Fabrication of self-assembled folate–biotin-quaternized starch nanoparticles as co-carrier of doxorubicin and siRNA

2017 ◽  
Vol 32 (5) ◽  
pp. 587-597 ◽  
Author(s):  
Liangping Li ◽  
Ruisong Tao ◽  
Mingming Song ◽  
Yue Zhang ◽  
Kuanmin Chen ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Drug Loading ◽  
Weight Ratio ◽  
Average Diameter ◽  
Esterification Reaction ◽  
One Pot ◽  
Starch Nanoparticles ◽  
Self Assembled

In this paper, the starch was firstly modified by quaternary reagent to obtain cationic starch. Then self-assembled folate–biotin-quaternized starch nanoparticles were prepared by a one-pot synthesis via N,N′-dicyclohexylcarbodiimide/N-hydroxysuccinimide/4-dimethylaminopyridine-mediated esterification reaction. The physicochemical properties of the prepared folate–biotin-quaternized starch nanoparticles were characterized. The average diameter of folate–biotin-quaternized starch nanoparticles was 109 nm with polydispersity index of 0.183 and zeta potential of 28.59 mV. The folate–biotin-quaternized starch nanoparticles were used as co-carrier of siRNA and doxorubicin with satisfactory drug loading capacity (6.98%) and encapsulation efficiency (69.66 %), and siRNA could be efficiently encapsulated at 40/1 weight ratio of doxorubicin/folate–biotin-quaternized starch nanoparticles to siRNA. The folate–biotin-quaternized starch nanoparticles could effectively protect siRNA from degradation of serum RNAase for up to 48 h. The release characteristics of doxorubicin and siRNA from folate–biotin-quaternized starch nanoparticles were studied in different pH environment and the release behaviors of two drugs were all pH sensitive. The folate–biotin-quaternized starch nanoparticles as a potential co-carrier of anticancer agents and gene drugs was expected to achieve future practical application in vitro and in vivo.

scholarly journals Characterization and toxicity of citral incorporated with nanostructured lipid carrier

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e3916 ◽  
Author(s):  
Noraini Nordin ◽  
Swee Keong Yeap ◽  
Nur Rizi Zamberi ◽  
Nadiah Abu ◽  
Nurul Elyani Mohamad ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Anticancer Agents ◽  
Drug Loading ◽  
Cancer Drug ◽  
Nanostructured Lipid Carrier ◽  
Tem Analysis

The nanoparticle as a cancer drug delivery vehicle is rapidly under investigation due to its promising applicability as a novel drug delivery system for anticancer agents. This study describes the development, characterization and toxicity studies of a nanostructured lipid carrier (NLC) system for citral. Citral was loaded into the NLC using high pressure homogenization methods. The characterizations of NLC-citral were then determined through various methods. Based on Transmission Electron Microscope (TEM) analysis, NLC-Citral showed a spherical shape with an average diameter size of 54.12 ± 0.30 nm and a polydipersity index of 0.224 ± 0.005. The zeta potential of NLC-Citral was −12.73 ± 0.34 mV with an entrapment efficiency of 98.9 ± 0.124%, and drug loading of 9.84 ± 0.041%. Safety profile of the formulation was examined viain vitroandin vivoroutes to study its effects toward normal cells. NLC-Citral exhibited no toxic effects towards the proliferation of mice splenocytes. Moreover, no mortality and toxic signs were observed in the treated groups after 28 days of treatment. There were also no significant alterations in serum biochemical analysis for all treatments. Increase in immunomodulatory effects of treated NLC-Citral and Citral groups was verified from the increase in CD4/CD3 and CD8/CD3 T cell population in both NLC-citral and citral treated splenocytes. This study suggests that NLC is a promising drug delivery system for citral as it has the potential in sustaining drug release without inducing any toxicity.

