Size-Dependent Drug Loading, Gene Complexation, Cell Uptake, and Transfection of a Novel Dendron-Lipid Nanoparticle for Drug/Gene Co-delivery

2021 ◽  
Author(s):  
Ashita Nair ◽  
Jiyoon Bu ◽  
Jason Bugno ◽  
Piper A. Rawding ◽  
Luke J. Kubiatowicz ◽  
...  
Keyword(s):  
Drug Loading ◽  
Cell Uptake ◽  
Size Dependent ◽  
Lipid Nanoparticle

Formulation Development of Tamoxifen Loaded Lipid Nanoparticle by Taguchi (L12 (2 11)) Orthogonal Array Design

2020 ◽  
Vol 16 ◽  
Author(s):  
Poovi Ganesan ◽  
N Damodharan
Keyword(s):  
Orthogonal Array ◽  
Drug Loading ◽  
Optimization Technique ◽  
Pharmaceutical Products ◽  
Water Soluble ◽  
Nanostructured Lipid Carrier ◽  
Orthogonal Array Design ◽  
Formulation Development ◽  
Array Design ◽  
Lipid Nanoparticle

Background: A better understanding of the biopharmaceutical and physicochemical properties of drugs and the pharmaco-technical factors would be of great help for developing pharmaceutical products. But, it is extremely difficult to study the effect of each variable and interaction among them through the conventional approach Objective: To screen the most influential factors affecting the particle size (PS) of lipid nanoparticle (LNPs) (solid lipid nanoparticle (SLN) and nanostructured lipid carrier (NLC)) for poorly water-soluble BCS class-II drug like tamoxifen (TMX) to improve its oral bioavailability and to reduce its toxicity to tolerable limits using Taguchi (L12 (2 11)) orthogonal array design by applying computer optimization technique. Results: The size of all LNPs formulations prepared as per the experimental design varied between 172 nm and 3880 μm, polydispersity index between 0.033 and 1.00, encapsulation efficiency between 70.8% and 75.7%, and drug loading between 5.84% and 9.68%. The study showed spherical and non-spherical as well as aggregated and non-aggregated LNPs. Besides, it showed no interaction and amorphous form of the drug in LNPs formulation. The Blank NLCs exhibited no cytotoxicity on MCF-7 cells as compared to TMX solution, SLNs (F5) and NLCs (F12) suggests that the cause of cell death is primarily from the effect of TMX present in NLCs. Conclusions: The screening study clearly showed the importance of different individual factors significant effect for the LNPs formulation development and its overall performance in an in-vitro study with minimum experimentation thus saving considerable time, efforts, and resources for further in-depth study.

Size-Dependent Cell Uptake of Protein-Coated Graphene Oxide Nanosheets

2012 ◽  
Vol 4 (4) ◽  
pp. 2259-2266 ◽  
Author(s):  
Qingxin Mu ◽  
Gaoxing Su ◽  
Liwen Li ◽  
Ben O. Gilbertson ◽  
Lam H. Yu ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Cell Uptake ◽  
Graphene Oxide Nanosheets ◽  
Size Dependent ◽  
Dependent Cell

Elimination of Quantum Dots Cell Uptake

2009 ◽  
Vol 1236 ◽  
Author(s):  
Hengyi Xu ◽  
Zoraida Pascual Aguilar ◽  
Ben Jones ◽  
Hua Wei ◽  
Andrew Wang
Keyword(s):  
Cellular Uptake ◽  
Targeted Delivery ◽  
New Technology ◽  
Binding Activity ◽  
Cell Uptake ◽  
Biological Research ◽  
Size Dependent ◽  
Small Bandwidth ◽  
Specific Uptake ◽  
Surface Modified

AbstractThe nanotechnology is undergoing enormous attention in the areas of biological research for clinical, environmental, and life sciences applications. One of the products from this new technology that attracts researcher’s attentions is the semiconductor quantum dot (QDs) nanoparticles, QDs possess incomparable advantages such as unique size-dependent physical properties, broad absorption spectrum, precise small bandwidth emission wavelength, as well as enhanced chemical and photochemical stability. The QDs can be modified for a controlled and enhanced endocytosis, enhanced cooperative binding activity, and easy introduction of multi-functionalities for medical applications such as targeted delivery and imaging. It can be used for complex studies that play very important roles in the modern biomedical researches. However, when performing the cell related assays, the non-specific cellular uptake of QDs is a major concern because they can lead to false positives or false results. In our study, we used different surface modified QDs treated with different blocking buffers to eliminate cellular uptake. The preliminary results showed that the cellular uptake of QDs can be eliminated by surface modification of the QD materials and by performing the assays in the presence of blocking buffers. As a result of the elimination of non-specific uptake of QDs the sensitivity and specificity of detection increased significantly.

scholarly journals Formulation of Solid Lipid Nanoparticles of Cilnidipine for the Treatment of Hypertension

