共查询到20条相似文献,搜索用时 31 毫秒
1.
Purpose
Hedgehog (Hh) and peroxisome proliferator-activated receptor gamma (PPAR-γ) are major signaling pathways involved in the pathogenesis of liver fibrosis. Since Hh inhibitor, vismodegib (GDC) and PPAR-γ agonist, rosiglitazone (RSG) have poor water solubility, our objective was to formulate biodegradable polymeric nanoparticles encapsulating GDC and RSG for treating liver fibrosis.Methods
Methoxy-polyethylene-glycol-b-poly(carbonate-co-lactide) [mPEG-b-p(CB-co-LA)] was synthesized and characterized using 1H NMR. Nanoparticles were prepared using this polymer by emulsification/solvent evaporation method to encapsulate GDC and RSG either alone or in combination. Nanoparticles were characterized for particle size, drug loading, drug release, and anti-fibrotic efficacy after tail vein injection into common bile duct ligated (CBDL) fibrotic rats.Results
mPEG-b-p(CB-co-LA) copolymer has molecular weight of 30,000 Da as determined by 1H NMR. Nanoparticles were monodisperse with a mean particle size of 120–130 nm. Drug loading was 5% and 2% w/w for GDC and RSG, respectively. Nanoparticles carrying both GDC and RSG were formulated at half of their individual drug loading. Systemic administration of drug loaded nanoparticles protected liver injury in CBDL rats by suppressing the activation of hepatic stellate cells, and decreasing inflammatory cytokines.Conclusion
Polymeric nanoparticles for co-delivery of Hh inhibitor and PPAR-γ agonist have the potential to treat liver fibrosis by intervening complex fibrotic cascade. 相似文献2.
Purpose
Preparation, optimization and in vitro evaluation of core-shell nanoparticles comprising of a hydrophilic core of BSA surrounded by a hydrophobic shell of PLGA for loading water-soluble drugs.Methods
A double emulsion method was optimized for preparation of BSA-PLGA based core-shell nanoparticles. Proof of concept for core-shell type structure was established by visual techniques like confocal microscopy and TEM. Characterization was done for particle size, encapsulation efficiency, drug loading and in vitro drug release. Cellular uptake was assessed using confocal microscopy, bio-TEM and HPLC assay, and cytotoxic activity was tested by MTT assay in MG-63 osteosarcoma cells.Results
The optimized core-shell nanoparticles showed a particle size of 243 nm (PDI-0.13) and encapsulation efficiency of 40.5% with a drug loading of 8.5% w/w. In vitro drug release studies showed a sustained release for 12 h. Cellular uptake studies indicated a rapid and efficient uptake within 2 h. TEM studies indicated that the core-shell nanoparticles were localized in cytoplasm region of the cells. Gemcitabine loaded core-shell nanoparticles showed enhanced cytotoxicity against MG-63 cells as compared to marketed formulation of gemcitabine (GEMCITE®).Conclusion
These results indicate that core-shell nanoparticles can be a good carrier system for delivering hydrophilic drugs like gemcitabine successfully to the cells with enhanced efficacy.Core-Shell Nanoparticles with a hydrophilic BSA core and hydrophobic PLGA shell for carrier system of hydrophilic drugs 相似文献
3.
Yu-Jin Jin Ubonvan Termsarasab Seung-Hak Ko Jae-Seong Shim Saeho Chong Suk-Jae Chung Chang-Koo Shim Hyun-Jong Cho Dae-Duk Kim 《Pharmaceutical research》2012,29(12):3443-3454
Purpose
Hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs) were developed for the targeted delivery of doxorubicin (DOX), and their antitumor efficacy for melanoma was evaluated.Methods
DOX-loaded HACE-based self-assembled NPs were prepared and their physicochemical properties were characterized. The in vitro cytotoxicity of HACE was measured using an MTS-based assay. The cellular uptake efficiency of DOX into mouse melanoma B16F10 cells was assessed by confocal laser scanning microscopy and flow cytometry. Tumor growth and body weight were monitored after the intratumoral and intravenous injection of DOX-loaded NPs into a B16F10 tumor-bearing mouse model.Results
DOX-loaded NPs, with a mean diameter of ~110?nm, a narrow size distribution, and high drug entrapment efficiency, were prepared. A sustained DOX release pattern was shown, and drug release was enhanced at pH 5.5 compared with pH 7.4. The cytotoxicity of HACE to B16F10 cells was negligible. It was assumed that DOX was taken up into the B16F10 cells through receptor-mediated endocytosis. A significant inhibitory effect was observed on tumor growth, without any serious changes in body weight, after the injection of DOX-loaded NPs into the B16F10 tumor-bearing mouse model.Conclusions
DOX-loaded HACE-based NPs were successfully developed and their antitumor efficacy against B16F10 tumors was demonstrated. 相似文献4.
