Preparation and Characterization of Heparin-Retinoic Acid-Folic Acid Conjugates for Targeted Cancer Therapy

2010 ◽  
Vol 93-94 ◽  
pp. 324-327 ◽  
Author(s):  
Il Kyu Park ◽  
Yu Jin Kim ◽  
Kang Moo Huh ◽  
Yong Kyu Lee
Keyword(s):  
Folic Acid ◽  
Water Solubility ◽  
Drug Carrier ◽  
Ultra Violet ◽  
Proton Nuclear Magnetic Resonance ◽  
Coagulation Cascade ◽  
Cancer Drug ◽  
Great Promise ◽  
Target Cells

To make significant progress in the fight against cancer, treatment should target cells more specifically, produce fewer side effects, be easy to administer and deter tumor viability on multiple levels. We have attained dramatic in vivo tumor shrinkage and tumor vasculature disruption using a ternary biomolecular nanoparticle comprised of polymeric carrier polysaccharide heparin, anticancer drug retinoid and targeting ligand folic acid. The conjugation of retinoid and folic acid to heparin enhanced the water solubility of the drug, enabled selective targeting, and enhanced the role of heparin as anti-cancer drug carrier by eluding the coagulation cascade. This approach for targeting tumor holds great promise for treatment of various types of cancer. The folic acid linked heparin-retinoid conjugates (HFR) reactions was conjugated with ester and amide bonding which was confirmed by fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (1H-NMR). The ratio of HFR conjugates was measured with Ultra-Violet spectrometry (UV-spectrometry). The particle size of HFR nanoparticles was measured by dynamic light scattering (DLS), and transmission electron microscopy (TEM). HFR conjugates were spherical and showed a diameter range of 200-300 nm in size. The nanoparticles maintained their stability in serum condition for 48hrs and have the high potential for applications in biomedical field.

Abstract 129: Embryonic Stem Cell Derived Exosomes Revive Endogenous Repair Mechanisms In Failing Heart

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Mohsin Khan ◽  
Suresh K Verma ◽  
Alexander R Mackie ◽  
Erin Vaughan ◽  
Srikanth Garikipati ◽  
...  
Keyword(s):  
Stem Cells ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Cardiac Regeneration ◽  
Great Promise ◽  
Target Cells ◽  
Free System ◽  
Teratoma Formation

Rationale: Embryonic stem cells (ESCs) hold great promise for cardiac regeneration but are susceptible to ethical concerns, lack of autologous donors and teratoma formation. Recently, it has been observed that beneficial effects of stem cells are mediated by exosomes secreted out under various physiological conditions. ESCs have the ability to produce exosomes however their effect in the context of the heart is unknown. Objective: Determine the effect of ESC derived exosomes for cardiac repair and modulation of CPCs functions in the heart following myocardial infarction. Methods and Results: Exosomes were isolated from murine ESCs (mES Ex) or embryonic fibroblasts (MEFs) by ultracentrifugation and verified by Flotillin-1 immunoblot analysis. Induction of pluripotent markers, survival and in vitro tube formation was enhanced in target cells receiving ESC exosomes indicating therapeutic potential of mES Ex. mES Ex administration resulted in enhanced neovascularization, cardiomyocyte survival and reduced fibrosis post infarction consistent with resurgence of cardiac proliferative response. Importantly, mES Ex mediated considerable enhancement of cardiac progenitor cell (CPC) survival, proliferation and cardiac commitment concurrent with increased c-kit+ CPCs in vivo 4 weeks after mES Ex transfer. miRNA Array analysis of ESC and MEF exosomes revealed significantly high expression of miR290-295 cluster in the ESC exosomes compared to MEF exosomes. The underlying beneficial effect of mES Ex was tied to delivery of ESC miR-294 to the heart and in particular CPCs thereby promoting CPC survival and proliferation as analyzed by FACS based cell death analysis and CyQuant assay respectively. Interestingly, enhanced G1/S transition was observed in CPCs treated with miR-294 in conjunction with significant reduction of G1 phase. Conclusion: In conclusion, mES Ex provide a novel cell free system for cardiac regeneration with the ability to modulate both cardiomyocyte and CPC based repair programs in the heart thereby avoiding the risk of teratoma formation associated with ESCs.