2019 ◽  
Vol 9 (3) ◽  
pp. 212-221 ◽  
Author(s):  
Aparna Bhalerao ◽  
Pankaj Prakash Chaudhari
Keyword(s):  
Particle Size ◽  
Solid Lipid Nanoparticles ◽  
Encapsulation Efficiency ◽  
Drug Loading ◽  
Lipid Nanoparticles ◽  
Water Soluble ◽  
Solid Lipid Nanoparticle ◽  
Solid Lipid ◽  
Lipid Nanoparticle

Cilinidipine is a fourth generation N and L-type calcium channel antagonists used alone or in combination with another drug to treat hypertension. Cilnidipine is poorly water -soluble, BCS class II drug with 6 to 30 percent oral bioavailability due to first pass metabolism. So to protect the drug from degradation and improve its dissolution, solid lipid nanoparticles were prepared. Glyceryl monostearate was selected as lipid while span 20: tween 20 were selected as surfactant blends. The formulations were evaluated for various parameters, as percent transmittance, drug content, percent encapsulation efficiency; percent drug loading, In vitro drug release and particle size. Optimized formulation was lyophilized using lactose as a cryo-protectant. The lyophilized formulation was evaluated for micromeritic properties, particle size and in vitro dissolution. It was further evaluated for DSC, XRD, and SEM. Percent encapsulation efficiency and percent drug loading of optimized formulation (F3) were 78.66percent and 9.44percent respectively. The particle size of F3 formulation without drug was 204 nm and with the drug was 214 nm. The particle size of the reconstituted SLN was 219 nm. In DSC study, no obvious peaks for cilnidipine were found in the SLN of cilnidipine indicated that the cilnidipine must be present in a molecularly dissolved state in SLN. In X-ray diffractometry absence of peaks representing crystals of cilnidipine in SLN indicated that the drug was in an amorphous or disordered crystalline phase in the lipid matrix. Thus, solid lipid nanoparticle formulation is a promising way to enhance the dissolution rate of cilnidipine. Keywords: Cilnidipine, Solid Lipid Nanoparticle, Hypertension

scholarly journals Targeting study of HepG2 hepatoma cells in vitro by drug-loaded pectin-based nanoparticles

2019 ◽  
Author(s):  
Anil Shumroni ◽  
David Gupta
Keyword(s):  
Mtt Assay ◽  
Hepg2 Cells ◽  
Hepatoma Cell ◽  
Drug Loading ◽  
A549 Cells ◽  
Cell Uptake ◽  
Dependent Manner ◽  
Human Hepatoma Cell ◽  
Significant Difference ◽  
Dose Dependent

AbstractThe biodegradable and biodegradable natural polysaccharide has always been used as a drug delivery system, and has the following advantages: It can prolong the biological half life of the drug and reduce the side effects of the drug. This experiment aimed to prepare a 5-fluorouracil (5-FU) nanoparticle (P-5-FU) drug-loading system based on pectin, and explored a large number of pectin-based nano drug-loading systems. The galactose residue is a natural target that targets human hepatoma cell HepG2. MTT assay was used to determine the proliferation inhibition effect of drug-loaded pectin-based nanoparticles on HepG2 and A549 cells. MTT assay showed that P-5-FU inhibited the proliferation of HepG2 cells in a dose-dependent manner, and the effect was stronger than 5-FU. P-5-FU also inhibited the proliferation of A549 cells in a dose-dependent manner, but there was no significant difference compared with 5-FU. High performance liquid chromatography (HPLC) on two kinds of cells loaded with drug-loaded nanoparticles the uptake and targeting were measured. The results of cell uptake showed that the uptake of P-5-FU by HepG2 cells was significantly higher than that of 5-FU, but there was no significant difference in the uptake of P-5-FU and 5-FU by A549 cells. There was no significant difference in the uptake of P-5-FU and 5-FU between the two cells after the galactose-saturated ASGPR binding site. The results indicate that pectin-based nano drug-loaded particles can specifically target highly expressed cells.

scholarly journals Size-Dependent Biological Effects of Quercetin Nanocrystals

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1438 ◽  
Author(s):  
Qian Liu ◽  
Xi Yang ◽  
Jianxu Sun ◽  
Fanglin Yu ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Particle Size ◽  
Biological Effects ◽  
Drug Loading ◽  
A549 Cells ◽  
Migration And Invasion ◽  
Dissolution Behavior ◽  
Dependent Manner ◽  
Wet Milling ◽  
Antitumor Effects ◽  
Size Dependent

Quercetin (QE) is an attractive natural compound for cancer prevention due to its beneficial anti-oxidative and anti-proliferative effects. However, QE is poorly soluble in water and slightly soluble in oil, which results in its low oral bioavailability and limits its application in the clinic. The aim of this study was to prepare QE nanocrystals (QE-NCs) with improved solubility and high drug loading, furthermore, the size-dependent anti-cancer effects of QE-NCs were studied. We prepared QE-NCs with three different particle sizes by wet milling, then, cell proliferation, migration and invasion were studied in A549 cells. The QE-NCs had antitumor effects in a dose- and size-dependent manner. Compared with the large particles, the small particles had a strong inhibitory impact on cell biological effects (p < 0.05 or p < 0.01). Moreover, Western blot assay indicated that QE-NCs may inhibit the migration and invasion of A549 cells by inhibiting the STAT3 signaling pathway, and the particle size may have an effect on this process. In this study, it was proven that NCs could dramatically enhance the anticancer efficacy of QE at the cellular level. In addition, particle size had a considerable influence on the dissolution behavior and antitumor effects of NCs.