Polyphenol-Based Paclitaxel Prodrug Self-Assembled Nanoplatform for Tumor Synergistic Therapy

2021 ◽  
Vol 17 (11) ◽  
pp. 2198-2209
Author(s):  
Guoqiang Rong ◽  
Maomao Xu ◽  
Suxin Shi ◽  
Quanjun Yao ◽  
Wei Cheng ◽  
...  
Keyword(s):  
Drug Loading ◽  
Clinical Applications ◽  
Enhanced Permeability And Retention ◽  
Therapy Effect ◽  
Low Toxicity ◽  
Self Assembled ◽  
Tumor Accumulation ◽  
High Drug Loading

With the development of nanomedicine, studies focus on self-assembled nanoplatforms to reduce the toxicity of paclitaxel (PTX), promote the immune function at low-toxicity PTX, and achieve tumor synergistic therapy. Herein, a new nanoplatform was prepared with self-assembled 5-hydroxydopamine (DA)-PTX@tannic acid (TA)-Fe3+ nanoparticles (TDPP NPs) by consolidation of targeted DA-PTX and TA with the assistance of coordination between polyphenols and Fe3+. The polyphenol-based TDPP NPs can reduce the toxicity of PTX and thereby realize the in vitro and in vivo synergistic effect against tumors. The low-toxicity TDPP NPs can enhance the expression of CD40 immune protein. Moreover, the TDPP NPs possessed a small size (52.2±4 nm), high drug loading efficiency (95%), and stable pharmacokinetics, ensuring high tumor accumulation of TDPP NPs by enhanced permeability and retention effect. Our work sheds new light on the nanoformulation of PTX with low toxicity and synergistic therapy effect, which may find clinical applications in the future.

PEG-PLGA Nanoparticle Modified by Transferrin Loading Doxorubicin: In Vitro and In Vivo Studies for Glioma

2013 ◽  
Vol 750-752 ◽  
pp. 1643-1650 ◽  
Author(s):  
Guo Dong Liu ◽  
Jin Ning Mao ◽  
Tao Sun ◽  
Zhen Jiang ◽  
Jun Dong ◽  
...  
Keyword(s):  
Mtt Assay ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Average Diameter ◽  
C6 Glioma ◽  
C6 Glioma Cells ◽  
Hplc Assay ◽  
Plga Nanoparticle

Purpose A biodegradable PEG-PLGA nanoparticle (NP) modified by transferrin (Tf) was conceived. Doxorubicin (Dox), a widely used antitumor agent, without passing through the BBB, which limited its utility on glioma, was encapsulated inside (Tf-NP-Dox). Furthermore, its therapeutic efficacy to glioma was evaluated both in vitro and in vivo. Methods Tf-NP-Dox was prepared via modified single emulsion method. Its characterization including size, Drug loading capacity (DLC), entrapment efficiency (EE), Tf number on Tf-NP-Dox surface were estimated. The antitumor efficiency in vitro was evaluated via MTT assay. The transmembrane transportation was evaluated via HPLC assay. The antitumor efficiency in vivo was assessed on C6 glioma intracranial implant rats model. Results The average diameter of Tf-NP-Dox is around 200 nm with surface Tf molecule number per Tf-NP-Dox approximately 25. MTT assay demonstrated stronger cytotoxicity of Tf-NP-Dox to C6 glioma cells (P<0.01). HPLC assay showed Tf-NP-Dox transport Dox into C6 with higher efficiency compare to NP-Dox or Dox (P<0.01). On C6 glioma bearing rat, Tf-NP-Dox could transport more Dox into tumors tested by HPLC assay (P<0.05), and extended life span markedly compared to NP-Dox or Dox (P<0.05). Conclusions Tf-NP-Dox had a potential of glioma targeting and had a better therapeutic effect to glioma both in vitro and in vivo.

Current Status and Future Perspective for Research on Medicinal Plants with Anticancerous Activity and Minimum Cytotoxic Value

2019 ◽  
Vol 20 (12) ◽  
pp. 1227-1243
Author(s):  
Hina Qamar ◽  
Sumbul Rehman ◽  
D.K. Chauhan
Keyword(s):  
Side Effects ◽  
Medicinal Plants ◽  
Anticancer Agents ◽  
Drug Targets ◽  
Psidium Guajava ◽  
Current Status ◽  
Future Perspective ◽  
Wide Range