Thermosensitive In Situ Gel Containing Luteolin Micelles is a Promising Efficient Agent for Colorectal Cancer Peritoneal Metastasis Treatment

2020 ◽  
Vol 16 (1) ◽  
pp. 54-64 ◽  
Author(s):  
Yuzhu Hu ◽  
Xiaoye Chen ◽  
Zongyuan Li ◽  
Songping Zheng ◽  
Yongzhong Cheng
Keyword(s):  
Colorectal Cancer ◽  
Drug Release ◽  
Peritoneal Metastasis ◽  
Water Solubility ◽  
Local Therapy ◽  
Cancer Drug ◽  
Poly Ethylene ◽  
Vegetables And Fruits

Luteolin (Lut) is a natural flavonoid mainly extracted from vegetables and fruits. Lut shows great anti-tumor potential in many malignant cancers, which are hindered by poor water solubility and low bioavailability. Peritoneal metastasis is a challenge for colorectal cancer treatment, usually indicating unfavorable prognosis of patients. Methoxy poly(ethylene glycol)-poly(ε-caprolactone) micelles containing Luteolin (Lut-M) and thermosensitive Pluronic®F127 coated Lut-M (Lut-M-F127) were synthesized and applied in the local therapy of colorectal cancer. Drug release study of Lut-M-F127 and Lut-M suggested extended drug release, and the release of Lut from Lut-M-F127 was slower than Lut-M. It was also proved that Lut-M-F127 could transit from solution to gel at body temperature. Moreover, both Lut-Free and Lut-M micelles were capable of inducing tumor cell apoptosis and reducing cell viability in vitro. Our results further demonstrated the therapeutic effect of Lut-M-F127 treatment was much better than that of Lut-M treatment in vivo. Lut-M-F127 has shown strong ability to promote tumor apoptosis, suppress tumor proliferation and block tumor angiogenesis. In summary, Lut-M-F127 formulation may be a very promising treatment option for peritoneal metastasis in colorectal cancer in the future.

scholarly journals Microfluidic manufacturing of different niosomes nanoparticles for curcumin encapsulation: Physical characteristics, encapsulation efficacy, and drug release

2019 ◽  
Vol 10 ◽  
pp. 1826-1832 ◽  
Author(s):  
Mohammad A Obeid ◽  
Ibrahim Khadra ◽  
Abdullah Albaloushi ◽  
Margaret Mullin ◽  
Hanin Alyamani ◽  
...  
Keyword(s):  
Water Solubility ◽  
Curcuma Longa ◽  
Average Particle Size ◽  
Ionic Surfactants ◽  
Ionic Surfactant ◽  
Target Cells ◽  
Average Particle ◽  
Microfluidic Mixing ◽  
Transmission Electron

Curcumin, a natural chemical compound found in Curcuma longa that has been used in antitumor and anti-inflammation applications, exhibits very limited water solubility and rapid in vivo degradation, which limits its clinical application. To overcome these limitations, niosome nanoparticles were prepared by microfluidic mixing for curcumin encapsulation. Niosome nanoparticles are lipid-based, and composed of non-ionic surfactants with cholesterol orientated into a membrane bilayer structure. Two different non-ionic surfactants were used and the mixing parameters were varied to optimize the characteristics of the prepared niosomes. The prepared niosomes had an average particle size of 70–230 nm depending on the type of non-ionic surfactant used and the mixing parameter. Moreover, all prepared niosomes were monodisperse with an average polydispersity index ranging from 0.07 to 0.3. All prepared niosomes were spherical as demonstrated by transmission electron microscopy. Curcumin was encapsulated with a maximum encapsulation efficiency of around 60% using Tween 85 as the non-ionic surfactant. Niosomes prepared by microfluidic mixing provided a controlled release of curcumin, as indicated by the release profile of curcumin, improving its therapeutic capability. These results demonstrate that niosomes prepared by microfluidic mixing to encapsulate curcumin are a promising delivery system to reach target cells.

