With the advancement in science and technology, innovative and more efficient techniques have been developed to aid in disease diagnosis and treatment. Nanotechnology has been largely implicated to devise new medical tools for these purposes. One such application of nanotechnology is “Nanogel”.
Nanogels or hydrogels are three-dimensional, highly cross-linked, polymeric, spherical particles or fabrications that range in size from 20 to 200 nm https://www.ncbi.nlm.nih.gov/pubmed/?term=19592087%5Buid%5D. They are hydrophilic in nature with an enormous tendency to imbibe water. High water content enables nanogels to act like body fluid in drug delivery system for the transport of drugs or biomolecules to the target site https://www.mdpi.com/1996-1944/3/2/1420.
Nanogels are composed of either natural or synthetic polymers, such as; chitosan, dextran, dextrin, methyl cellulose, ethyl cellulose or pullulan etcetera cross-linked with a number of ligands which are responsible for targeted drug release in response to a specific chemical or biological stimulus. Apart from use in drug delivery, nanogels can serve for various other purposes including their use in scaffold formation, nanomedicines, immunosuppressants, biosensors, artificial muscles and anticancer therapies.
Nanogels exhibit marvelous physical and chemical properties, for example; softness, amphiphilicity, non-toxicity, low viscosity, thermodynamic and colloidal stability, swelling/deswelling in presence of aqueous medium, large drug loading capacity, inertness in systemic circulation and body fluids, biodegradability and biocompatibility. These characteristics contribute to their use in medical science.
Types of Nanogels
Based on Response Towards Specific Stimuli
- Stimulus responsive nanogels: They are sensitive to changes in environmental conditions i.e. temperature, pH, magnetic field, and ionic strength. Any change in these factors act as a stimulus and eventually leads to swelling/deswelling of nanogel resulting in drug release http://www.japsonline.com/admin/php/uploads/1060_pdf.pdf.
- Non-responsive nanogels: Such nanogels are not stimulated by changes environmental factors. Instead, their functioning is triggered by presence or absence of water http://www.japsonline.com/admin/php/uploads/1060_pdf.pdf.
Based on Type of Cross-Linking
Physically cross-linked nanogels: Pseudo gels or physically cross-linked nanogels are composed of polymeric substances bonded by weak chemical linkages, such as; van der Waals forces, hydrogen bonding and hydrophobic or electrostatic interactions http://www.japsonline.com/admin/php/uploads/1060_pdf.pdf.
- Chemically cross-linked nanogels: These nanogels are synthesized from hydrophilic polymers or amphiphilic copolymers held together by strong ionic and covalent bonds. Strength of these linkages is mainly dependent on type of functional groups present in the nanogels network http://www.japsonline.com/admin/php/uploads/1060_pdf.pdf.
Synthesis of Nanogel
Nanogels can be synthesized either by self-assembly of polymeric precursors using modified pullulan technique or heterogeneous polymerization of monomers. The polymerization methods include;
- Photolithographic techniques https://www.ncbi.nlm.nih.gov/pubmed/14570447
- Emulsion Polymerization Technique (EPT)
- Reverse microemulsion polymerization technique
- Inverse miniemulsion polymerization technique https://pubs.rsc.org/en/content/articlelanding/2010/py/c0py00010h#!divAbstract
- Free radical crosslinking polymerization technique https://www.researchgate.net/publication/224049479_Size_optimization_of_biodegradable_fluorescent_nanogels_for_cell_imaging
Mechanism of Action
The emancipation of carrier molecules (drugs, therapeutics, vaccines or hormones) entrapped inside nanogel particles depends upon various factors, i.e. pH, temperature and light etcetera.
pH responsive mechanism:
While using pH sensitive nanogels as delivery systems, the carrier molecules are released at the exact site within the body of patient where pH for a particular type of nanogel is optimum. Polymers employed in the synthesis of such nanogels contain pH sensitive functional groups that ionize or deionize at specific pH resulting in increased osmotic pressure, swelling and porosity of polymers which triggers the release of carrier molecules https://nebraska.pure.elsevier.com/en/publications/nanogels-as-pharmaceutical-carriers-finite-networks-of-infinite-c.
Temperature responsive mechanism:
Temperature sensitive nanogels are reactive at a particular temperature known as volume phase transition temperature (VPPT) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3086585/. Above and below this temperature, nanogel particles shrink or swell respectively and consequently their contents squeeze out. The change in volume of these particles is abrupt that can rupture cellular network of a patient body. Nanogels made from chitosan are thermosensitive. They are used in hypothermic cancer treatment.
Light responsive mechanism:
Light responsive nanogels contain specific photosensitizers. When exposed to light, these sensitizers produce ROS (reactive oxygen species) that subsequently leads to oxidation of cellular membranes. As a result, the therapeutic agents are released into cytoplasm https://innovareacademics.in/journal/ijpps/Vol4Issue3/4317.pdf.
Applications of Nanogels
- Nanogels are an advanced application of nanotechnology. Due to their versatile properties, they can be used in treatment of various cancers and autoimmune diseases. Nanogels with high biocompatibility and biodegradability features assure the favorable drug delivery in body preventing accumulation of nanoparticles or polymers in the organs and avoiding any immunological responses. They can easily penetrate the blood brain barrier and transport drugs to the brain.
- Some nanogels comprises of distinctive functional groups that help in targeted drug transport and release within the body by binding the functional groups with the specific antibodies. They also prevent the binding of antibodies with non-targeted tissues.
- Nanocarrier based drugs delivery system (DDSs) increases the bioavailability of drugs in cancer therapy as they specifically invade the tumors and then release drugs within them.
- Nanogels can also be used to deliver vaccines in the body. The constituents of nanogel protect vaccine from enzymatic degradation https://kclpure.kcl.ac.uk/portal/en/publications/polymeric-nanogels-as-vaccine-delivery-systems(6c29fa48-8761-4e4b-95ef-ee3752aa9bb5)/export.html.
Nanogels are three-dimensional, nanosized particles or fabrications synthesized from natural or synthetic polymers through a variety of techniques. They can be classified into various groups on the basis of the type of cross-linking present in them or their response towards specific stimuli. Due to the remarkable physical and chemical properties of nanogels, they are used in medical science as efficient therapeutic carriers for vaccines, drugs and biological molecules.
Nanogels are highly target specific and are more effective against cancers, neurodegenerative disorders and autoimmune diseases as compared to traditional drug delivery systems.
This article is jointly written by Hamna Younus, Sabahat Iftikhar and Zainab Masood from Department of Biotechnology, Kinnaird College for Women, Lahore