Di Wen Deepak Chitkara Hao Wu Michael Danquah Renukadevi Patil Duane D. Miller Ram I. Mahato 《Pharmaceutical research》2014,31(10):2784-2795
Purpose
Our objective was to synthesize LHRH-conjugated amphiphilic copolymer for micellar delivery of CBDIV17, a novel antiandrogen for treating prostate cancer.Methods
LHRH-PEG-b-p(CB-co-LA) was synthesized by opening polymerization of carbonate (CB), lactide (LA), and HOOC-PEG-OH followed by conjugation with LHRH analogue. Bicalutamide analogue CBIDV17 loaded micelles were formulated by film hydration method, and characterized for critical micelle concentration (CMC), drug loading and in vitro drug release. Formulations were tested on LNCaP and C4-2 cells for cellular uptake, induction of apoptosis, viability and dowregulation of androgen receptor (AR). In vivo studies were performed in ectopic tumor bearing athymic nude mice after tail vein injection at a dose of 10 mg/kg. Tumor volume and body weight were measured for 25 days followed by immunohistochemistry (IHC) of tumor samples for Ki-67, caspase-3, and prostate specific antigen (PSA).Results
HOOC-PEG-b-p(CB-co-LA) and LHRH-PEG-b-p(CB-co-LA) were characterized by 1HNMR and used for preparing micelles, which had a mean particle size of 75.60?±?2.25 and 72.64?±?1.15 nm, respectively and CBDIV17 loading of 4.6% w/w. LHRH conjugated micelles showed higher cellular uptake, cytotoxicity, and apoptosis in LNCaP and C4-2 cells compared to non-targeted micelles. CBDIV17 loaded LHRH micelles more efficiently inhibited the proliferation and induced apoptosis of tumor cells according to Ki-67, caspase-3, and PSA expression. There was significant inhibition of tumor growth with the treatment of CBDIV17 loaded LHRH-conjugated micelles.Conclusion
These results demonstrated that LHRH-b-PEG-p(CB-co-LA) micelles have the potential for targeted delivery of CBDIV17 to treat advanced prostate cancer. 相似文献5.
A. Martínez E. Muñiz C. Teijón I. Iglesias J. M. Teijón M. D. Blanco 《Pharmaceutical research》2014,31(5):1264-1274
Purpose
In vivo evaluation of tamoxifen (TMX)-loaded folate-targeted nanoparticles prepared from a mixture of disulphide bond reduced bovine serum albumin (BSA-SH) and alginate-cysteine (ALG-CYS) as targeted delivery systems of TMX to tumour tissues.Methods
TMX in solution, TMX included into folate-nanoparticles and their non-targeted analogues were intravenously administered to nude mice carrying xenograft MCF-7 tumours. The antitumor activity of these systems was characterized in terms of tumour growth rate, histological and immunohistochemical analysis of tumour tissues and TMX biodistribution.Results
TMX-folate-attached nanoparticles caused tumour remission whereas free TMX or TMX-non-targeted nanoparticles could only stop the tumour development. The histological evaluation of tumour tissues showed that those treated with folate-conjugated systems presented the most quiescent and disorganized structures. Additionally, the lowest concentrations of TMX accumulated in non-targeted organs were also found after administration of the drug using this formulation.Conclusions
This study demonstrated that TMX-loaded folate-targeted systems were capable of reaching tumour sites, so enhancing the in vivo anticancer action of TMX, and allowing a new administration route to be applied and some of the current TMX therapy problems to be overcome. 相似文献6.
