1. INTRODUCTION:

In recent decades, the field of biomedicine has witnessed significant advancements in nanotechnology, leading to the emergence and increasing popularity of nanocarriers. These nanocarriers not only possess the ability to encapsulate routine chemotherapeutic agents but also serve as versatile platforms for multifunctional diagnosis, combinational therapy, and theranostics.¹ The term "Nanogel" refers to a nanoparticle composed of a hydrogel and a network of cross-linked hydrophilic polymers.² Natural substances with various molecular origins offer a starting point for the development of new medications. The interest in creating synthetically accessible lead compounds that mirror the chemistry of their counterparts has recently emerged as a trend in the identification of drugs based on natural products.³ There is currently a rapid surge in interest for exploring new applications of medicines, with a particular emphasis on diagnostic methods and enhancing existing therapies.⁴

Nanogels possess the capability to transport enclosed drug molecules to specific tissues or cellular structures while maintaining the integrity of the drug and preventing premature release into the bloodstream or other surrounding tissues.⁵ Due to facilitate the creation of NGs, which are thought to be more appropriate for optimal delivery to the target place due to their small size, nanotechnology has advanced. simple formulation, longer retention period, and swelling properties.⁶ Nanogels have good biocompatibility, making them comparable to biological tissues. Drugs that are hydrophobic or hydrophilic can be enclosed inside the 3D framework. This prevents drug deterioration during storage or blood circulation (such as hydrolysis or enzymatic breakdown) and lowers the risk of adverse drug reactions.⁷ When Nanogels are combined into aqueous solutions, their swollen networks become pliable and can hold the required quantity of water. In order to load desired biological or pharmacological molecules into the Nanogels and create highly distributed hydrophilic particles, the polymer matrix and the agents must be given an opportunity to make spontaneous relations. The resulting structure is able to prevent degradation of the intended loaded biomolecule.⁸

Routes of Administration of Nanogels:

· Oral

· Pulmonary

· Nasal

· Parenteral

· Intra-Ocular

· Topical.⁹

Scheme 1: Multifunctional nanogel for biomedical application in drug delivery

2. CLASSIFICATION OF NANOGELS:

There are two primary types into which nanogels are frequently categorised. Based on their responsive behavior—which might be either stimuli-responsive or non-responsive—the initial classification is made. Non-responsive microgels just swell after absorbing water, in this case.

1. When exposed to environmental changes such temperature, pH, magnetic field, and ionic strength, stimuli-responsive nanogels swell or deswell.

2. Multi-responsive nanogels react to a variety of environmental cues. The second classification of polymeric gels (including nanogel) is based on the types of connections that are present in the network chains of gel structure.¹⁰

2.1 Physical crosslinking:

During the preparation of nanogels, the sizes of these supramolecular particles, composed of polymer molecules formed through noncovalent interactions, can be altered by adjusting factors like polymer concentration and various environmental conditions including ionic strength, temperature, and pH.¹¹

Types of physical crosslinked nanogels¹²

Table No 1: Types of physical crosslinking nanogels

Nanogels	Examples
Hybrid	The hybrid composite consists of nanogel particles that are dispersed in organic or inorganic matrices. These particles have the ability to form complexes with various proteins, drugs, and DNA. They can also coat the surface of liposomes, particles, solid surfaces, and even cells. This composite is capable of delivering insulin and anticancer drugs effectively. A key component of this composite is cholesterol-bearing pullulan, which is composed of a pullulan backbone with cholesterol branches. Through the association of hydrophobic groups, the molecules self-aggregate and form stable nanogels via physical crosslinking points. The nanogel can be formed in an aqueous medium through self-assembly or aggregation of hydrophobized polysaccharides, hydrophobized pullulan, and pullulan-poly(N-isopropylacrylamide).
Micellar	In aqueous solutions, amphiphilic block or graft copolymers can be self-assembled supramolecular to form structures characterized by core-shell morphology. These structures are formed through hydrogen bonds, with a hydrophobic block segment comprising the core and a surrounding shell composed of a hydrophilic polymer block that provides stability to the complete micelle. The core of the micelle offers sufficient space for encapsulating drugs or biomacromolecules, protecting the drug molecules within the hydrophobic core from hydrolysis and enzymatic degradation. Micelle systems based on N-isopropylacrylamide have been investigated as drug delivery devices.
Liposomes Modified	Under a pH of 5.5, liposomes that carry succinylated polyglycidol undergo chain contraction and are capable of delivering calcein to the cytoplasm. Additionally, liposomes modified with poly(N-isopropylacrylamide) have been studied as temperature and pH sensitive nanogels for transdermal drug delivery.

