Potential Applications of Nanoparticles and Cell Derived Nanovesicles
1Shubham Kumar, 2Shambhavi, Manoj Kumar Singh and Chirag Choudhary
1Ph.D. Scholar, Veterinary Pharmacology and Toxicology, ICAR-IVRI, Izatnagar, Bareilly, Uttar Pradesh
2Assistant Technical Manager, Rossari Biotech Limited, Chandigarh, Punjab
3Assistant Professor, Department of Livestock Production Management, SVPUAT, Meerut, Uttar Pradesh
4Ph.D. Scholar, Division of Animal Genetics and Breeding, ICAR-IVRI, Izatnagar, Bareilly, Uttar Pradesh
INTRODUCTION
Nanoparticles are nanosized colloidal structures composed of synthetic or semisynthetic polymers whose size range is about 1 – 100 nm in diameter. The drug is either dissolved, entrapped, encapsulated, or attached to nanoparticle matrix.The first reported nanoparticles were based on non- biodegradable polymeric system that is polyacrylamide, polymethyl methacrylate, polysterene etc. by Birrenbach and Speiser, 1976.These nanoparticles are increasingly used in different applications, including drug carrier systems and to pass organ barriers such as the blood-brain barrier. Because of their unique properties Nanocrystals and other nanoparticles have been receiving a lot of attention for potential use in Therapeutics, Bioengineering and drug discovery.
TYPES OF NANOPARTICLES
MICELLES
Micelles are nanostructures made of amphiphilic molecules, like polymers or lipids. When exposed to aqueous environments, they hide their hydrophobic groups inside the structure and expose the hydrophilic groups. On the other hand, when in lipid-rich environments, their structure may organizes in a reverse way.
MICELLES 
LIPOSOMES
LIPOSOMES
Liposomes are concentric bilayered vesicles in which an aqueous volume is entirely enclosed by a membranous lipid bilayer mainly composed of natural or synthetic phospholipids Liposomes have been used successfully in the field of biology, biocemistry and medicine. Main advantages, they are completely biodegradable, compatible, non-toxic and non-immunogenic.
DENDRIMER
Dendrimers, a unique class of polymers, highly branched macromolecules whose size and shape can be precisely controlled. Drug molecules can be incorporated into dendrimers via either complexation or encapsulation. Dendrimers are being investigated for both drug and gene delivery, as carriers for penicillin, and for use in anticancer therapy.
HYBRID NANOPARTICLES
An intermediate type of NPs is the CSPL hybrid NPs. In its structure a biodegradable hydrophobic polymeric core and a lipidic outer monolayer are present. CSPL hybrid NPs bring together complementary characteristics of both structures, namely higher stability, enhanced drug encapsulation yield and superior in vivo cellular delivery efficacy.
COMPACT POLYMERIC NPs
Compact polymeric NPs are nanostructures made entirely of natural or synthetic polymers. They are usually more stable than liposomes allowing sustained localized drug delivery for weeks, with reduced drug leakage.
CARBON STRUCTURES
NPs can also be simply made of carbon molecules with various highly symmetric and stable forms, called fullerenes (allotrope of carbon). C60 the most well-known fullerene, is a rigid icosahedron with 60 carbon atoms. Their unique optic, electric and magnetic properties (such as superconductivity), rendering them important devices in medical diagnosis and imaging.
QUANTUM DOTS
Quantum dots used in imaging, detection and targeting the cells are luminescent semiconductor crystals. Quantum dots present a broad absorption range and narrow emission spectra. quantum dots present high photostability, being remarkably resistant to photobleaching. The use of quantum dots is based on their unique chemical and physical properties, achieved due to their size and highly compact structure.
SILICONS
The most commonly investigated silicon-based materials for drug delivery are porous silicon and silica, or silicon dioxide. Examples of therapies with silicon-based delivery systems include porous silicon embedded with platinum as an antitumor agent. CPS designed as an artificial growth factor. Silicon nanopores for antibody delivery. Porous silica nanoparticles containing antibiotics, enzymes, and DNA.
APPLICATIONS OF NPs
TARGETED DRUG DELIVERY
A key area in drug delivery is the accurately targeting of the drug to cells or tissue of choice. Nanoparticles can be used in targeted drug delivery at the site of disease to improve the uptake of poorly soluble drugs the targeting of drugs to a specific site, and drug bioavailability. Several anti-cancer drugs including paclitaxel, Dox,5fU and dexamethasone have been successfully formulated using nanomaterials. PLGA and PLA based nanoparticles have been formulated to encapsulate dexamethasone. Being a glucocorticoid, dexamethasone is a chemotherapeutic agent that has anti-proliferative and anti-inflammatory effects.
Gold NPs (Detect cancer)
Gold nanoparticles used as ultrasensitive fluorescent probes to detect cancer biomarkers in human blood. Gold nanoparticles are promising probes for biomedical applications because they can be easily prepared and, unlike other fluorescent probes such as quantum dots or organic dyes, don’t burn out after long exposure to light.
