A Review- Nanogel Drug Delivery System

Saurabh Tiwari*, Shweta Singh, Dr. Pushpendra Kumar Tripathi, Mr. Chetan Kumar Dubey

Rameshwaram Institute of Technology and Managemnt, Lucknow, U.P

*Corresponding Author E-mail: tiwari.saurabh252@gmail.com

 

ABSTRACT:

Nanogels are one of the techniques in nanotechnology which has been most popular in effective drug delivery inside the body as well as topical treatment. Certain properties of nanogels make them suitable to carry different types of molecules like DNA, proteins, oligonucleotides, RNA, dyes, quantum dots and certain chemical agents like diclofenac to the target site. Its nano-sized structure has showed the reduced effect of toxicity of drug molecule as well as it provides controlled release of drug at the target site, increased the bioavailability of the drug. Besides it, nanogels have increased the life span of drugs in the body to enhance its effective results for the treatment of desired disease.

 

KEYWORDS: Nanogels, diclofenac, nanotechnology, topical treatment.    

 

 

INTRODUCTION:

Nanotechnology, a relatively novel technique, offers a broad scope for a smart drug delivery and drug manufacturing (nanomedicine) approach involving the design, synthesis and characterization of materials or molecules and devices that have effective function at nanometer scale. This technique mainly focuses on the radiacal improvements in the current therapeutic and diagnostic procedures. Development of novel nano-sized particulate drug delivery systems (DDS) have shown the profound impact on disease prevention, diagnosis, and treatment as reported after the researches in academic laboratories and pharmaceutical companies all over the world. This technique have overcome the challenges by enhancing absorption of drugs, reducing toxicity of drugs, controlled release of doses and reducing biodegradation. It has also reduces the chances of activation of immune cells upon administration of drugs inside the body.

 

Various nanotechnological techniques like protein based nanoparticles, lipid based nanoparticles, nanoemulsions, nanocrystals, nanodiamonds, carbon nanotubes, nanosuspensions and nanogels have been introduced as an advanced DDS in which nanogels have been introduced in the market due to its maximum advantages over other DDS techniques (2)(5)(6). Nanogels (nanosized hydrogels) are physically or chemically cross-linked, swollen small particles which are made up of flexible hydrophilic or amphiphilic polymer networks. These polymer networks can be anionic or ionic. They behaves as a carrier molecule for drugs and designed in which a way that they can easily absorb biologically active compounds by the formation of biomolecular interactions like salt bonds, hydrophobic or hydrogen bonding. They are designed in such a way that these nanogels can easily encapsulate diverse class of biomolecules by optimizing the molecular composition, size and morphology, to ensure the controlled release of drug molecule in vivo. When nanogels dispersed in the aqueous media, their swollen networks become soft and are able to encapsulate a required volume of water.

 

 

Fig. 1: Model showing releasing of Drug from Nanogel

 

Desired biological or drug molecules can be loaded into the nanogels by allowing the formation of spontaneous interactions between the polymer matrix and the agents; resulting in the formation of highly dispersed hydrophilic particles. This resulting structure is able to provide physical protection to the desired loaded biomolecule from degradation. Therefore, nanogels are a kind of versatile structure for both drug encapsulation and drug controlled release on the target site (3) (5) (7) (8).

 

Nanogels, during the first decade of its development, have been proved to be a potential structure for systemic drug release, designing of multifunctional nanocarriers like theranostics and controlled drug release at the target site.

 

Due to the large surface area and adjustable sixe of nanogels, these molecules are able to incorporate different molecules.

