-NPs were found to be stable for a period of 6 months (at room temperature). In vitro cell culture studies indicated that CoQ10-NPs significantly quenched ROS with nearly 10 fold higher efficacy than free CoQ10. Further, positively charged CoQ10-NPs were localized in two major sources of ROS generation: mitochondria and lysosomes. CoQ10-NPs showed improved oral bioavailability (4.28 times) as compared to free CoQ10. Finally remarkably higher hepatoprotective and anti-inflammatory activity of CoQ10-NPs as compared to free CoQ10 was observed due to mitigation of deleterious effects associated with the generation of free radicals. As elucidated by live noninvasive animal imaging, the higher anti-inflammatory activity of CoQ10-NPs can be attributed to significant accumulation of these NPs in the inflamed tissues., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The present investigation reports an extensive evaluation of in vitro and in vivo anticancer efficacy of orally administered doxorubicin-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Dox-NPs) in a breast cancer induced animal model. Spherically shaped Dox-NPs were prepared with an entrapment efficiency and particle size of 55.40 ± 2.30% and 160.20 ± 0.99 nm, respectively, and freeze-dried with 5% trehalose using stepwise freeze-drying. Cytotoxicity, as investigated on C127I cell line, revealed insignificant differences between the IC(50) of free Dox and Dox-NPs treated cells in the first 24 h, while higher cytotoxicity was demonstrated by Dox-NPs, following 72 h of incubation. Confocal laser scanning microscopy (CLSM) imaging corroborated that nanoparticles were efficiently localized into the nuclear region of C127I cells. The cellular uptake profile of Dox-NPs revealed both time and concentration dependent increases in the Caco-2 cell uptake as compared to the free Dox solution. Further, Dox-NPs significantly suppressed the growth of breast tumor in female Sprague-Dawley (SD) rats upon oral administration. Finally, orally administered Dox-NPs showed a marked reduction in cardiotoxicity when compared with intravenously injected free Dox as also evident by the increased level of malondialdehyde (MDA), lactate dehydrogenase (LDH), and creatine phosphokinase (CK-MB) and reduced levels of glutathione (GSH) and superoxide dismutase (SOD). The reduced cardiotoxicity of orally administered Dox-NPs was also confirmed by the major histopathological changes in the heart tissue after the treatments of intravenously injected free Dox and orally delivered Dox-NPs.

The present investigation reports on the conditions for preparation of tamoxifen loaded PLGA nanoparticles (Tmx-NPs) for oral administration. Tmx-NPs with >85% entrapment efficiency and 165.58 ± 3.81 nm particle size were prepared and freeze dried. Freeze dried Tmx-NPs were found to be stable in various simulated GIT media (pH 1.2, pH 3.5, pH 6.8, SGF & SIF). No significant changes in characteristics of Tmx-NPs were observed after 3 months accelerated stability studies. The cell viability in C127I cells was found to be relatively lower in Tmx-NP treated cells as compared to free Tmx treated cells. CLSM imaging reveled that nanoparticles were efficiently localized into the nuclear region of C127I cells. Oral bioavailability of Tmx was increased by 3.84 and 11.19 times as compared to the free Tmx citrate and Tmx base respectively, when formulated in NPs. In vivo oral antitumor efficacy of Tmx-NPs was carried out in DMBA induced breast tumor model and tumor size was reduced up to 41.56% as compared to untreated groups which showed an increase in tumor size up to 158.66%. Finally, Tmx-NPs showed the marked reduction in hepatotoxicty when compared with free Tmx citrate as evidenced by histopathological examination of liver tissue as well as AST, ALT and MDA levels. Therefore Tmx-NPs could have the significant value for the oral chronic breast cancer therapy with reduced hepatotoxicity., (Copyright © 2010 Elsevier Ltd. All rights reserved.)