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1.
Nat Commun ; 15(1): 3466, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658539

ABSTRACT

Thermal losses in photoelectric devices limit their energy conversion efficiency, and cyclic input of energy coupled with pyroelectricity can overcome this limit. Here, incorporating a pyroelectric absorber into a photovoltaic heterostructure device enables efficient electricity generation by leveraging spontaneous polarization based on pulsed light-induced thermal changes. The proposed pyroelectric-photovoltaic device outperforms traditional photovoltaic devices by 2.5 times due to the long-range electric field that occurs under pulse illumination. Optimization of parameters such as pulse frequency, scan speed, and illumination wavelength enhances power harvesting, as demonstrated by a power conversion efficiency of 11.9% and an incident-photon-to-current conversion efficiency of 200% under optimized conditions. This breakthrough enables reconfigurable electrostatic devices and presents an opportunity to accelerate technology that surpasses conventional limits in energy generation.

2.
Adv Sci (Weinh) ; 11(7): e2306408, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38083978

ABSTRACT

Omnidirectional photosensing is crucial in optoelectronic devices, enabling a wide field of view (wFoV) and leveraging potential applications for the Internet of Things in sensors, light fidelity, and photocommunication. The wFoV helps overcome the limitations of line-of-sight communication, and transparent photodetection becomes highly desirable as it enables the capture of optical information from various angles. Therefore, developing a photoelectric device with a 360° wFoV, ultra sensitivity to photons, power generation, and transparency is of utmost importance. This study utilizes a heterojunction of van der Waals SnS with Ga2 O3 to fabricate a transparent photovoltaic (TPV) device showing a 360° wFoV with bifacial onsite power production. SnS/Ga2 O3 heterojunction preparation consists of magnetron sputtering and is free from nanopatterning/nanostructuring to achieve the desired wFoV window device. The device exhibits a high average visible transmittance of 56%, generates identical power from bifacial illumination, and broadband fast photoresponse. Careful analysis of the device shows an ultra-sensitive photoinduced defect-modulated heterojunction and photocapacitance, revealed by the impedance spectroscopy, suggesting photon-flux driven charge diffusion. Leveraging the wFoV operation, the TPV embedded visual and speech photocommunication prototype demonstrated, aiming to help visually and auditory impaired individuals, promising an environmental-friendly sustainable future.

3.
Article in English | MEDLINE | ID: mdl-37609744

ABSTRACT

Skin cancer is a significant health burden being the fourth most common cancer globally and accounts for 6.2% of the total combined cancer cases. However, mortality rates due to skin cancer are less when compared with other cancers, but it is significantly high in the Asian population (43%). DNA mutations and environmental and genetic factors are linked with skin cancer prognosis; however, long-term exposure to ultraviolet (UV) radiation remains one of the leading factors worldwide. Sun exposure is a major environmental risk factor for skin cancers but is also an essential source of vitamin D. On the other hand, studies exploring the relationship between skin cancer risk and vitamin D show mixed, somewhat conflicting results. This study investigates the role of vitamin D and skin carcinogenesis to clarify the associations. Moreover, in addition to suppressing cancer stem cells, it has been observed that vitamin D also regulates tumor initiation and metastasis. In conclusion, the incorporation of well-designed studies on the metabolism of vitamin D from a genotypic and phenotypic perspective is required to understand the intricate mechanisms linking the role of vitamin D in skin carcinogenesis. These new findings will open up new pathways in targeting the disease and lead to novel opportunities for its treatment and cure.