 

Table 1: Types of nanogels and polymers used in the treatment of diseases

Polymer

Type of Nanogel

Acetylated chondroitin sulfate

Self organizing nanogel

Cross linked polyethyleneimine and PEG/pluronic

Biodegradable nanogel

Glycol chitosan grafted with

3-diethylaminopropyl groups

pH-responsive

Pullulan/folate-pheophorbide

Self quenching polysaccharide based

Crosslinked branched network of polyethyleneimine and PEG

Polyplex nanogel

Polyethyleneimine nanogels

Size dependent property nanogel

Cholesterol bearing pullulan nanogels

Sustained release nanogel

Reducible heparin with disulfide linkage

Reducible nanogel

Pluronic polyethyleneimine/DNA complex

Temperature responsive and volume transition nanogels

Acetylated hylauronic acid

Specific targeting nanogel

Polyacrylamide

Novel core shell magnetic nanogel

Reference: Sultana et al. / Journal of Applied Pharmaceutical Science 3 (8 Suppl 1); 2013: S95-S105

 

According to the researches it has been observed that drugs involving DNA/RNA and inorganic molecules are incorporate in cases of delivering drugs at the site of brain. Molecules like polyethyleneglycol (PEG) and polyethylenimine when embedded in a nanogel has been proved that this composition is able to cross the blood-brain barrier and deliver oligonucleotides to the brain. Polyelectrolyte nanogels possess a property which can easily incorporate oppositely charged low molecular mass drugs or biological macromolecules like phosphorylated nucleoside analogs, siRNA (for anti-cancer and anti-viral treatment), DNA, proteins, oligonucleotides, which bind to the nanogel ionic chains and phase separate within the finite volume of nanogel. Nanogels are also used to deliver molecules like quantum dots, imaging agents and dyes because of its multiple chemical functionalities (5) (6) (7).

 

Nanogels for Anti-inflammatory Drug Delivery in Skin Diseases:

For effective drug delivery in skin inflammatory diseases, a skin permeating nanogel system (SPN) have been developed that is composed of a surface of modified polymeric bilayered nanoparticles along with a gelling agent. In this SPN, Poly-(lactide-co-glycolic acid) and chitosan were used to prepare bilayered nanoparticles (NPS) and oleic acid (NPSO) was used to make modified surface. For nanogel formation, hydroxypropyl methyl cellulose (HPMC) and carbopol was used after maintaining the desired viscosity. These researches have showed the effective percutaneous delivery of drugs in case of skin diseases (9).

 

Diclofenac, a non-steroidal anti-inflammatory drug (NSAID), is mainly used in cases of arthritis. According to the research evidences, hydrogels of diclofenac sodium liposomal gel have better outcomes as an anti-inflammatory agent (4).   

 

Nanogels as a Cure for Brain Diseases:

Nanogels have been identified as a successful carrier for oligonucleotides to the brain by using polarized monolayers of bovine BMEC. According to the researches, the model of blood brain barrier has showed the increased level of oligonucleotides across the cell monolayers due to the incorporation with nanogels. Nanogels modified with insulin or transferring ligands have showed the further increased transport of oligonucleotides. Besides it, these nanogels have showed no adverse or toxic effects on the model mice (2).

 

Nanogel Based Drug Delivery in Systemic Lupus Erythematosus:

In case of systemic lupus erythematous, a novel nanogel vehicle for the delivery of immunosuppressant mycophenolic acid (MPA) was developed. In the model of lupus-prone mice, the MPA-loaded nanogel was tested that showed the increased levels of median survival time (MST) by three months with prophylactic use (MST was 50 weeks versus 38 weeks without treatment with MPA-loaded nanogel) and by two months after administration in case of severe renal damage (MST was 12.5 weeks after proteinuria onset versus 4 weeks without treatment). This nanogel treatment resulted in enhancing the biodistribution of drugs to the organ and association with immune cells (10, 11).  

 

Protein Nanogels:

Research has reported that hen egg white proteins ovalbumin and lysozyme have been prepared as a nanogel. In this novel method, solution of ovalbumin and lysozyme with pH 5.3 adjusted upto the pH 10.3 was stirred and heated. As the nanogels have spherical and core-shell shape, the core was designed with lysozyme and shell comprised of ovalbumin. These proteins were in denatured states, bounded by intermolecular hydrophobic interactions, hydrogen bonds and disulfide linkages. The charges on nanogels can be adjusted with the pH of the medium. The surface structure of the nanogel can be stabilized with the help of electrostatic repulsive force. Alkali has been used in the formation process of these nanogels so that it can be made edible and nutritional. Besides it, solution of these types of nanogels are very stable for long time storage and can also be stored as lyophilized powder; making it more applicable (1). 