Stem cell Therapy and Imaging
Nanoparticles may prove effective tools for improving stem cell therapy. Chemical engineers have successfully used nanoparticles to enhance stem cells’ ability to stimulate regeneration of damaged vascular tissue and reduce muscle degeneration in mice. Nanoparticles can be designed to enhance fluorescent imaging or to enhance images from PET or ultrasound. Nanoparticles and nanofibres play an important part in the design and manufacture of novel scaffold structures for tissue and bone repair. The nanomaterials used in such scaffolds are biocompatible. For example, nanoparticles of CHA, a natural component of bone, used in combination with collagen or collagen substitutes could be used in future tissue-repair therapies.
Other applications
- Nanoparticles can act as controlled release system depending on their polymeric composition.
- less amount of dose is required.
- Reduce side effects & reduce drug toxicity.
- Can be administered by various routes – oral, nasal, intra occular etc.
- Particle size and surface characteristics of nanoparticles can be easily manipulated to achieve both passive and active drug targeting after parenteral administration.
- Nanoparticles aid in efficient drug delivery to improve aqueous solubility of poorly soluble drugs.
- Nanoparticles overcome the resistance offered by the physiological barriers in the body.
CELL MEMBRANE DERIVED NANOVESICLES
Unlike synthetic lipid or polymeric nanoparticles, cell membrane-derived vesicles have a unique multicomponent feature, comprising lipids, proteins, and carbohydrates. Cell membrane-derived vesicles can carry therapeutic agents within their interior or can coat the surfaces of drug-loaded core nanoparticles. Cell membranes typically come from single cell sources, including red blood cells, platelets, immune cells, stem cells, and cancer cells.
PREPARATIONS OF CMDVs
- Cell membrane-derived vesicles are prepared through a multistep process that includes digestion of parent cells, purification of cell membranes, and formation of vesicles.
- First, the parental cells are broken down by lysing with a hypotonic buffer.
- Second, the mixture of cell membranes and other cellular components, such as cell nucleus and cytoplasmic organelles, are separated by centrifugation.
- Third the collected cell membrane is physically broken (by homogenization, sonication, extrusion, and nitrogen cavitation) to yield cell membrane nanovesicles of the size of interest.
- Functions of CMDVs can be modified using two basic strategies: pre-modification and post modification.
- With pre-modification changes made before disruption of parent cells, and post-modification corresponding to introduction of new components into membranes after isolation.
- Post modification of CMDVs were modified with various materials to modulate their chemical and biological behaviors.
(A) lipid compositions of membranes were modified to increase the stability of vesicles.
(B) Enzymes or other proteins were grafted onto the surface of cell membrane vesicles to provide functionality.
(C) Nucleic acids,such as aptamers, were conjugated to cell membrane vesicles for targeted delivery.
(D) Synthetic polymers (such as PEG) were grafted into cell membrane vesicles to prolong their circulation time in blood.
APPLICATIONS OF CMDVs
RBCs membrane derived vesicles- RBC membranes have received considerable attention as a nanoparticle-coating biomaterial. Dox loaded MPPB nanoparticles have been coated with RBC membranes for photo-chemotherapy applications. Plain MPPB nanoparticles suffer from physical instability, short half-life, and nonspecific uptake by macrophages. The RBC membrane coating improves these pharmacokinetic properties, increasing blood circulation time and decreasing non-specific uptake; it also provides synergistic anticancer effects through combined chemotherapeutic and photo therapeutic actions.
PLATELETS MEMBRANE DERIVED NVS
Researchers in the drug-delivery field have developed an interest in platelets because of their ability to target specific sites and evade the immune system. Platelet membranes were used to coat PLGA nanoparticles with imaging agents. For diagnostic imaging, a fluorescent dye was loaded into PLGA nanoparticles, with concurrent incorporation of lipid-chelated gadolinium into the lipid bilayer of the platelet membrane. The resulting membrane-coated nanoparticles provided magnetic resonance imaging capability that was localized to regions of arteries that are prone to plaque formation.
STEM CELL DERIVED VESICLES
Stem cell membranes have been used to coat drug-loaded nanoparticles. PLGA nanoparticles have been coated with cardiac stem cell membranes for use in tissue-repair applications. In this application, direct intramuscular injection of cardiac stem cell membrane-coated nanoparticles carrying stem cell-secreted proteins was found to alleviate symptoms in a mouse model of myocardial infarction
CANCER CELL DERIVED VESICLES
Cancer cell membrane-coated nanoparticles have been studied for a variety of cancer therapy applications as cancer cell membrane’s have ability to penetrate the blood‒brain barrier. Coated polycaprolactone/F68 nanoparticles with brain metastatic tumor cell membranes and loaded the resulting nanoparticles with indocyanine green, used as an imaging and photothermal agent. Intravenously injected nanoparticles were shown to distribute to the brain in glioma cell-bearing mice. Cancer cell membrane-coated nanoparticles showed greater accumulation in the brain compared with uncoated nanoparticles.
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