4.
Comb Chem High Throughput Screen ; 25(10): 1695-1706, 2022.
Article in English | MEDLINE | ID: mdl-35718970

ABSTRACT

AIM: The aim of this study was to evaluate the efficacy of solid lipid nanoparticles of berberine against doxorubicin-induced cardiotoxicity. BACKGROUND: Berberine (Ber) is cardioprotective, but its oral bioavailability is low, and its effect on chemotherapy-induced cardiotoxicity has not been studied. OBJECTIVE: Solid lipid nanoparticles (SLNs) of berberine chloride were prepared, characterized and evaluated in vitro against doxorubicin-induced cardiomyocyte injury. METHODS: Berberine-loaded SLNs (Ber-SLNs) were synthesized using the water-in-oil microemulsion technique with tripalmitin, Tween 80 and poloxamer 407. Ber-SLNs were evaluated for preventive effect against toxicity of doxorubicin in H9c2 cells. The culture was pre-treated (24 h) with Ber (10 µM) and Ber-SLNs (1 and 10 µM), and 1 µM of doxorubicin (Dox) was added for 3 h. The cell viability assay (MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) and LDH (Lactate dehydrogenase)), levels of Creatine kinase-MB (CK-MB), Nitrite, MDA (Malondialdehyde), ROS (Reactive oxygen species) generation, and apoptotic DNA (Deoxyribonucleic acid) content were assessed. RESULTS: Ber-SLNs had a mean particle size of 13.12±1.188 nm, the zeta potential of -1.05 ± 0.08 mV, poly-dispersity index (PDI) of 0.317 ± 0.05 and entrapment efficiency of 50 ± 4.8%. Cell viability was 81 ± 0.17% for Ber-SLNs (10 µM) and 73.22 ± 0.83% for Ber (10 µM) treated cells in the MTT assay. Percentage cytotoxicity calculated from LDH release was 58.91 ± 0.54% after Dox, 40.3 ± 1.3% with Ber (10 µM) and 40.7 ± 1.3% with Ber-SLNs (1 µM) (p<0.001). Inflammation and oxidative stress markers were lower with Ber and Ber-SLNs. Attenuation of ROS generation and apoptosis of cardiomyocytes were noted on fluorescence microscopy. CONCLUSION: Ber SLNs effectively prevented doxorubicin-induced inflammation and oxidative stress in rat cardiomyocytes. The results demonstrate that microemulsion is a simple and costeffective technique to prepare Ber-SLNs, and may be considered as a drug delivery vehicle for berberine.


Subject(s)
Berberine , Animals , Apoptosis , Berberine/pharmacology , Berberine/therapeutic use , Cardiotoxicity/drug therapy , Cardiotoxicity/prevention & control , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Inflammation/chemically induced , Inflammation/drug therapy , Lipids , Liposomes , Myocytes, Cardiac , Nanoparticles , Rats , Reactive Oxygen Species
5.
ACS Appl Mater Interfaces ; 14(1): 706-716, 2022 Jan 12.
Article in English | MEDLINE | ID: mdl-34962758

ABSTRACT

If we can transparently produce energy, we may apply invisible power generators to residential architectures to supply energy without losing visibility. Transparent photovoltaic cells (TPVs) are a transparent solar technology that transmits visible light while absorbing the invisible short wavelengths, such as ultraviolet. Installing TPVs in buildings provides an on-site energy supply platform as a window-embedded power generator or color-matched solar cell installation on a building surface. The record-high power generation (10.82 mW) and photocurrent value (68.25 mA) were achieved from large-scale TPVs (25 cm2). The metal oxide heterojunction is the fundamental TPV structure. The high-performance TPVs were achieved by adopting a thin Si film between ZnO and NiO as a functional light-absorbing layer. Based on the large energy band gap of metal oxides, TPVs have a clear transmittance (43%) and good color coordinates, which ensure degrees of freedom to adopt TPV power generators in various colored structures or transparent power windows. The bidirectional feature of TPVs is ultimately desirable to maximize light utilization. TPVs can generate electric power from sunlight during the day and can also work from artificial light sources at night. In the near future, humans will acquire electric power without losing visibility with on-site energy supply platforms.