Ronak Savla Olga B. Garbuzenko Suzie Chen Lorna Rodriguez-Rodriguez Tamara Minko 《Pharmaceutical research》2014,31(12):3487-3502
Purpose
Design and synthesis of a tumor responsive nanoparticle-based system for imaging and treatment of various cancers.Methods
Manganese oxide nanoparticles (Mn3O4 NPs) were synthesized and modified with LHRH targeting peptide or anti-melanoma antibodies (cancer targeting moieties) and a MMP2 cleavable peptide (a possible chemotactic factor). Nanostructured lipid carriers (NLCs) were used to entrap the BRAF inhibitor, vemurafenib, and enhance cytotoxicity of the drug. Size distribution, stability, drug entrapment, cytotoxicity and genotoxicity of synthesized nanoparticles were studied in vitro. Enhancement of MRI signal by nanoparticles and their body distribution were examined in vivo on mouse models of melanoma, ovarian and lung cancers.Results
Uniform, stable cancer-targeted nanoparticles (PEGylated water-soluble Mn3O4 NPs and NLCs) were synthesized. No signs of cyto-,genotoxicity and DNA damage were detected for nanoparticles that do not contain an anticancer drug. Entrapment of vemurafenib into nanoparticles significantly enhanced drug toxicity in cancer cells with targeted V600E mutation. The developed nanoparticles containing LHRH and MMP2 peptides showed preferential accumulation in primary and metastatic tumors increasing the MRI signal in mice with melanoma, lung and ovarian cancers.Conclusions
The proposed nanoparticle-based systems provide the foundation for building an integrated MRI diagnostic and therapeutic approach for various types of cancer. 相似文献7.
das Neves J Michiels J Ariën KK Vanham G Amiji M Bahia MF Sarmento B 《Pharmaceutical research》2012,29(6):1468-1484
Purpose
To assess the intracellular delivery, antiretroviral activity and cytotoxicity of poly(??-caprolactone) (PCL) nanoparticles containing the antiretroviral drug dapivirine.Methods
Dapivirine-loaded nanoparticles with different surface properties were produced using three surface modifiers: poloxamer 338 NF (PEO), sodium lauryl sulfate (SLS) and cetyl trimethylammonium bromide (CTAB). The ability of nanoparticles to promote intracellular drug delivery was assessed in different cell types relevant for vaginal HIV transmission/microbicide development. Also, antiretroviral activity of nanoparticles was determined in different cell models, as well as their cytotoxicity.Results
Dapivirine-loaded nanoparticles were readily taken up by different cells, with particular kinetics depending on the cell type and nanoparticles, resulting in enhanced intracellular drug delivery in phagocytic cells. Different nanoparticles showed similar or improved antiviral activity compared to free drug. There was a correlation between increased antiviral activity and increased intracellular drug delivery, particularly when cell models were submitted to a single initial short-course treatment. PEO-PCL and SLS-PCL nanoparticles consistently showed higher selectivity index values than free drug, contrasting with high cytotoxicity of CTAB-PCL.Conclusions
These results provide evidence on the potential of PCL nanoparticles to affect in vitro toxicity and activity of dapivirine, depending on surface engineering. Thus, this formulation approach may be a promising strategy for the development of next generation microbicides. 相似文献8.
A. Martínez R. Olmo I. Iglesias J. M. Teijón M. D. Blanco 《Pharmaceutical research》2014,31(1):182-193
Purpose
Preparation and in vitro characterization of tamoxifen (TMX)-loaded folate-targeted nanoparticles based on disulfide bond reduced bovine serum albumin (BSA-SH) and BSA-SH/alginate-cysteine (BSA-SH/ALG-CYS) mixtures as drug delivery systems.Methods
Folate-nanoparticles were characterized in terms of folate content, morphology, size, zeta potential, TMX load and drug release kinetics. Additionally, cell viability and cellular uptake of nanoparticles were determined using different cancer cell lines.Results
Folic acid (FOL) was successfully attached to nanoparticles (ranging between 79 and170 μmol folate/g NP). Nanoparticles with 76–417 nm mean size were obtained and loaded with TMX (4.2–7.7 μg/mg NP). Zeta potential and drug extraction revealed major superficial placement of the drug, especially in the case of BSA/ALG-FOL systems. Drug release studies in the presence of surfactant showed a gradual release of the drug between 4–7 h. In general, low cytotoxicity of unloaded systems was found. Internalization of the systems was achieved and mediated by folate receptor, especially in the case of BSA NP-FOL. The administration of 10 μM TMX by TMX-FOL NP showed their efficacy as controlled TMX release systems.Conclusions
Promising anticancer action of these new TMX-loaded folate-targeted systems was demonstrated, allowing a new administration route to be studied in further in vivo studies in order to improve current TMX therapy. 相似文献9.
