Role Of Nano Medicine In Managing Rheumatoid Arthritis

Introduction

Rheumatoid arthritis is an autoimmune disease, progressive in nature, affecting 1% of the population in which the ratio of women is three times more than men. Rheumatoid Arithrits is a chronic inflammatory disease. The function of inflammatory response is to prevent the tissues from infection. Acute inflammation, involves activation of inflammatory mediator and recruitment of monocyte for the removal of pathogens whereas when the inflammation trigger is persistant or non-resolving it’s likely to cause a chronic inflammation. Chronic inflammation is an induction of proinflammatory and infilteration of mediators leading to tissue damage. Rheumatoid arthritis is characterized by inflammation of synovial fluid leading to bone deformation erosion and loss of activity. Clinical manifestation of RA are, the presence of anticitrullinated protein antibody (ACPA and rheumatoid factor (RF)) in the blood, joint tenderness, muscle soreness and increased risk for pulmonary, cardiovascular disease and skeletal disorders. Also there is finding of involvement of HLA genes and other genes. However, the etiology has not been understood completely. Some other factors which can lead to chronic inflammation are genetic factors and environmental triggers as well as adaptive immune response.

Nanomedicine is a branch of nanobiotechnology that applies the data and tooling for prevention, diagnosis, treatment and cure of a disease. However most of the diseases can be controlled but not cured. Biocompatible and biodegradable Disease modifying antirheumatic nanomedicine (DMARNs) gives a promising strategy for RA.

The currently available treatments for this progressive disease are immunosuppressive drugs, anti-inflammatory drugs including NSAIDs and corticosteroids. To promote self-targeting drug loaded carriers are coupled with DMARNs which in turn minimizes the amount of drug required to control articular inflammation. Nanomedicine are not just limited to dendrimer, liposomes, PEGalyted liposomes, niosomes, polymersomes, biological agents and hydrogel nanoparticles. They can be designed with lipid and polymer and sometimes even the use of inorganic nanostructures which are used for intravenous administration providing a better therapeutic approach for rheumatoid arthritis

Current conventional Drugs and Drawbacks

There is no standard treatment for joint inflammation until now. The treatment procedure utilized incorporates immunosuppressives that have a few symptoms. Tofacitinib, methotrexate (MTX), leflunomide, furthermore, hydroxychloroquine have been ordinarily utilized for joint pain treatment.

Acetomorphine is cheaply available drug which is used to reduce fever and mild to moderate pain. The risk associated with the drugs is its availability as it’s an OTC and found in hundreds of prescription making its consumption easy and frequent ultimately leading to liver damage.

Opioids are the strong pain killers which comes under schedule H. Taking opioids for longer periods of time can result in development of tolerance and physical dependence other risk associated with opioids are constipation and dizziness.

NSAIDs are principally used to decrease minor inflammation and pain in any case, they don't lessen joint pain and are related with significant symptoms including gastrointestinal bleeding, expanded risk of heart attack and fluid retention in the body.

Corticosteroids are anti-inflammatory drugs. They are used for bridging therapy with others. For persistence treatment corticosteroids are given as low dose therapy and for sudden treatment or flashes they are given as high dose therapy. The risk of steroids is associated with the direction and the time period (for how long you take it) their use is limited because of their tendency of causing suppression of adrenal glands, intolerance to glucose and increased susceptibility to other infections.

DMARDs incorporate methotrexate (MTX), sulfasalazine and leflunomide. Early presentation of these operators has been appeared to give an increasingly ideal result in patients, and they are known to diminish disease progression. Their function is to ease symptoms, slow the disease progression and reduced inflammation of joint. They are too associated with different adverse effects which include GIT complications, hematologic adverse events and toxicity of liver

Delivery system to overcome drawbacks

Drug delivery system is a formulation, or an approach for introducing a pharmaceutical product into the body mostly in the form of nanoparticles to achieve a desired therapeutic response it improves the efficacy and safety of the drug by rate controlling and the extent of release of a drug from a particular dosage form in a given time period.