6.
J Phys Chem Lett ; 12(51): 12426-12436, 2021 Dec 30.
Article in English | MEDLINE | ID: mdl-34939813

ABSTRACT

Inspired by the brain, future computation depends on creating a neuromorphic device that is energy-efficient for information processing and capable of sensing and learning. The current computation-chip platform is not capable of self-power and neuromorphic functionality; therefore, a need exists for a new platform that provides both. This Perspective illustrates potential transparent photovoltaics as a platform to achieve scalable, multimodal sensory, self-sustainable neural systems (e.g., visual cortex, nociception, and electronic skin). We present herein a strategy to harvest solar power using a transparent photovoltaic device that provides neuromorphic functionality to implement versatile, sustainable, integrative, and practical applications. The proposed solid-inorganic heterostructure platform is indispensable for achieving a variety of biosensors, sensory systems, neuromorphic computing, and machine learning.


Subject(s)
Biosensing Techniques , Electric Power Supplies , Machine Learning , Neural Networks, Computer , Humans
7.
Nanoscale ; 13(10): 5243-5250, 2021 Mar 18.
Article in English | MEDLINE | ID: mdl-33650601

ABSTRACT

Bio-inspired electronic devices have significant potential for use in memory devices of the future, including in the context of neuromorphic computing and architecture. This study proposes a transparent heterojunction device for the artificial human visual cortex. Owing to their high transparency, such devices directly react to incoming light to mimic neurological and biological processes in the nervous system. Metal-oxide materials are applied to form a transparent heterojunction (n-type ZnO/p-type NiO) in the proposed device that also provides the photovoltaic function to realize the optic nerve system. The device also exhibits nociceptive features. Its transparent photovoltaic feature endows it with self-powered operation that ensures long-term reliability without needing to replace the power system. This self-powered and highly transparent visual electronic device can provide a route for sustainable applications of neuromorphic computing, including artificial eyes.

12.
Drug Deliv Transl Res ; 8(3): 565-579, 2018 06.
Article in English | MEDLINE | ID: mdl-29441466

ABSTRACT

To promote the specific targeting and elimination of CD44-positive cancer cells, berberine chloride (BRB)-encapsulated hyaluronic acid-grafted poly(lactic-co-glycolic acid) copolymer (BRB-d(HA)-g-PLGA) nanoparticles (NPs) were prepared. The targeted action of these NPs was compared to non-targeted BRB-loaded PLGA NPs and bulk BRB. The in vitro studies demonstrated faster release of BRB and increased cytotoxicity of BRB-d(HA)-g-PLGA NPs in Hela and MCF-7 cells in comparison to BRB-PLGA NPs and bulk BRB. The uptake of BRB-d(HA)-g-PLGA NPs was increased in case of MCF-7 cells as compared to HeLa cells owing to the higher expression of CD44 receptors on MCF-7 cells. The CD44 receptor-mediated uptake of these NPs was confirmed through competitive inhibition experiments. The in vitro results were further validated in vivo in Ehrlich Ascites Carcinoma (EAC)-bearing mice. EAC-bearing mice were injected intravenously with these NPs and the results obtained were compared with that of BRB-PLGA NPs and bulk BRB. BRB-d(HA)-g-PLGA NPs were found to significantly enhance apoptosis, sub-G1 content, life span, mean survival time, and ROS levels in EAC cells with subsequent decrease in mitochondrial membrane potential and tumor burden ion tumor-bearing mice. Taking into account the findings of in vitro and in vivo studies, the enhanced and targeted anti-tumor activity of HA-grafted PLGA copolymer-encapsulated NPs of BRB cannot be negated. Therefore, HA-grafted nanoparticle-based delivery of BRB may offer a promising and improved alternative for anti-tumor therapy.