Zhao Wang Jianjun Chen Jin Wang Sunjoo Ahn Chien-Ming Li Yan Lu Vivian S. Loveless James T. Dalton Duane D. Miller Wei Li 《Pharmaceutical research》2012,29(11):3040-3052
Purpose
To evaluate abilities of 2-aryl-4-benzoyl-imidazoles (ABI) to overcome multidrug resistance (MDR), define their cellular target, and assess in vivo antimelanoma efficacy.Methods
MDR cell lines that overexpressed P-glycoprotein, MDR-associated proteins, and breast cancer resistance protein were used to evaluate ABI ability to overcome MDR. Cell cycle analysis, molecular modeling, and microtubule imaging were used to define ABI cellular target. SHO mice bearing A375 human melanoma xenograft were used to evaluate ABI in vivo antitumor activity. B16-F10/C57BL mouse melanoma lung metastasis model was used to test ABI efficacy to inhibit tumor lung metastasis.Results
ABIs showed similar potency to MDR cells compared to matching parent cells. ABIs were identified to target tubulin on the colchicine binding site. After 31?days of treatment, ABI-288 dosed at 25?mg/kg inhibited melanoma tumor growth by 69%; dacarbazine at 60?mg/kg inhibited growth by 52%. ABI-274 dosed at 25?mg/kg showed better lung metastasis inhibition than dacarbazine at 60?mg/kg.Conclusions
This new class of antimitotic compounds can overcome several clinically important drug resistant mechanisms in vitro and are effective in inhibiting melanoma lung metastasis in vivo, supporting their further development. 相似文献10.
Jinho Lee Jina Kim Victor Sukbong Hong Jong-Wook Park 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2014,22(1):1-9
Background
Nanotechnology has received great attention since a decade for the treatment of different varieties of cancer. However, there is a limited data available on the cytotoxic potential of Temozolomide (TMZ) formulations. In the current research work, an attempt has been made to understand the anti-metastatic effect of the drug after loading into PLGA nanoparticles against C6 glioma cells. Nanoparticles were prepared using solvent diffusion method and were characterized for size and morphology. Diffusion of the drug from the nanoparticles was studied by dialysis method. The designed nanoparticles were also assessed for cellular uptake using confocal microscopy and flow cytometry.Results
PLGA nanoparticles caused a sustained release of the drug and showed a higher cellular uptake. The drug formulations also affected the cellular proliferation and motility.Conclusion
PLGA coated nanoparticles prolong the activity of the loaded drug while retaining the anti-metastatic activity. 相似文献11.
Chwan-Fwu Lin Chih-Jen Wen Ibrahim A. Aljuffali Chun-Lin Huang Jia-You Fang 《Pharmaceutical research》2014,31(10):2664-2676
Purpose
Here we report the development of quantiosomes, niosomes formed from Span 60, cholesterol, and quantum dots (QDs), for achieving sensitive bioimaging and anticancer drug delivery.Methods
The nanocarriers were further modified by incorporating soy phosphatidylcholine (SPC), polyethylene glycol (PEG), or cationic surfactant to display different efficiencies. Carboplatin was used as the model drug. The cellular uptake, cytotoxicity, and migration inhibition of quantiosomes for treating melanoma cells were described. Finally, intratumoral carboplatin accumulation and in-vivo bioimaging were examined.Results
The average diameters of quantiosomes ranged between 151 and 173 nm, depending on the composition selected. Approximately 50% of the drug was entrapped in quantiosomes. Electron microscopy confirmed the bilayer structure of quantiosomes and the presence of QDs in the vesicular surface. The nanodispersions showed a significant internalization into cells, especially the cationic formulations. Quantiosomes increased cytotoxicity against melanoma by 3?~?4-fold as compared to free carboplatin. In-vivo intratumoral administration demonstrated an increased drug depot in melanoma from 6 to 10 ng/mg by SPC-loaded and PEGylated quantiosomes relative to aqueous control. In-vivo fluorescence imaging showed that quantiosomes reduced leakage of QDs from melanoma. A fluorescence signal confined in tumors could be sustained for at least 24 h. Quantiosomes also exhibited a sensitive and prolonged fluorescence in ovarian tumors.Conclusion
Niosomes containing QDs and carboplatin as a multifunctional nanosystems provide a non-expensive and efficient strategy to prolong drug retention and fluorescence signal in tumors. 相似文献12.
