scholarly journals LipiSensors: Exploiting Lipid Nanoemulsions to Fabricate Ionophore-Based Nanosensors

Biosensors ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. 120 ◽  
Author(s):  
Alexandra L. Dailey ◽  
Meredith D. Greer ◽  
Tyler Z. Sodia ◽  
Megan P. Jewell ◽  
Tabitha A. Kalin ◽  
...  

Ionophore-based nanosensors (IBNS) are tools that enable quantification of analytes in complex chemical and biological systems. IBNS methodology is adopted from that of bulk optodes where an ion exchange event is converted to a change in optical output. While valuable, an important aspect for application is the ability to intentionally tune their size with simple approaches, and ensure that they contain compounds safe for application. Lipidots are a platform of size tunable lipid nanoemulsions with a hydrophobic lipid core typically used for imaging and drug delivery. Here, we present LipiSensors as size tunable IBNS by exploiting the Lipidot model as a hydrophobic structural support for the sensing moieties that are traditionally encased in plasticized PVC nanoparticles. The LipiSensors we demonstrate here are sensitive and selective for calcium, reversible, and have a lifetime of approximately one week. By changing the calcium sensing components inside the hydrophobic core of the LipiSensors to those sensitive for oxygen, they are also able to be used as ratiometric O2 sensitive nanosensors via a quenching-based mechanism. LipiSensors provide a versatile, general platform nanosensing with the ability to directly tune the size of the sensors while including biocompatible materials as the structural support by merging sensing approaches with the Lipidot platform.

2021 ◽  
Vol 50 (12) ◽  
pp. 3693-3703
Author(s):  
Wai Mun Chong ◽  
Erazuliana Abd Kadir

Glycol chitosan (GC) is the chitosan derivative that is capable of forming amphiphilic nanoparticles upon structure modifications at the reactive functional amine group on the polymer sugar backbone. Owing to the hydrophilic feature of GC and hydrophobic moieties that can be added to the GC structure, modifiable nanosystems were constructed to entrap poorly soluble drugs, mostly chemotherapeutic agents and several anti-inflammatory, anaesthetic, immunosuppressant, and antifungal drugs for more efficient delivery of the payload to the target site and improving the intended therapeutic effects. This review highlights the various hydrophobic molecules used in the chemical modification of GC to create amphiphilic nanoparticles for hydrophobic drug delivery, along with the summary of their physicochemical criteria and successful therapeutic enhancement achieved with the application of the drug-loaded amphiphiles. The biodegradable, GC-based nanoparticles particularly having the inner hydrophobic core and outer hydrophilic shell are an efficient system for drug entrapment, protection and targeting to improve the bioavailability and safety of the drug, in particular for cancer treatment purposes. The significant drug delivery enhancements achieved by these various hydrophobically-modified GC nanoparticles may provide the insights for their further use in nanomedicine.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1413
Author(s):  
Anne Yagolovich ◽  
Andrey Kuskov ◽  
Pavel Kulikov ◽  
Leily Kurbanova ◽  
Dmitry Bagrov ◽  
...  

Nanoparticles based on the biocompatible amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) derivatives are promising for drug delivery. Amph-PVPs self-aggregate in aqueous solutions with the formation of micellar nanoscaled structures. Amph-PVP nanoparticles are able to immobilize therapeutic molecules under mild conditions. As is well known, many efforts have been made to exploit the DR5-dependent apoptosis induction for cancer treatment. The aim of the study was to fabricate Amph-PVP-based nanoparticles covalently conjugated with antitumor DR5-specific TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) variant DR5-B and to evaluate their in vitro cytotoxicity in 3D tumor spheroids. The Amph-PVP nanoparticles were obtained from a 1:1 mixture of unmodified and maleimide-modified polymeric chains, while DR5-B protein was modified by cysteine residue at the N-end for covalent conjugation with Amph-PVP. The nanoparticles were found to enhance cytotoxicity effects compared to those of free DR5-B in both 2D (monolayer culture) and 3D (tumor spheroids) in vitro models. The cytotoxicity of the nanoparticles was investigated in human cell lines, namely breast adenocarcinoma MCF-7 and colorectal carcinomas HCT116 and HT29. Notably, DR5-B conjugation with Amph-PVP nanoparticles sensitized resistant multicellular tumor spheroids from MCF-7 and HT29 cells. Taking into account the nanoparticles loading ability with a wide range of low-molecular-weight antitumor chemotherapeutics into hydrophobic core and feasibility of conjugation with hydrophilic therapeutic molecules by click chemistry, we suggest further development to obtain a versatile system for targeted drug delivery into tumor cells.