Subject(s)
Antineoplastic Agents/administration & dosage , Berberine/administration & dosage , Carcinoma, Ehrlich Tumor/drug therapy , Hyaluronic Acid/administration & dosage , Lactic Acid/administration & dosage , Nanoparticles/administration & dosage , Polyglycolic Acid/administration & dosage , Animals , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Berberine/chemistry , Cell Line , Cell Survival/drug effects , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemistry , Drug Liberation , Endocytosis , HeLa Cells , Humans , Hyaluronan Receptors/metabolism , Hyaluronic Acid/chemistry , Lactic Acid/chemistry , MCF-7 Cells , Male , Mice , Nanoparticles/chemistry , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer
13.
Article in English | MEDLINE | ID: mdl-28607028

ABSTRACT

Despite recent advances in diagnostic and therapeutic methods in antifungal research, aspergillosis still remains a leading cause of morbidity and mortality. One strategy to address this problem is to enhance the activity spectrum of known antifungals, and we now report the first successful application of Candida antarctica lipase (CAL) for the preparation of optically enriched fluconazole analogues. Anti-Aspergillus activity was observed for an optically enriched derivative, (-)-S-2-(2',4'-difluorophenyl)-1-hexyl-amino-3-(1‴,2‴,4‴)triazol-1‴-yl-propan-2-ol, which exhibits MIC values of 15.6 µg/ml and 7.8 µg/disc in broth microdilution and disc diffusion assays, respectively. This compound is tolerated by mammalian erythrocytes and cell lines (A549 and U87) at concentrations of up to 1,000 µg/ml. When incorporated into dextran nanoparticles, the novel, optically enriched fluconazole analogue exhibited improved antifungal activity against Aspergillus fumigatus (MIC, 1.63 µg/ml). These results not only demonstrate the ability of biocatalytic approaches to yield novel, optically enriched fluconazole derivatives but also suggest that enantiomerically pure fluconazole derivatives, and their nanotized counterparts, exhibiting anti-Aspergillus activity may have reduced toxicity.


Subject(s)
Antifungal Agents/pharmacology , Aspergillosis/drug therapy , Aspergillus fumigatus/drug effects , Fluconazole/analogs & derivatives , Fluconazole/pharmacology , A549 Cells , Cell Line , Disk Diffusion Antimicrobial Tests , Fluconazole/adverse effects , Fungal Proteins/metabolism , Humans , Lipase/metabolism , Nanoparticles/chemistry
14.
Eur J Pharm Biopharm ; 105: 176-92, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27287553

ABSTRACT

Rapidly increasing malignant neoplastic disease demands immediate attention. Several dietary compounds have recently emerged as strong anti-cancerous agents. Among, Bromelain (BL), a protease from pineapple plant, was used to enhance its anti-cancerous efficacy using nanotechnology. In lieu of this, hyaluronic acid (HA) grafted PLGA copolymer, having tumor targeting ability, was developed. BL was encapsulated in copolymer to obtain BL-copolymer nanoparticles (NPs) that ranged between 140 to 281nm in size. NPs exhibited higher cellular uptake and cytotoxicity in cells with high CD44 expression as compared with non-targeted NPs. In vivo results on tumor bearing mice showed that NPs were efficient in suppressing the tumor growth. Hence, the formulation could be used as a self-targeting drug delivery cargo for the remission of cancer.


Subject(s)
Bromelains/administration & dosage , Carcinoma, Ehrlich Tumor/pathology , Drug Carriers , Hyaluronic Acid/chemistry , Lactic Acid/chemistry , Nanoparticles/chemistry , Polyglycolic Acid/chemistry , Animals , Cell Line, Tumor , Humans , Male , Mice , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Polylactic Acid-Polyglycolic Acid Copolymer , Spectroscopy, Fourier Transform Infrared
15.
Int J Nanomedicine ; 10: 6789-809, 2015.
Article in English | MEDLINE | ID: mdl-26586942