scholarly journals Two Novel Palbociclib-Resorcinol and Palbociclib-Orcinol Cocrystals with Enhanced Solubility and Dissolution Rate

Pharmaceutics ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 23
Author(s):  
Chenxin Duan ◽  
Wenwen Liu ◽  
Yunwen Tao ◽  
Feifei Liang ◽  
Yanming Chen ◽  
...  
Keyword(s):  
Water Solubility ◽  
Cancer Drug ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Dissolution Rates ◽  
Intrinsic Dissolution ◽  
X Ray ◽  
Enhanced Solubility

Palbociclib (PAL) is an effective anti-breast cancer drug, but its use has been partly restricted due to poor bioavailability (resulting from extremely low water solubility) and serious adverse reactions. In this study, two cocrystals of PAL with resorcinol (RES) or orcinol (ORC) were prepared by evaporation crystallization to enhance their solubility. The cocrystals were characterized by single crystal X-ray diffraction, Hirshfeld surface analysis, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared and scanning electron microscopy. The intrinsic dissolution rates of the PAL cocrystals were determined in three different dissolution media (pH 1.0, pH 4.5 and pH 6.8), and both cocrystals showed improved dissolution rates at pH 1.0 and pH 6.8 in comparison to the parent drug. In addition, the cocrystals increased the solubility of PAL at pH 6.8 by 2–3 times and showed good stabilities in both the accelerated stability testing and stress testing. The PAL-RES cocrystal also exhibited an improved relative bioavailability (1.24 times) than PAL in vivo pharmacokinetics in rats. Moreover, the in vitro cytotoxicity assay of PAL-RES showed an increased IC50 value for normal cells, suggesting a better biosafety profile than PAL. Co-crystallization may represent a promising strategy for improving the physicochemical properties of PAL with better pharmacokinetics.

scholarly journals Paclitaxel-Loaded and Folic Acid Modified PLGA Nanomedicine with Glutathione-Response for the Treatment of Lung Cancer

2020 ◽  
Author(s):  
Zhanxia Zhang ◽  
Wang Yao ◽  
Jialiang Yao ◽  
Fangfang Qian ◽  
Zujun Que ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Folic Acid ◽  
Side Effects ◽  
Targeted Delivery ◽  
Great Promise ◽  
Stimuli Responsive ◽  
Biologically Relevant ◽  
Chemotherapy Agents

Abstract Targeted delivery and smart response of nanomedicine hold great promise to improve the therapeutic efficacy and alleviate the side effects of chemotherapy agents in cancer treatment. While a few research systems about organic nanomedicines with these properties have limited the development prospect of nanomedicines. In the present study, folic acid (FA) targeted delivery and GSH (glutathione) smart responsive nanomedicine was rationally designed for paclitaxel (PTX) delivery in the treatment of lung cancer. Compared with other stimuli responsive nanomedicines, this nano-carrier was not only sensitive to biologically relevant GSH for on demand drug release but also biodegradable into biocompatible by products after fulfilling its delivering task. The nanomedicine can firstly enter into tumor cells via FA and its receptor mediated endocytosis. After lysosomes escape, the PLGA (poly(lactic-co-glycolic acid) nanomedicine was triggered by the higher level of GSH and released its cargo in tumor microenvironment. In vitro and in vivo results revealed that the PLGA nanomedicine not only can inhibit the proliferation and promote the apoptosis of lung cancer cells greatly, but also possesses less toxic side effects when compared with free PTX. Therefore, the proposed drug delivery system demonstrates the encouraging potential for multifunctional nano-platform applicable to enhance the bioavailability and reduce the side effects of chemotherapy agents.

scholarly journals Trajectory of chemical cocktail-induced neutrophil reprogramming