Cancer is the second leading cause of morbidity and mortality worldwide. Although chemotherapy and radiotherapy enhance the survival rate of cancerous patients but they have several acute toxic effects. Therefore, there is a need to search for new anticancer agents having better efficacy and lesser side effects. In this regard, herbal treatment is found to be a safe method for treating and preventing cancer. Here, an attempt has been made to screen some less explored medicinal plants like Ammania baccifera, Asclepias curassavica, Azadarichta indica, Butea monosperma, Croton tiglium, Hedera nepalensis, Jatropha curcas, Momordica charantia, Moringa oleifera, Psidium guajava, etc. having potent anticancer activity with minimum cytotoxic value (IC50 >3μM) and lesser or negligible toxicity. They are rich in active phytochemicals with a wide range of drug targets. In this study, these medicinal plants were evaluated for dose-dependent cytotoxicological studies via in vitro MTT assay and in vivo tumor models along with some more plants which are reported to have IC50 value in the range of 0.019-0.528 mg/ml. The findings indicate that these plants inhibit tumor growth by their antiproliferative, pro-apoptotic, anti-metastatic and anti-angiogenic molecular targets. They are widely used because of their easy availability, affordable price and having no or sometimes minimal side effects. This review provides a baseline for the discovery of anticancer drugs from medicinal plants having minimum cytotoxic value with minimal side effects and establishment of their analogues for the welfare of mankind.

Mannose Conjugated Starch Nanoparticles for Preferential Targeting of Liver Cancer

2020 ◽  
Vol 17 ◽  
Author(s):  
Akhlesh Kumar Jain ◽  
Hitesh Sahu ◽  
Keerti Mishra ◽  
Suresh Thareja
Keyword(s):  
Side Effects ◽  
Liver Cancer ◽  
Entrapment Efficiency ◽  
Xrd Analysis ◽  
In Vitro Cytotoxicity ◽  
Physical Interaction ◽  
Scanning Calorimetry ◽  
Starch Nanoparticles

Aim: To design D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for site specific delivery. Background: Liver cancer is the third leading cause of death in world and fifth most often diagnosed cancer is the major global threat to public health. Treatment of liver cancer with conventional method bears several side effects, thus to undertake these side effects as a formulation challenge, it is necessary to develop novel target specific drug delivery system for the effective and better localization of drug into the proximity of target with restricting the movement of drug in normal tissues. Objective: To optimize and characterize the developed D-Mannose conjugated 5-Fluorouracil (5-FU) loaded Jackfruit seed starch nanoparticles (JFSSNPs) for effective treatment of liver cancer. Materials and methods: 5-FU loaded JFSSNPs were prepared and optimized formulation had higher encapsulation efficiency were conjugated with D-Mannose. These formulations were characterized for size, morphology, zeta potential, X-Ray Diffraction, and Differential Scanning Calorimetry. Potential of NPs were studied using in vitro cytotoxicity assay, in vivo kinetic studies and bio-distribution studies. Result and discussion: 5-Fluorouracil loaded NPs had particle size between 336 to 802nm with drug entrapment efficiency was between 64.2 to 82.3%. In XRD analysis, 5-FU peak was diminished in the diffractogram, which could be attributed to the successful incorporation of drug in amorphous form. DSC study suggests there was no physical interaction between 5- FU and Polymer. NPs showed sustained in vitro 5-FU release up to 2 hours. In vivo, mannose conjugated NPs prolonged the plasma level of 5-FU and assist selective accumulation of 5-FU in the liver (vs other organs spleen, kidney, lungs and heart) compared to unconjugated one and plain drug. Conclusion: In vivo, bio-distribution and plasma profile studies resulted in significantly higher concentration of 5- Fluorouracil liver suggesting that these carriers are efficient, viable, and targeted carrier of 5-FU treatment of liver cancer.

Alkaloids as Anticancer Agents: A Review of Chinese Patents in Recent 5 Years

2020 ◽  
Vol 15 (1) ◽  
pp. 2-13 ◽  
Author(s):  
Hongyu Tao ◽  
Ling Zuo ◽  
Huanli Xu ◽  
Cong Li ◽  
Gan Qiao ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Kinase Inhibitors ◽  
Protein Kinase Inhibitors ◽  
Cdk Inhibitors ◽  
Comprehensive Overview ◽  
P53 Expression ◽  
Study Results