Xiaoming Luo Guoqing Jia Haixing Song Chaoyu Liu Guannan Wu Xiaohong Li 《Pharmaceutical research》2014,31(1):46-59
Purpose
Acid-labile nanoparticles are proposed to enhance the tumor targeting and anti-tumor therapy of hydroxycamptothecin (HCPT) in response to the acidic microenvironment within cells and tumor tissues.Methods
HCPT was entrapped into matrix polymers containing acid-labile segments and galactose moieties (PGBELA) through an electrospraying technique. The antitumor activities of HCPT-loaded nanoparticles were evaluated both on HepG2 cells and after intravenous injection into H22 tumor-bearing mice.Results
The electrosprayed nanoparticles were obtained with enhanced loading efficiency and extended release of HCPT compared with other nanoparticle preparation methods. The acid-lability and targeting capability of PGBELA nanoparticles resulted in a 5 times higher inhibitory activity after incubation in pH 6.8 media compared to that of pH 7.4. Animal studies indicated that both the blood circulation time and tumor distribution of PGBELA nanoparticles were significantly increased. HCPT/PGBELA nanoparticles indicated a superior in vivo antitumor activity and fewer side effects than other treatments on the basis of tumor growth, animal survival rate, tissue necrosis and cell apoptosis evaluation.Conclusion
Biodegradable PGBELA nanoparticles are capable of achieving site-specific drug delivery by active targeting and triggered release by acidic pH both in tumor tissues and after internalization within tumor cells, thereby providing a novel strategy for cancer treatment. 相似文献13.
Fengxi Liu Min Li Chunxi Liu Yongjun Liu Yanchao Liang Fengshan Wang Na Zhang 《Pharmaceutical research》2014,31(2):475-488
Purpose
To synthesize and evaluate the antitumor efficacy of double-targeted docetaxel (DTX)-carboxymethyl chitosan (CMCS)-PEG-NGR (DTX-CPN) conjugates that could target to CD13 over-expressed tumor neovascular endothelium cells and tumor cells.Methods
DTX was conjugated to CMCS via biodegradable linker and cNGR was applied to endow the conjugates with double targeting ability. The physiochemical properties and stability of this DTX-CPN conjugates were characterized. Cellular uptake study was carried out to evaluate the targeting ability of DTX-CPN conjugates. Cytotoxicity and apoptosis analysis were conducted to evaluate in vitro antitumor effects. In vivo antitumor efficacy was investigated in B16 murine melanoma model.Results
DTX-CPN conjugates could self-assemble into nanoparticles in water and were stable in plasma. cNGR modification could promote the cellular uptake of DTX-CPN conjugates in CD13 positive HUVEC and B16 cells, leading to more significant cytotoxicity and apoptosis effect than non-targeted conjugates. DTX-CPN conjugates also exhibited better antitumor effect than non-targeted conjugates and Duopafei® in a B16 murine melanoma model.Conclusions
Double-targeted DTX-CPN conjugates could efficiently target to tumor neovascular cells and tumor cells, and achieve good antitumor effects. DTX-CPN conjugates may be promising candidate for one-double targeting cancer therapy. 相似文献14.
Purpose
Overexpression of the androgen receptor (AR) and anti-apoptotic genes including X-linked inhibitor of apoptosis protein (XIAP) provide tumors with a proliferative advantage. Therefore, our objective was to determine whether novel antiandrogen (CBDIV17) and XIAP inhibitor based combination therapy can treat advanced prostate cancer.Methods
CBDIV17 and embelin-6g were synthesized and their effect on cell proliferation, apoptosis, cell cycle and AR and XIAP gene silencing determined.Results
CBDIV17 was more potent than bicalutamide and inhibited proliferation of C4-2 and LNCaP cells, IC50 for CBDIV17 was ??12???M and ??21???M in LNCaP and C4-2 cells, respectively, whereas bicalutamide had IC50 of ??46???M in LNCaP cells and minimal effect in C4-2 cells. CBDIV17 induced apoptosis more effectively compared to bicalutamide and significantly inhibited DNA replication. Combination of CBDIV17 and embelin resulted in supra-additive antiproliferative and apoptotic effects. Embelin downregulated AR expression and decreased androgen-mediated AR phosphorylation at Ser81. These hydrophobic drugs were solubilized using micelles prepared with polyethylene glycol-b-poly (carbonate-co-lactide) (PEG-b-p(CB-co-LA)) copolymer. Combination therapy inhibited prostate tumor growth more effectively compared to control or monotherapy in vivo.Conclusions
Our results demonstrated that CBDIV17 in combination with embelin can potentially treat advanced prostate cancer. 相似文献15.