2.2 Chemical crosslinking:

2.2.1. Inverse Emulsion Polymerization:

Applying proper emulsification methods, nanogels can be synthesised in the presence of an oil soluble emulsifier. The concentration of the monomer and crosslinker, as well as the pH of the reaction media, all have an impact on the size of the nanogels during inverse emulsion polymerization.⁷

2.2.2. Reversible addition–fragmentation chain transfer (RAFT) polymerization:

A polymer is subjected to a series of reactions with dithioester compounds by RAFT; these reactions regulate the molecular mass of the polymer during free radical polymerization and include reversible addition, reversible degradation of adducts, and chain transfer reactions. Amphiphilic polymers can have their length, configuration, and features changed via RAFT technology, altering the micelle structure.¹³

2.2.3. Free radical crosslinking polymersization technique:

A vinyl-containing fluorescent prepolymer was crosslinked using free radicals to generate photocrosslinked biodegradable photoluminescent polymers (PBPLPs) nanogel for drug delivery and cell imaging. The development of a PBPLPs nanogel heralds a new era for theranostic nanomedicine's development of nanobiomaterials for drug delivery and cell imaging.¹⁴

2.2.4. Stimuli –Responsive Behavior

The past few years have seen a significant increase in the use of responsive nanogels as smart drug delivery systems for controlled drug release and cancer treatment applications, giving prolonged and enhanced control of administration of drugs. The nanosystems' responsive behaviour involves a number of reactions, including receiving an external signal (physical or chemical), changing the material's characteristics or reacting chemically with it, and then transducing those changes to cause the cargo to be released. Studies on the release of the payload from the interior volume of the nanogels under the impact of pH, temperature, ionic strength, and light have been published.¹⁵

Scheme 2: Schematic representation of mechanism of drug release from nanogels

3. APPLICATION:

1. Auto immune disease:

A new nanogel drug delivery system for the immunosuppressant mycophenolic acid (MPA) was developed, constructed, and tested in this work. The study has concluded that local medication delivery based on nanogels is more effective at treating lupus erythematosus because it specifically targets antigen-presenting cells. This innovative method of medicine delivery prolongs patient survival and prevents renal damage, a frequent symptom of lupus^.4

2. Bleeding:

Proteins can be synthesised into nanogels and utilised to stop bleeding because of their capacity to self-assemble at the nanoscale level^.16

3. Neurodegenerative Disease:

Alzheimer's disease and Parkinson's disease currently lack a well-known cure; as a result, when oligonucleotides demonstrated the potential to be used as a diagnostic or therapeutic tool for these diseases, they were the main focus of numerous studies. Because oligonucleotides are unstable against metabolism, unable to cross the blood-brain barrier, and quickly eliminated by excretory organ excretion, their use in the treatment of neurodegenerative disease has been significantly hampered thus far. improving the performance. They were included into nanogel delivery systems of oligonucleotides. By enabling oligonucleotides to pass the blood-brain barrier, nanogels' unique characteristics facilitate their distribution into the central nervous system^.17

Scheme 3: Applications of nanogel

4. LIMITATIONS:

Adverse effects may occur in the body if any traces of polymers or surfactant remain, which adds to the challenge of removing the surfactant and solvent at the end of the preparation process.¹⁸ However, the manufacturing process itself is not very expensive. The efficiency of drug loading demonstrated by nanogels is limited.¹⁹

5. FUTURE VISION:

Nanoparticle-based gels, functioning as a transporter framework, have evolved over time to encapsulate various types of guest atoms. This capability stems from advancements in their synthesis methods and a deeper understanding of their material properties, including softness and expansion characteristics. With this understanding, we can explore their applications in various fields and the potential to modify these properties for our advantage.³ The findings confirmed the lipogel's structure and thoroughly explained its unique features, indicating that lipogel may be utilised as drug delivery vesicles. When the anticancer drug 17- DMAPG was first studied, lipogels were initially shown by 80 to be a viable drug delivery technique.²⁰

6. CONCLUSION:

Nanogels may be able to solve some of the problems with conventional and current medicines, including their lack of consistency and nonspecific adverse effects. Nanogels seem to be an attractive option for numerous targets, including the brain, lungs, colon, skin, GIT, and heart, with considerable advantages over alternative administration methods. Nanogels offer a variety of features that enable them to transport biologically active compounds, particularly biopharmaceuticals, at a low cost. Nanogels are used to deliver active pharmaceutical ingredients under regulated conditions. Future research in this area should focus on creating nanogels with superior targeting residues to change highly selective absorption into specified cells. This might be especially important when trying to target cancer cells and prevent non-specific absorption into healthy cells. To confirm the use of this delivery system on a person, extensive in vivo and in vitro studies should be needed. Thanks to recent advancements in nanogel development, there is a promising future for nanogels in the treatment of autoimmune disease, bleeding, and neurological disorders. The broad application of commercial nanogel formulations is responsible for the current success of nanogel-based drug delivery systems.

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Received on 20.07.2023 Modified on 14.08.2023

Asian J. Pharm. Tech. 2023; 13(4):293-296.

DOI: 10.52711/2231-5713.2023.00052