Background: In recent years, many novel alkaloids with anticancer activity have been found in China, and some of them are promising for developing as anticancer agents. Objective: This review aims to provide a comprehensive overview of the information about alkaloid anticancer agents disclosed in Chinese patents, and discusses their potential to be developed as anticancer drugs used clinically. Methods: Anticancer alkaloids disclosed in Chinese patents in recent 5 years were presented according to their mode of actions. Their study results published on PubMed, and SciDirect databases were presented. Results: More than one hundred anticancer alkaloids were disclosed in Chinese patents and their mode of action referred to arresting cell cycle, inhibiting protein kinases, affecting DNA synthesis and p53 expression, etc. Conclusion: Many newly found alkaloids displayed potent anticancer activity both in vitro and in vivo, and some of the anticancer alkaloids acted as protein kinase inhibitors or CDK inhibitors possess the potential for developing as novel anticancer agents.

Evaluation of Pyrano[3,2 C] Quinoline Analogues as Anticancer Agents

2019 ◽  
Vol 19 (10) ◽  
pp. 1285-1292 ◽  
Author(s):  
Kuldip D. Upadhyay ◽  
Anamik K. Shah
Keyword(s):  
Anticancer Agents ◽  
Human Cancer ◽  
Biological Activities ◽  
Cytotoxic Agents ◽  
Tumor Growth Inhibition ◽  
Mice Model ◽  
One Pot ◽  
Aryl Ring ◽  
Hct 116

Background: Quinoline analogues exhibited diversified biological activities depending on the structure type. A number of natural products with pyrano[3,2-c]quinolone structural motifs and patented chromenes were reported as promising cytotoxic agents. Objective: The present study is aimed to evaluate a new series of pyrano[3,2-c]quinoline scaffolds derived from the fusion of bioactive quinolone pharmacophore with structurally diverse aryl substituted chromene for its cytotoxicity. Methods: A library of pyrano[3,2-c]quinoline analogues was prepared from one-pot multi component synthesis using various aromatic aldehydes, malononitrile and 2,4-dihydroxy-1-methylquinoline. The new synthetics were primarily screened for its cytotoxicity (IC50) against different human cancer cell lines in vitro. The promising synthetics were further evaluated in vitro for their potency against different kinase activity. The promising compounds were finally tested for their in vivo efficacy in SCID type mice HCT-116 tumor model. Results: The screening results revealed that compounds 4c, 4f, 4i and 4j showed promising activity in in vitro study. However, compound 4c was found to be the most potent candidate with 23% tumor growth inhibition in HCT-116 tumor mice model. Conclusion: The structure activity relationship suggested that 3-substitution on the aryl ring at C4 position of the pyrano[3,2 c]quinolone moiety seems to have an important position for cytotoxicity activity. However, 3- chloro substitution at C4 aryl ring showed a significant alteration of the bioactive conformer of the parent scaffold and outcome with compound 4c as the most potent candidate of the series.

scholarly journals Improved in vivo PET imaging of the adenosine A2A receptor in the brain using [18F]FLUDA, a deuterated radiotracer with high metabolic stability

2021 ◽  
Author(s):  
Thu Hang Lai ◽  
Magali Toussaint ◽  
Rodrigo Teodoro ◽  
Sladjana Dukić-Stefanović ◽  
Daniel Gündel ◽  
...  
Keyword(s):  
Specific Binding ◽  
Radiochemical Yield ◽  
Toxicity Study ◽  
In Vivo Evaluation ◽  
One Pot ◽  
Specific Binding Ratio ◽  
Mri Studies ◽  
The Brain

Abstract Purpose The adenosine A2A receptor has emerged as a therapeutic target for multiple diseases, and thus the non-invasive imaging of the expression or occupancy of the A2A receptor has potential to contribute to diagnosis and drug development. We aimed at the development of a metabolically stable A2A receptor radiotracer and report herein the preclinical evaluation of [18F]FLUDA, a deuterated isotopologue of [18F]FESCH. Methods [18F]FLUDA was synthesized by a two-step one-pot approach and evaluated in vitro by autoradiographic studies as well as in vivo by metabolism and dynamic PET/MRI studies in mice and piglets under baseline and blocking conditions. A single-dose toxicity study was performed in rats. Results [18F]FLUDA was obtained with a radiochemical yield of 19% and molar activities of 72–180 GBq/μmol. Autoradiography proved A2A receptor–specific accumulation of [18F]FLUDA in the striatum of a mouse and pig brain. In vivo evaluation in mice revealed improved stability of [18F]FLUDA compared to that of [18F]FESCH, resulting in the absence of brain-penetrant radiometabolites. Furthermore, the radiometabolites detected in piglets are expected to have a low tendency for brain penetration. PET/MRI studies confirmed high specific binding of [18F]FLUDA towards striatal A2A receptor with a maximum specific-to-non-specific binding ratio in mice of 8.3. The toxicity study revealed no adverse effects of FLUDA up to 30 μg/kg, ~ 4000-fold the dose applied in human PET studies using [18F]FLUDA. Conclusions The new radiotracer [18F]FLUDA is suitable to detect the availability of the A2A receptor in the brain with high target specificity. It is regarded ready for human application.