ABSTRACT

The clinical success of the applicability of tea polyphenols awaits efficient systemic delivery and bioavailability. Herein, following the concept of nanochemoprevention, which uses nanotechnology for enhancing the efficacy of chemotherapeutic drugs, we employed tea polyphenols, namely theaflavin (TF) and epigallocatechin-3-gallate (EGCG) encapsulated in a biodegradable nanoparticulate formulation based on poly(lactide-co-glycolide) (PLGA) with approximately 26% and 18% encapsulation efficiency, respectively. It was observed that TF/EGCG encapsulated PLGA nanoparticles (NPs) offered an up to ~7-fold dose advantage when compared with bulk TF/EGCG in terms of exerting its antiproliferative effects and also enhanced the anticancer potential of cisplatin (CDDP) in A549 (lung carcinoma), HeLa (cervical carcinoma), and THP-1 (acute monocytic leukemia) cells. Cell cycle analysis revealed that TF/EGCG-NPs were more efficient than bulk TF/EGCG in sensitizing A549 cells to CDDP-induced apoptosis, with a dose advantage of up to 20-fold. Further, TF/EGCG-NPs, alone or in combination with CDDP, were more effective in inhibiting NF-κB activation and in suppressing the expression of cyclin D1, matrix metalloproteinase-9, and vascular endothelial growth factor, involved in cell proliferation, metastasis, and angiogenesis, respectively. EGCG and TF-NPs were also found to be more effective than bulk TF/EGCG in inducing the cleavage of caspase-3 and caspase-9 and Bax/Bcl2 ratio in favor of apoptosis. Further, in vivo evaluation of these NPs in combination with CDDP showed an increase in life span (P<0.05) in mice bearing Ehrlich's ascites carcinoma cells, with apparent regression of tumor volume in comparison with mice treated with bulk doses with CDDP. These results indicate that EGCG and TF-NPs have superior cancer chemosensitization activity when compared with bulk TF/EGCG.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Ehrlich Tumor/drug therapy , Cisplatin/therapeutic use , Lactic Acid/chemistry , Polyglycolic Acid/chemistry , Polyphenols/therapeutic use , Tea/chemistry , Animals , Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Apoptosis/drug effects , Biflavonoids/pharmacology , Biflavonoids/therapeutic use , Carcinoma, Ehrlich Tumor/pathology , Catechin/analogs & derivatives , Catechin/pharmacology , Catechin/therapeutic use , Cell Count , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cisplatin/pharmacology , Female , Flow Cytometry , Humans , Kinetics , Mice , Mitochondria/drug effects , Mitochondria/metabolism , Nanoparticles/chemistry , Neovascularization, Pathologic/drug therapy , Neovascularization, Pathologic/pathology , Polylactic Acid-Polyglycolic Acid Copolymer , Polyphenols/pharmacology , Reactive Oxygen Species/metabolism
16.
J Biomed Nanotechnol ; 11(12): 2211-22, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26510314

ABSTRACT

The study aimed to measure the neuroprotective efficacy of caffeine-encapsulated poly(lactic-co-glycolic acid) (PLGA) nanoparticles over bulk and to delineate the mechanism of improvement in efficacy both in vitro and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinsonism. Caffeine-encapsulated PLGA nanoparticles exhibited more pronounced increase in the endurance of dopaminergic neurons, fibre outgrowth and expression of tyrosine hydroxylase (TH) and growth-associated protein-43 (GAP-43) against 1-methyl-4-phenylpyridinium (MPP+)-induced alterations in vitro. Caffeine-encapsulated PLGA nanoparticles also inhibited MPP(+)-mediated nuclear translocation of nuclear factor-kappa B (NF-κB) and augmented protein kinase B phosphorylation more potentially than bulk counterpart. Conversely, MPTP reduced the striatal dopamine and its metabolites and nigral TH immunoreactivity whereas augmented the nigral microglial activation and nigrostriatal lipid peroxidation and nitrite content, which were shifted towards normalcy by caffeine. The modulations were more evident in caffeine-encapsulated PLGA nanoparticles treated animals as compared with bulk. Moreover, the striatal caffeine and its metabolites were found to be significantly higher in caffeine-encapsulated PLGA nanoparticles-treated mice as compared with bulk. The results thus suggest that nanotization improves the protective efficacy of caffeine against MPTP-induced Parkinsonism owing to enhanced bioavailability, inhibition of the nuclear translocation of NF-κB and activation of protein kinase B phosphorylation.