Purpose
Determine the efficiency of cationic nanoparticles prepared by blending poly (lactide-co-glycolide; PLGA) and methacrylate copolymer (Eudragit® E100) to deliver a therapeutic gene encoding mouse interleukin-10, in vitro and in vivo.Methods
Nanoparticles prepared with PLGA and E100 were evaluated for delivery of plasmid DNA encoding mouse interleukin-10 in vitro and in vivo in mice upon intramuscular injection. Blood-glucose, serum interferon-gamma levels and histology of pancreas were studied to determine therapeutic efficacy. Histological evaluation of skeletal muscle from the injection site was performed to assess the biocompatibility of nanoparticles.Results
PLGA/E100 nanoparticles showed endosomal escape evidenced by confocal microscopy and buffering ability. Transfecting HEK293 cells with plasmid-loaded PLGA/E100 nanoparticles resulted in significantly (p?0.05) greater expression of interleukin-10 compared to PLGA nanoparticles. Mice treated with PLGA/E100 nanoparticles displayed higher serum levels of interleukin-10 and lower blood glucose levels compared to those treated with interleukin-10 plasmid alone or PLGA nanoparticles. High expression of interleukin-10 facilitated suppression of interferon-gamma levels and reduced islet infiltration. Histology of muscle showed that nanoparticles were biocompatible and did not cause chronic inflammatory response.Conclusions
Nanoparticles prepared by blending PLGA with methacrylate can efficiently and safely deliver plasmid DNA encoding mouse interleukin-10 leading to prevention of autoimmune diabetes. 相似文献16.
Purpose
To propose a simple method for the development of genipin-crosslinked casein micelles as a new delivery platform for prolonged release of alfuzosin hydrochloride.Methods
Crosslinked casein micelles entrapping alfuzosin were transformed into solid redispersible nanoparticles via spray-drying technique with no need for drying adjuvants based on the stabilizing effect of casein.Results
The nanoparticles displayed high production yields (86.99–94.63% w/w) with a reasonable drug incorporation efficiency ranged from 92.86 to 97.75%. The nanoparticles were readily reconstituted in aqueous solution with a particle size range of 122.1–260.0 nm and a zeta potential range of ?21.6 to ?36.6 mV indicating a good colloidal stability. No drug crystals were detectable in the scanning electron micrographs revealing successful encapsulation of alfuzosin into casein nanoparticles which was confirmed by differential scanning calorimetry. The nanoparticles succeeded in prolonging the drug release that could be controlled by modulating the genipin crosslinking degree. The release data showed a good fit into Higuchi release kinetics with non-Fickian type of drug diffusion.Conclusions
These results demonstrated that genipin-crosslinking combined with spray-drying technique could be used as a promising tool to develop solid redispersible casein nanoparticles with sustained drug release properties. 相似文献17.
Theodossis A. Theodossiou Zili Sideratou Maria E. Katsarou Dimitris Tsiourvas 《Pharmaceutical research》2013,30(11):2832-2842
Purpose
To develop a novel hyperbranched polymer-based nanocarrier for efficient drug delivery to cell mitochondria. Also to study for the first time the cytotoxic effect of doxorubicin via mitochondria-specific delivery system.Methods
We introduced alkyltriphenylphosphonium groups (TPP) to a poly(ethylene imine) hyperbranched polymer (PEI). We harnessed the hydrophobic assembly of these alkylTPP functionalized PEI molecules into ~100 nm diameter nanoparticles (PEI-TPP) and further encapsulated the chemotherapy agent doxorubicin (DOX), to produce the mitotropic nanoparticles PEI-TPP-DOX.Results
By administering PEI-TPP-DOX to human prostate carcinoma cells DU145, we found that: (i) PEI-TPP-DOX specifically localized at cell mitochondria as revealed by the inherent DOX fluorescence; (ii) in contrast to the slow apoptotic cell death incurred by DOX over the period of days at micromolar concentrations, PEI-TPP-DOX triggered rapid and severe cytotoxicity within few hours of incubation and at submicromolar incubation concentrations. This cytotoxicity was mainly found to be of a necrotic nature, not precluding autophagy related death pathways to a smaller extent.Conclusions
We have elaborated a versatile mitotropic nanocarrier; furthermore, using this platform, we have developed a mitochondrial-doxorubicin formulation with exceptional cytocidal properties, even in nanomolar concentrations.? 相似文献
18.