scholarly journals Long-Acting Risperidone Dual Control System: Preparation, Characterization and Evaluation In Vitro and In Vivo

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1210
Author(s):  
Xieguo Yan ◽  
Shiqiang Wang ◽  
Kaoxiang Sun
Keyword(s):  
Drug Loading ◽  
Entrapment Efficiency ◽  
In Vitro Dissolution ◽  
Dissolution Behavior ◽  
In Vivo Evaluation ◽  
Long Term Treatment ◽  
Long Acting

Schizophrenia, a psychiatric disorder, requires long-term treatment; however, large fluctuations in blood drug concentration increase the risk of adverse reactions. We prepared a long-term risperidone (RIS) implantation system that can stabilize RIS release and established in-vitro and in-vivo evaluation systems. Cumulative release, drug loading, and entrapment efficiency were used as evaluation indicators to evaluate the effects of different pore formers, polymer ratios, porogen concentrations, and oil–water ratios on a RIS implant (RIS-IM). We also built a mathematical model to identify the optimized formulation by stepwise regression. We also assessed the crystalline changes, residual solvents, solubility and stability after sterilization, in-vivo polymer degradation, pharmacokinetics, and tissue inflammation in the case of the optimized formulation. The surface of the optimized RIS microspheres was small and hollow with 134.4 ± 3.5 µm particle size, 1.60 SPAN, 46.7% ± 2.3% implant drug loading, and 93.4% entrapment efficiency. The in-vitro dissolution behavior of RIS-IM had zero-order kinetics and stable blood concentration; no lag time was released for over three months. Furthermore, the RIS-IM was not only non-irritating to tissues but also had good biocompatibility and product stability. Long-acting RIS-IMs with microspheres and film coatings can provide a new avenue for treating schizophrenia.

scholarly journals Development of In Situ Self-Assembly Nanoparticles to Encapsulate Lopinavir and Ritonavir for Long-Acting Subcutaneous Injection

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 904
Author(s):  
Irin Tanaudommongkon ◽  
Asama Tanaudommongkon ◽  
Xiaowei Dong
Keyword(s):  
Sustained Release ◽  
Trough Concentration ◽  
Self Assembly ◽  
Subcutaneous Injection ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Long Acting

Most antiretroviral medications for human immunodeficiency virus treatment and prevention require high levels of patient adherence, such that medications need to be administered daily without missing doses. Here, a long-acting subcutaneous injection of lopinavir (LPV) in combination with ritonavir (RTV) using in situ self-assembly nanoparticles (ISNPs) was developed to potentially overcome adherence barriers. The ISNP approach can improve the pharmacokinetic profiles of the drugs. The ISNPs were characterized in terms of particle size, drug entrapment efficiency, drug loading, in vitro release study, and in vivo pharmacokinetic study. LPV/RTV ISNPs were 167.8 nm in size, with a polydispersity index of less than 0.35. The entrapment efficiency was over 98% for both LPV and RTV, with drug loadings of 25% LPV and 6.3% RTV. A slow release rate of LPV was observed at about 20% on day 5, followed by a sustained release beyond 14 days. RTV released faster than LPV in the first 5 days and slower than LPV thereafter. LPV trough concentration remained above 160 ng/mL and RTV trough concentration was above 50 ng/mL after 6 days with one subcutaneous injection. Overall, the ISNP-based LPV/RTV injection showed sustained release profiles in both in vitro and in vivo studies.

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