Subject(s)
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects , Caffeine/chemistry , Caffeine/pharmacology , Drug Carriers/chemistry , Nanoparticles/chemistry , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/prevention & control , Active Transport, Cell Nucleus/drug effects , Animals , Biological Transport , Caffeine/metabolism , Cell Count , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Cell Survival/drug effects , Dopamine/metabolism , Dopaminergic Neurons/drug effects , Dopaminergic Neurons/metabolism , Dopaminergic Neurons/pathology , Drug Liberation , Fluorescein-5-isothiocyanate/chemistry , GAP-43 Protein/metabolism , Gene Expression Regulation/drug effects , Lactic Acid/chemistry , Lipid Peroxidation/drug effects , Male , Mice , Microglia/drug effects , Microglia/pathology , NF-kappa B/genetics , NF-kappa B/metabolism , Neuroprotective Agents/chemistry , Neuroprotective Agents/metabolism , Neuroprotective Agents/pharmacology , Nitrites/metabolism , Parkinsonian Disorders/metabolism , Parkinsonian Disorders/pathology , Phosphoproteins/metabolism , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Proto-Oncogene Proteins c-akt/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism
17.
ACS Nano ; 9(5): 4850-71, 2015 May 26.
Article in English | MEDLINE | ID: mdl-25825926

ABSTRACT

Sustained and safe delivery of dopamine across the blood brain barrier (BBB) is a major hurdle for successful therapy in Parkinson's disease (PD), a neurodegenerative disorder. Therefore, in the present study we designed neurotransmitter dopamine-loaded PLGA nanoparticles (DA NPs) to deliver dopamine to the brain. These nanoparticles slowly and constantly released dopamine, showed reduced clearance of dopamine in plasma, reduced quinone adduct formation, and decreased dopamine autoxidation. DA NPs were internalized in dopaminergic SH-SY5Y cells and dopaminergic neurons in the substantia nigra and striatum, regions affected in PD. Treatment with DA NPs did not cause reduction in cell viability and morphological deterioration in SH-SY5Y, as compared to bulk dopamine-treated cells, which showed reduced viability. Herein, we report that these NPs were able to cross the BBB and capillary endothelium in the striatum and substantia nigra in a 6-hydroxydopamine (6-OHDA)-induced rat model of PD. Systemic intravenous administration of DA NPs caused significantly increased levels of dopamine and its metabolites and reduced dopamine-D2 receptor supersensitivity in the striatum of parkinsonian rats. Further, DA NPs significantly recovered neurobehavioral abnormalities in 6-OHDA-induced parkinsonian rats. Dopamine delivered through NPs did not cause additional generation of ROS, dopaminergic neuron degeneration, and ultrastructural changes in the striatum and substantia nigra as compared to 6-OHDA-lesioned rats. Interestingly, dopamine delivery through nanoformulation neither caused alterations in the heart rate and blood pressure nor showed any abrupt pathological change in the brain and other peripheral organs. These results suggest that NPs delivered dopamine into the brain, reduced dopamine autoxidation-mediated toxicity, and ultimately reversed neurochemical and neurobehavioral deficits in parkinsonian rats.