 

Benefits of Nanogel Drug Delivery Approach:

1.       It provides protection from biodegradation of drugs inside the body.

2.       Physical properties like size of nanogels can be easily adjusted and maintained according to the desired delivery molecule.

3.       Low amount drug is required as well as quantity of doses is reduced.

4.       Improves the bioavailability of the drug molecule and reduce the toxicity of the drugs.

5.       Drugs loaded nanogels can be delivered inside the body with no adverse or side effects as well as can be applied topically.

6.       These are able to cross blood barin barrier as well as physiological barrier like skin.

 

Drawbacks of Nanogels:

1.       It requires expensive techniques to completely remove the solvent sand surfactants at the end of the process.

2.       Sometimes, traces of surfactants can cause toxicity.

 

CONCLUSION:

Nanogels are effective and novel drug delivery system that has improved the traditional drug delivery system and appeared to be a best drug delivery vehicle for various drug biomolecules or molecules. Future researches can be conducted to study about its improved designs, targeting properties to enable highly selective uptake into the desired organs. 

 

REFERENCES:

1.     Shaoyong Yu, Ping Yao, Ming Jiang, Guangzhao Zhang (2006). Nanogels Prepared by Self-Assembly of Oppositely Charged Globular Proteins. Biopolymers. 148-158: 83.

2.     Hamsaraj Karanth and Rayasa S. Ramachandra Murthy (2008). Nanotechnology in Brain Targeting. International Journal of Pharmaceutical Sciences and Nanotechnology. 9-24: 1(1).

3.     Koen Raemdonck, Joseph Demeester and Steefan De Smedt (2009). Advanced Nanogel Engineering for Drug Delivery. Soft Matter. 707-715: 5.

4.     A. V. Jithan and M. Swathi (2010). Development of Topical Diclofenac Sodium Liposomal Gel for Better Anti-inflammatory Activity. International Journal of Pharmaceutical Sciences and Nanotechnology. 986-993: 3(2).

5.     Serguei V. Vinogradov (2010). Nanogels in the Race for Drug Delivery. Nanomedicine. 165-168: 5(2).

6.     Nilesh Jain, Ruchi Jain, Navneet Thakur, Braham Praksh Gupta, Deepak Kumar Jain, Jeetendra Banveer, Surendra Jain (2010). Nanotechnology: A Safe and Effective Drug Delivery System. Asian Journal of Pharmaceutical and Clinical Research. 159-165: 3(3).

7.     Alexander V. Kavanob and Serguei V. Vinogradov (2010). Nanogels as Pharmaceutical Carriers: Finite Networks of Infinite Capabilities. National Institute of Health- Public Access.

8.     Dhawal Dorwal (2012). Nanogels as Novel and Versatile Pharmaceuticals. International Journal of Pharmacy and Pharmaceutical Sciences. 67-74: 4(3).

9.     Punit Shah, Pinaki Desai, Apurva Patel and Mandip Singh (2012). Skin Permeating Nanogels for the Cutaneous Co-delivery of Two Anti-inflammatory Drugs. National Institute of Health- Public Access.

10.  Farhana Sultana, Manirujjaman, Md. Imran-Ul- Haque, Md. Arafat, Sanjida Sharmin (2013). An Overview of Nanogel Drug Delivery System. Journal of Applied Pharmaceutical Sciences. 95-105: 3(8 Suppl 1).

11.  Michael Look, Eric Stern, Quin A. Wang, Leah D. DiPlacido, Michael Kashgarian, Joe Craft and Tarek M. Fahmy (2013). Nanogel-Based Delivery of Mycophenolic Acid Ameliorates Systemic Lupus Erthymatosus in Mice. The Journal of Clinical Insvetigation. 1741-1749: 123(4).      

 

 

Received on 24.10.2015          Accepted on 09.11.2015        

© Asian Pharma Press All Right Reserved

Asian J. Res. Pharm. Sci. 5(4): Oct.-Dec. 2015; Page 253-255

DOI: 10.5958/2231-5659.2015.00037.5