Liang Feng S. Kevin Li Hongshan Liu Chia-Yang Liu Kathleen LaSance Farzin Haque Dan Shu Peixuan Guo 《Pharmaceutical research》2014,31(4):1046-1058
Purpose
RNA nanoparticles derived from the three-way junction (3WJ) of the pRNA of bacteriophage phi29 DNA packaging motor were previously found to be thermodynamically stable. As the nanoparticles could have potential in ocular drug delivery, the objectives in the present study were to investigate the distribution of pRNA nanoparticles after subconjunctival injection and examine the feasibility to deliver the nanoparticles to the cells of cornea and retina.Methods
Alexa647-labeled pRNA nanoparticles (pRNA-3WJ and pRNA-X) and double-stranded RNA (dsRNA) were administered via subconjunctival injection in mice. Alexa647 dye was a control. Topical administration was performed for comparison. Ocular clearance of pRNA nanoparticles and dsRNA after the injection was assessed using whole-body fluorescence imaging of the eyes. The numbers of cells in the ocular tissues with nanoparticle cell internalization were determined in fluorescence microscopy of dissected eye tissues.Results
After subconjunctival injection, pRNA nanoparticles and dsRNA were observed to distribute into the eyes and cleared through the lymph. pRNA-3WJ, pRNA-X, and dsRNA were found in the cells of the conjunctiva, cornea, and sclera, but only pRNA-X was in the cells of the retina. Topical administration was not effective in delivering the nanoparticles to the eye.Conclusions
The pRNA nanoparticles were delivered to the cells in the eye via subconjunctival injection, and cell internalization was achieved in the cornea with pRNA-3WJ and pRNA-X and in the retina with pRNA-X. Only the X-shape pRNA-X could enter the retina. 相似文献19.
Mrudhula Baskaran Padmamalini Baskaran Navamoney Arulsamy Baskaran Thyagarajan 《Pharmaceutical research》2017,34(6):1255-1263
Purpose
Drugs used in the treatment of diseases can cause several unwanted systemic side effects. A site-specific drug delivery system can eliminate such consequences by delivering drugs to certain target areas of the body where therapeutic effects are required. Here we present the preparation and evaluation of magnetic nanoparticles of capsaicin, the active ingredient in chili peppers, coated with poly-L-lactide co-glycolide (PLGA), a FDA-approved biodegradable bioavailable polymer.Methods
PCMN were prepared by solvent-evaporation/coprecipitation technique and their physicochemical and pharmacological characteristics evaluated in vitro. Further, effective pain/inflammation therapeutics of PCMN in a mouse model of inflammation was also studied. We also prepared and evaluated the subcellular localization of PLGA coated fluorescence magnetic nanoparticle (PFMN) in vitro in HEK293 cells.Results
Transmission electron microscopic images of PCMN showed that the size of the nanoparticles were of the order of 10–20 nm. PCMN showed approximately 9.29% drug loading and 89.15% encapsulation efficiencies. In vitro dissolution studies showed an increased solubility of capsaicin due to the nano-size of the PCMN, while PLGA coating allowed sustained release of capsaicin in vitro. The PCMN also reduced paw edema after injection in mice, and confocal microscopy revealed the successful intracellular localization of PLGA-coated fluorescein magnetic nanoparticles in HEK293 cells.Conclusion
The PCMN provided a sustained release of capsaicin in vitro and inhibited carrageenan-induced inflammatory pain in mouse model in vivo. These data suggest that PLGA coating of capsaicin magnetic nanoparticles have the potential to be amenable for a sustained release of capsaicin to relieve pain.20.
Rinku Baishya Dipak K. Nayak Deepak Kumar Samarendu Sinha Amit Gupta Shantanu Ganguly Mita Chatterjee Debnath 《Pharmaceutical research》2016,33(11):2691-2703