Subject(s)
Blood-Brain Barrier/metabolism , Dopamine/chemistry , Dopamine/metabolism , Nanoparticles/chemistry , Parkinson Disease/drug therapy , Parkinson Disease/physiopathology , Animals , Cell Line, Tumor , Dopamine/adverse effects , Dopaminergic Neurons/metabolism , Drug Carriers/adverse effects , Drug Carriers/chemistry , Drug Carriers/metabolism , Drug Liberation , Humans , Lactic Acid/chemistry , Neostriatum/drug effects , Neostriatum/metabolism , Oxidation-Reduction , Oxidopamine/chemistry , Oxidopamine/pharmacology , Oxidopamine/therapeutic use , Parkinson Disease/metabolism , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Rats , Rats, Wistar , Receptors, Dopamine/metabolism , Safety , Up-Regulation/drug effects
18.
Eur J Pharm Biopharm ; 91: 35-46, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25619920

ABSTRACT

Conventional cancer chemotherapy leads to severe side effects, which limits its use. Nanoparticles (NPs) based delivery systems offer an effective alternative. Several evidences highlight the importance of Bromelain (BL), a proteolytic enzyme, as an anti-tumor agent which however has been limited due to the requirement of high doses at the tumor site. Therefore, we illustrate the development of BL loaded poly (lactic-co-glycolic acid) NPs that show enhanced anti-tumor effects compared to free BL. The formulated NPs with a mean particle size of 130.4 ± 8.81 nm exhibited sustained release of BL. Subsequent investigation revealed enhanced anti-tumor ability of NPs in 2-stage skin tumorigenesis mice model. Reduction in average number of tumors (∼ 2.3 folds), delay in tumorigenesis (∼ 2 weeks), percent tumorigenesis (∼ 4 folds), and percent mortality rate as well as a reduction in the average tumor volume (∼ 2.5 folds) in mice as compared to free BL were observed. The NPs were found to be superior in exerting chemopreventive effects over chemotherapeutic effects at 10 fold reduced dose than free BL, validated by the enhanced ability of NPs (∼ 1.8 folds) to protect the DNA from induced damage. The effects were also supported by histopathological evaluations. NPs were also capable of modulating the expression of pro-apoptotic (P53, Bax) and anti-apoptotic (Bcl2) proteins. Therefore, our findings demonstrate that developed NPs formulation could be used to improve the efficacy of chemotherapy by exerting chemo-preventive effects against induced carcinogenesis at lower dosages.


Subject(s)
Anticarcinogenic Agents/administration & dosage , Bromelains/administration & dosage , Carcinogenesis/drug effects , Drug Carriers/administration & dosage , Nanoparticles/chemistry , Plant Proteins/administration & dosage , Skin Neoplasms/prevention & control , Administration, Cutaneous , Ananas/chemistry , Animals , Anticarcinogenic Agents/chemistry , Anticarcinogenic Agents/therapeutic use , Bromelains/chemistry , Bromelains/therapeutic use , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/chemistry , Delayed-Action Preparations/therapeutic use , Drug Carriers/chemistry , Drug Carriers/therapeutic use , Drug Liberation , Drug Stability , Drug Storage , Enzyme Stability , Lactic Acid/chemistry , Male , Mice , Nanoparticles/ultrastructure , Particle Size , Plant Proteins/chemistry , Plant Proteins/therapeutic use , Plant Stems/chemistry , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Random Allocation , Skin/drug effects , Skin/pathology , Skin Neoplasms/chemically induced , Skin Neoplasms/pathology , Survival Analysis , Tumor Burden/drug effects
19.
PLoS One ; 9(2): e89124, 2014.
Article in English | MEDLINE | ID: mdl-24586539