scholarly journals Enabling online determination of the size-dependent RNA content of lipid nanoparticle-based RNA formulations

2021 ◽  
pp. 123015
Author(s):  
Xiujuan Jia ◽  
Yong Liu Conceptulization ◽  
Angela M. Wagner ◽  
Michelle Chen ◽  
Yuejie Zhao ◽  
...  
Keyword(s):  
Size Dependent ◽  
Rna Content ◽  
Lipid Nanoparticle

scholarly journals Enhanced In Vitro Magnetic Cell Targeting of Doxorubicin-Loaded Magnetic Liposomes for Localized Cancer Therapy

Nanomaterials ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2104
Author(s):  
Eugenio Redolfi Riva ◽  
Edoardo Sinibaldi ◽  
Agostina Francesca Grillone ◽  
Serena Del Turco ◽  
Alessio Mondini ◽  
...  
Keyword(s):  
Colloidal Stability ◽  
Clinical Investigation ◽  
Drug Loading ◽  
Superparamagnetic Nanoparticles ◽  
Cell Uptake ◽  
Magnetic Drug Targeting ◽  
Magnetic Targeting ◽  
Liver Malignancies ◽  
In Vitro Investigation

The lack of efficient targeting strategies poses significant limitations on the effectiveness of chemotherapeutic treatments. This issue also affects drug-loaded nanocarriers, reducing nanoparticles cancer cell uptake. We report on the fabrication and in vitro characterization of doxorubicin-loaded magnetic liposomes for localized treatment of liver malignancies. Colloidal stability, superparamagnetic behavior and efficient drug loading of our formulation were demonstrated. The application of an external magnetic field guaranteed enhanced nanocarriers cell uptake under cell medium flow in correspondence of a specific area, as we reported through in vitro investigation. A numerical model was used to validate experimental data of magnetic targeting, proving the possibility of accurately describing the targeting strategy and predict liposomes accumulation under different environmental conditions. Finally, in vitro studies on HepG2 cancer cells confirmed the cytotoxicity of drug-loaded magnetic liposomes, with cell viability reduction of about 50% and 80% after 24 h and 72 h of incubation, respectively. Conversely, plain nanocarriers showed no anti-proliferative effects, confirming the formulation safety. Overall, these results demonstrated significant targeting efficiency and anticancer activity of our nanocarriers and superparamagnetic nanoparticles entrapment could envision the theranostic potential of the formulation. The proposed magnetic targeting study could represent a valid tool for pre-clinical investigation regarding the effectiveness of magnetic drug targeting.

scholarly journals Time evolution of PEG-shedding and serum protein coronation determines the cell uptake kinetics and delivery of lipid nanoparticle formulated mRNA

2021 ◽  
Author(s):  
Audrey Gallud ◽  
Michael J Munson ◽  
Kai Liu ◽  
Alexander Idstrom ◽  
Hanna MG Barriga ◽  
...  
Keyword(s):  
Serum Proteins ◽  
Short Pulse ◽  
High Surface ◽  
Protein Corona ◽  
Cell Uptake ◽  
Lipid Nanoparticle ◽  
Nanoparticle Imaging ◽  
Early Endosomes ◽  
Corona Formation ◽  
Model Protein

Development of efficient lipid nanoparticle (LNP) vectors remains a major challenge towards broad clinical translation of RNA therapeutics. New lipids will be required, but also better understanding LNP interactions with the biological environment. Herein, we model protein corona formation on PEG-ylated DLin-MC3-DMA LNPs and identify time-dependent maturation steps that critically unlock their cellular uptake and mRNA delivery. Uptake requires active serum proteins and precedes after a significant (~2 hours) lag-time, which we show can be eliminated by pre-incubating LNPs for 3-4 hours in serum-containing media. This indicates an important role of protein corona maturation for the pharmacokinetic effects of these LNPs. We show, using single-nanoparticle imaging, NMR diffusometry, SANS, and proteomics, that the LNPs, upon serum exposure, undergo rapid PEG-shedding (~30 minutes), followed by a slower rearrangement of the adsorbed protein layer. The PEG-shedding coincides in time with high surface abundance of Apolipoprotein A-II, whereas the LNPs preferentially bind Apolipoprotein E when their maximum uptake-competent state is reached. Finally, we show that pre-incubation of the LNPs enables rapid uptake and allows pulse-chase video-microscopy colocalization experiments with sufficiently short pulse durations to gain improved mechanistic understanding of how intracellular trafficking events determine delivery efficacy, emphasizing early endosomes as important delivery-mediating compartments.

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