2020 ◽  
pp. 1-4
Author(s):  
Ignác Capek ◽  
Ignác Capek

Need for materials with high biocompatible properties have led to the development of prodrug-decorated nanoparticles. The structure of present nanostructures consists of the hydrophobic core and hydrophilic shell. The shell acts as an external envelop which enhances the colloidal stability of dispersion which protects the prodrug of the nanoparticles from photo- and thermal-initiated degradation. The composite nanoparticles coated by organic shells with functional groups were considered to govern the covalent immobilization of therapeutics/biomolecules. The nanoparticles with unique physiochemical properties may be useful as biosensors in living whole cells. The enhanced cellular drug delivery to cancer cell lines via nanoconjugates revealed that smart nanoparticles are an effective tool for transporting and delivering drugs.


2012 ◽  
Vol 8 (5) ◽  
pp. 1891-1900 ◽  
Author(s):  
Danya M. Lavin ◽  
Robert M. Stefani ◽  
Linda Zhang ◽  
Stacia Furtado ◽  
Richard A. Hopkins ◽  
...  

2022 ◽  
pp. 517-537
Author(s):  
Dr.Sumira Malik ◽  
Shristi Kishore ◽  
Shradha A. Kumari ◽  
Anjali Kumari

The area of healthcare needs new innovative methods and tools for improvisation and to impart better efficiencies. Nanoemulsions are pharmaceutical formulations containing nanometre-sized particles used for controlled and systemic delivery of bioactive pharmaceuticals. Various advantageous properties of nanoemulsions such as the presence of hydrophobic core region, higher stability, and smaller size have made them useful to a large extent in the biomedical field. They have been employed in transdermal drug delivery, intranasal drug delivery, pulmonary drug delivery, parenteral drug delivery, and improvised delivery of hydrophobic drugs. This chapter aims to discuss various applications of nanoemulsions in healthcare including cosmetics, antimicrobials, vaccine delivery, targeted drug delivery, gene delivery, cancer therapy, and many more in detail.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fan Li ◽  
Yan Liang ◽  
Miaochen Wang ◽  
Xing Xu ◽  
Fen Zhao ◽  
...  

AbstractSynergistic chemo-photodynamic therapy has garnered attention in the field of cancer treatment. Here, a pH cascade-responsive micellar nanoplatform with nucleus-targeted ability, for effective synergistic chemo-photodynamic cancer treatment, was fabricated. In this micellar nanoplatform, 5-(4-carboxyphenyl)-10,15,20-triphenylporphyrin (Por), a photodynamic therapy (PDT) agent was utilized for carrying the novel anticancer drug GNA002 to construct a hydrophobic core, and cyclic RGD peptide (cRGD)-modified polyethylene glycol (PEG) (cRGD-PEG) connected the cell-penetrating peptide hexaarginine (R6) through a pH-responsive hydrazone bond (cRGD-PEG-N = CH-R6) to serve as a hydrophilic shell for increasing blood circulation time. After passively accumulating in tumor sites, the self-assembled GNA002-loaded nanoparticles were actively internalized into cancer cells via the cRGD ligands. Once phagocytosed by lysosomes, the acidity-triggered detachment of the cRGD-PEG shell led to the formation of R6-coated secondary nanoparticles and subsequent R6-mediated nucleus-targeted drug delivery. Combined with GNA002-induced nucleus-specific chemotherapy, reactive oxygen species produced by Por under 532-nm laser irradiation achieved a potent synergistic chemo-photodynamic cancer treatment. Moreover, our in vitro and in vivo anticancer investigations revealed high cancer-suppression efficacy of this ideal multifunctional nanoplatform, indicating that it could be a promising candidate for synergistic anticancer therapy.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 258 ◽  
Author(s):  
Di Xiong ◽  
Liyang Wen ◽  
Shiyuan Peng ◽  
Jianchang Xu ◽  
Lijuan Zhang