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Yi Zhou ◽  
Chuijin Wei ◽  
Shumin Xiong ◽  
Liaoliao Dong ◽  
Zhu Chen ◽  
...  
Keyword(s):  
Cell Types ◽  
Lymphoid Cells ◽  
Great Promise ◽  
Target Cells ◽  
Differentiation Potential ◽  
Hematopoietic Stem ◽  
Multipotent Progenitors ◽  
First Time

AbstractHematopoietic reprogramming holds great promise for generating functional target cells and provides new angle for understanding hematopoiesis. We reported before for the first time that diverse differentiated hematopoietic cell lineages could be reprogrammed back into hematopoietic stem/progenitor cell-like cells by chemical cocktail. However, the exact cell types of induced cells and reprogramming trajectory remain elusive. Here, based on genetic tracing method CellTagging and single-cell RNA sequencing, it is found that neutrophils could be reprogrammed into multipotent progenitors, which acquire multi-differentiation potential both in vitro and in vivo, including into lymphoid cells. Construction of trajectory map of the reprogramming procession shows that mature neutrophils follow their canonical developmental route reversely into immature ones, premature ones, granulocyte/monocyte progenitors, common myeloid progenitors, and then the terminal cells, which is stage by stage or skips intermediate stages. Collectively, this study provides a precise dissection of hematopoietic reprogramming procession and sheds light on chemical cocktail-induction of hematopoietic stem cells.

scholarly journals Amphiphilic Polymeric Micelles Based on Deoxycholic Acid and Folic Acid Modified Chitosan for the Delivery of Paclitaxel

2018 ◽  
Vol 19 (10) ◽  
pp. 3132 ◽  
Author(s):  
Liang Li ◽  
Na Liang ◽  
Danfeng Wang ◽  
Pengfei Yan ◽  
Yoshiaki Kawashima ◽  
...  
Keyword(s):  
Folic Acid ◽  
Deoxycholic Acid ◽  
Polymeric Micelles ◽  
Drug Loading ◽  
Amorphous State ◽  
Spherical Shape ◽  
Water Soluble ◽  
Proton Nuclear Magnetic Resonance

The present investigation aimed to develop a tumor-targeting drug delivery system for paclitaxel (PTX). The hydrophobic deoxycholic acid (DA) and active targeting ligand folic acid (FA) were used to modify water-soluble chitosan (CS). As an amphiphilic polymer, the conjugate FA-CS-DA was synthesized and characterized by Proton nuclear magnetic resonance (1H-NMR) and Fourier-transform infrared spectroscopy (FTIR) analysis. The degree of substitutions of DA and FA were calculated as 15.8% and 8.0%, respectively. In aqueous medium, the conjugate could self-assemble into micelles with the critical micelle concentration of 6.6 × 10−3 mg/mL. Under a transmission electron microscope (TEM), the PTX-loaded micelles exhibited a spherical shape. The particle size determined by dynamic light scattering was 126 nm, and the zeta potential was +19.3 mV. The drug loading efficiency and entrapment efficiency were 9.1% and 81.2%, respectively. X-Ray Diffraction (XRD) analysis showed that the PTX was encapsulated in the micelles in a molecular or amorphous state. In vitro and in vivo antitumor evaluations demonstrated the excellent antitumor activity of PTX-loaded micelles. It was suggested that FA-CS-DA was a safe and effective carrier for the intravenous delivery of paclitaxel.

scholarly journals PEGylated Mesoporous Silica Nanoparticles (MCM-41): A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostrate Cancer Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1605
Author(s):  
Maedeh Koohi Moftakhari Esfahani ◽  
Seyed Ebrahim Alavi ◽  
Peter J. Cabot ◽  
Nazrul Islam ◽  
Emad L. Izake
Keyword(s):  
Prostate Cancer ◽  
Targeted Delivery ◽  
Water Solubility ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Carrier ◽  
Spherical Shape ◽  
Prostrate Cancer ◽  
Treat Prostate Cancer ◽  
Cytotoxicity Effects