ABSTRACT

Nanotized phytochemicals are being explored by researchers for promoting their uptake and effectiveness at lower concentrations. In this study, O-hexadecyl-dextran entrapped berberine chloride nanoparticles (BC-HDD NPs) were prepared, and evaluated for their cytoprotective efficacy in high glucose stressed primary hepatocytes and the results obtained compared with bulk berberine chloride (BBR) treatment. The nanotized formulation treated primary hepatocytes that were exposed to high glucose (40 mM), showed increased viability compared to the bulk BBR treated cells. BC-HDD NPs reduced the ROS generation by ∼ 3.5 fold during co-treatment, prevented GSH depletion by ∼ 1.6 fold, reduced NO formation by ∼ 5 fold and significantly prevented decline in SOD activity in stressed cells. Lipid peroxidation was also prevented by ∼ 1.9 fold in the presence of these NPs confirming the antioxidant capacity of the formulation. High glucose stress increased Bax/Bcl2 ratio followed by mitochondrial depolarization and activation of caspase-9/-3 confirming involvement of mitochondrial pathway of apoptosis in the exposed cells. Co- and post-treatment of BC-HDD NPs prevented depolarization of mitochondrial membrane, reduced Bax/Bcl2 ratio and prevented externalization of phosphatidyl-serine confirming their anti-apoptotic capacity in those cells. Sub-G1 phase apparent in high glucose stressed cells was not seen in BC-HDD NPs treated cells. The present study reveals that BC-HDD NPs at ∼ 20 fold lower concentration are as effective as BBR in preventing high glucose induced oxidative stress, mitochondrial depolarization and downstream events of apoptotic cell death.


Subject(s)
Apoptosis/drug effects , Berberine/chemistry , Berberine/pharmacology , Dextrans/chemistry , Glucose/adverse effects , Nanoparticles , Oxidative Stress/drug effects , Animals , Berberine/metabolism , Biological Transport , Cytoprotection/drug effects , DNA/metabolism , Dose-Response Relationship, Drug , Glutathione/metabolism , Lipid Peroxidation/drug effects , Male , Mitochondria/drug effects , Mitochondria/metabolism , Nitric Oxide/metabolism , Particle Size , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolism
20.
ACS Nano ; 8(1): 76-103, 2014 Jan 28.
Article in English | MEDLINE | ID: mdl-24467380

ABSTRACT

Neurogenesis, a process of generation of new neurons, is reported to be reduced in several neurodegenerative disorders including Alzheimer's disease (AD). Induction of neurogenesis by targeting endogenous neural stem cells (NSC) could be a promising therapeutic approach to such diseases by influencing the brain self-regenerative capacity. Curcumin, a neuroprotective agent, has poor brain bioavailability. Herein, we report that curcumin-encapsulated PLGA nanoparticles (Cur-PLGA-NPs) potently induce NSC proliferation and neuronal differentiation in vitro and in the hippocampus and subventricular zone of adult rats, as compared to uncoated bulk curcumin. Cur-PLGA-NPs induce neurogenesis by internalization into the hippocampal NSC. Cur-PLGA-NPs significantly increase expression of genes involved in cell proliferation (reelin, nestin, and Pax6) and neuronal differentiation (neurogenin, neuroD1, neuregulin, neuroligin, and Stat3). Curcumin nanoparticles increase neuronal differentiation by activating the Wnt/ß-catenin pathway, involved in regulation of neurogenesis. These nanoparticles caused enhanced nuclear translocation of ß-catenin, decreased GSK-3ß levels, and increased promoter activity of the TCF/LEF and cyclin-D1. Pharmacological and siRNA-mediated genetic inhibition of the Wnt pathway blocked neurogenesis-stimulating effects of curcumin. These nanoparticles reverse learning and memory impairments in an amyloid beta induced rat model of AD-like phenotypes, by inducing neurogenesis. In silico molecular docking studies suggest that curcumin interacts with Wif-1, Dkk, and GSK-3ß. These results suggest that curcumin nanoparticles induce adult neurogenesis through activation of the canonical Wnt/ß-catenin pathway and may offer a therapeutic approach to treating neurodegenerative diseases such as AD, by enhancing a brain self-repair mechanism.


Subject(s)
Alzheimer Disease/prevention & control , Cognition Disorders/drug therapy , Curcumin/pharmacology , Nanoparticles , Wnt Proteins/metabolism , beta Catenin/metabolism , Alzheimer Disease/metabolism , Animals , Curcumin/administration & dosage , Curcumin/therapeutic use , Disease Models, Animal , Microscopy, Electron, Transmission , Rats , Reelin Protein
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