Good stability and controlled drug release are important properties of polymeric micelles for drug delivery. A good candidate for drug delivery must have outstanding stability in a normal physiological environment, followed with low drug leakage and side effects. Moreover, the chemotherapeutic drug in the micellar core should also be quickly and “on-demand” released in the intracellular microenvironment at the tumor site, which is in favor of overcoming multidrug resistance (MDR) effects of tumor cells. In this work, a mixed micelle was prepared by the simple mix of two amphiphilic copolymers, namely PCL-SS-P(PEGMA-co-MAEBA) and PCL-SS-PDMAEMA, in aqueous solution. In the mixed micelle’s core–shell structure, PCL blocks were used as the hydrophobic core, while the micellar hydrophilic shell consisted of two blocks, namely P(PEGMA-co-MAEBA) and PDMAEMA. In the micellar shell, PEGMA provided hydrophilicity and stability, while MAEBA introduced the aldehyde sites for reversible crosslinking. Meanwhile, the PDMAEMA blocks were also introduced in the micellar shell for pH-responding protonation and swelling of the micelle. The disulfide bonds between the hydrophobic core and hydrophilic shell had redox sensitive properties. Reversible cross-linked micelles (RCLMs) were obtained by crosslinking the micellar shell with an imine structure. RCLMs showed good stability and excellent ability against extensive dilution by aqueous solution. In addition, the stability in different conditions with various pH values and glutathione (GSH) concentrations was studied. Then, the anticancer drug doxorubicin (DOX) was selected as the model drug to evaluate drug entrapment and release capacity of mixed micelles. The in vitro release profiles indicated that this RCLM had controlled drug release. In the simulated normal physiological environment (pH 7.4), the drug release of the RCLMs was restrained obviously, and the cumulative drug release content was only 25.7 during 72 h. When it came to acidic conditions (pH 5.0), de-crosslinking of the micelles occurred, as well as protonation of PDMAEMA blocks and micellar swelling at the same time, which enhanced the drug release to a large extent (81.4%, 72 h). Moreover, the drug release content was promoted further in the presence of the reductant GSH. In the condition of pH 5.0 with 10 mM GSH, disulfide bonds broke-up between the micelle core and shell, followed by shedding of the shell from the inner core. Then, the micellar disassembly (degradation) happened based on the de-crosslinking and swelling, and the drug release was as high as 95.3%. The MTT assay indicated that the CLSMs showed low cytotoxicity and good biocompatibility against the HepG2 cells. In contrast, the DOX-loaded CLSMs could efficiently restrain the proliferation of tumor cells, and the cell viability after 48 h incubation was just 13.2%, which was close to that of free DOX. This reversible cross-linked mixed micelle with pH/redox responsive behaviors is a potential nanocarrier for chemotherapy.


2020 ◽  
Vol 11 (1) ◽  
pp. 176-184
Author(s):  
Pooja Mallya ◽  
Gowda D V ◽  
Mahendran B ◽  
Bhavya M V ◽  
Vikas Jain

Targeting of the drug directly to the cells, tissues, or organs with no impact on healthy cells is a challenge. In the current era, it's been made possible by therapeutic interventions. The novel drug delivery systems such as nano particulates, liposomes, aquasomes, phytosomes, dendrimers, nano sponges, nano micelles are developed. Nano micelles are developed for efficient targeting and are currently in trend as therapeutic carriers of water-insoluble drugs. Micelles are self-assembling Nano-sized colloidal particles with a hydrophobic core and hydrophilic shell. Among the micelle-forming compounds, amphiphilic copolymers, i.e., polymers consisting of hydrophobic block and hydrophilic block, are gaining increasing attention. Polymeric micelles possess high stability both in vitro and in vivo with good biocompatibility. Nano micelles are used widely because of the smaller size range of 10 to 100nm, with greater drug loading capacity. Advantages over other dosage forms include solubilization of poorly soluble drugs, sustained release, protection of drugs from degradation and metabolism. The property discussed includes CMC, size, and aggregation number, and stability. CMC is the minimum polymer concentration required for micelle formation. Aggregation number (Nₐ) is the number of polymeric chains required to form micelles, and it ranges between tens to hundreds. Thermodynamic stability is based on size, the optical clarity of solution, viscosity, and surface tension. Kinetic stability accounts for micellar integrity. This review will discuss some recent trends in using micelles as pharmaceutical carriers such as to deliver drugs in conditions such as TB, cancer, ocular complications, etc.


2017 ◽  
Vol 5 (23) ◽  
pp. 4443-4454 ◽  
Author(s):  
Xufeng Zhou ◽  
Cong Chang ◽  
Yang Zhou ◽  
Lu Sun ◽  
Hua Xiang ◽  
...  

Two types of thermo-sensitive DHBCs-based micelle prodrugs with drug tethered to the hydrophilic shell or encapsulated with the hydrophobic core was fabricated, and compared further for their drug delivery efficacy.


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