Low water solubility and thus low bioavailability limit the clinical application of fenbendazole (FBZ) as a potential anticancer drug. Solubilizing agents, such as Mobil Composition of Matter Number 41 (MCM) as a drug carrier, can improve the water solubility of drugs. In this study, PEGylated MCM (PEG-MCM) nanoparticles (NPs) were synthesized and loaded with FBZ (PEG-MCM-FBZ) to improve its solubility and, as a result, its cytotoxicity effect against human prostate cancer PC-3 cells. The loading efficiency of FBZ onto PEG-MCM NPs was 17.2%. The size and zeta potential of PEG-MCM-FBZ NPs were 366.3 ± 6.9 nm and 24.7 ± 0.4 mV, respectively. They had a spherical shape and released the drug in a controlled manner at pH 1.2 and pH 6.2. PEG-MCM-FBZ were found to inhibit the migration of PC-3 cells, increase the cytotoxicity effects of FBZ against PC-3 cells by 3.8-fold, and were more potent by 1.4-fold, when compared to the non-PEGylated NPs. In addition, PEG-MCM-FBZ promoted the production of reactive oxygen species by 1.3- and 1.2-fold, respectively, when compared to FBZ and MCM-FBZ. Overall, the results demonstrate that PEG-MCM-FBZ NPs enhanced FBZ delivery to PC-3 cells; therefore, they have the potential to treat prostate cancer after a comprehensive in vivo study.

Design and Synthesis of a Biocompatible 1D Coordination Polymer as Anti-Breast Cancer Drug Carrier, 5-Fu: In Vitro and in Vivo Studies

2018 ◽  
Vol 10 (21) ◽  
pp. 17594-17604 ◽  
Author(s):  
Mahsa Rezaei ◽  
Alireza Abbasi ◽  
Rassoul Dinarvand ◽  
Mahmood Jeddi-Tehrani ◽  
Jan Janczak
Keyword(s):  
Breast Cancer ◽  
Coordination Polymer ◽  
Drug Carrier ◽  
In Vivo Studies ◽  
Cancer Drug ◽  
Design And Synthesis ◽  
1D Coordination Polymer

scholarly journals Chitosan overlaid Fe3O4/rGO nanocomposite for targeted drug delivery, imaging, and biomedical applications

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Viswanathan Karthika ◽  
Mohamad S. AlSalhi ◽  
Sandhanasamy Devanesan ◽  
Kasi Gopinath ◽  
Ayyakannu Arumugam ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Folic Acid ◽  
Targeted Drug Delivery ◽  
Drug Carrier ◽  
Drug Loading ◽  
Antioxidant Properties ◽  
Targeted Drug ◽  
Loading Amount

Abstract A hybrid and straightforward nanosystem that can be used simultaneously for cancer-targeted fluorescence imaging and targeted drug delivery in vitro was reported in this study. A chitosan (CS) polymer coated with reduced graphene oxide (rGO) and implanted with Fe3O4 nanoparticles was fabricated. The fundamental physicochemical properties were confirmed via FT-IR, XRD, FE-SEM, HR-TEM, XPS, and VSM analysis. The in vivo toxicity study in zebrafish showed that the nanocomposite was not toxic. The in vitro drug loading amount was 0.448 mg/mL−1 for doxorubicin, an anticancer therapeutic, in the rGO/Fe3O4/CS nanocomposite. Furthermore, the pH-regulated release was observed using folic acid. Cellular uptake and multimodal imaging revealed the benefit of the folic acid-conjugated nanocomposite as a drug carrier, which remarkably improves the doxorubicin accumulation inside the cancer cells over-express folate receptors. The rGO/Fe3O4/CS nanocomposite showed enhanced antibiofilm and antioxidant properties compared to other materials. This study's outcomes support the use of the nanocomposite in targeted chemotherapy and the potential applications in the polymer, cosmetic, biomedical, and food industries.

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