The drug delivery system is further classified as Modified release drug delivery system-controlled or sustained release DDS, Vesicular DDS and Particulate DDS,

Drug delivery systems available for rheumatoid arthritis are DMARNs, Micelles, nanoparticles, nano and micro carriers, dendrimers, liposomes, lipogelosome, emulgels, glucocorticoids.

Nanoparticles: Nanoparticles system relies on polymers and is most commonly preferred route of DDS. Nanoparticle may range from 1 to 100 nm. They are categorized into two, nanoencapsules and nanospheres To control the release of encapsulated drug and circulating time most researchers prefer PLGA nanoparticles because they are most effective in reducing the inflammation. several advantages associated with nanoparticles are Reduced dose frequency, Enhanced solubility, Prolonged release of drug, Modified pharmacokinetic properties, Tissue drug distribution and Reduced toxicity

Dendrimers: Dendrimers, commonly known as starbust dendrimers, are cascade molecules, highly branched artificial macromolecules which are monodipersed in nature. They are the new class of polymeric materials. Globulus structure of dendrimer provide a large number of surface groups which increases the loading of drug. The benefits of utilizing dendrimers are site targeting, controlled release of drug and increased drug loading capacity however the presence of amino group could result in toxicity thereby limiting its use.

Micelles: Micelles are the delivery system which are utilized for treatment of RA. Since, stability of micelles is a serious issue to be considered. So as to check the solubility as well as stability, these were planned with PEG phospholipids that are been utilized for encapsulation of drug. Merits associated with this delivery system are great physicochemical stability, increment in the solubility, increased efficiency and Reduced lethality.

Liposomes: Liposomes are biodegradable and biocompatible concentric bilayer vesicles made up to natural lipids, in which the aqueous core is entirely enclosed by a membranous lipid bilayer. Sometimes liposomes are administered intravenously to improve the efficacy of RA by getting deposited in synovial tissue. The size usually ranges from 20 to several micrometers. Advantages: increased stability, selective passive targeting, reduced toxicity with increase efficacy.

Microemulsion: The Micro emulsion is topically controlled colloidal dispersions comprise of thermodynamically steady system which are administered at the affected inflammation site. Its molecule size is from 10-100nm.

Overview of Novel Drug Delivery System

Vesicular Drug Delivery System

Liposomes: They are concentric bilayer vesicles made up of natural lipid. Liposomes are classified based on their structure parameter (MLV, OLV, ULV, Multivesicular vesicles) passive loading or active loading techniques are preferred for preparation of liposomes. Passive loading includes solvent and mechanical dispersion method and detergent removal. Stealth liposomes, immune liposomes, cationic liposomes, lactoferrin loaded liposomes, superoxide dismutase liposomes, clondronate loaded liposomes are prepared for treating Rheumatoid Arthritis

Niosomes: They are unilamellar and multilamellar bilayer vesicles of non-Ionic surfactant which may or may not include cholesterol. They are similar to liposomes but are osmotically more active and stable. The structural classification of niosomes is similar to liposomes however they are also classified according to their sizes; small niosomes ranging from 100 nm to 200 nm, niosomes having a range of 800nm to 900nm are considered as large and the size for big niosomes ranges from 2um to 4um. Niosomes have risen as a medication to stack sulfasalazine which is utilized in treatment of progressive disease. It is done employing the method of thin film hydration method, involving hydration condition of 24 hrs at temperature of 30-35°C which should be maintained to get the maximum yield.

Controlled release drug delivery system

Dendrimers: New artificial macromolecules which have better water solubility, biocompatibility and bioavailability. Dendimers nanostructure give considerable advantages such as accessible cell entry, targeted drug delivery and no obstruction across biological barriers. Phosphorus-containing dendrimers capped with anionic azabisphosphonate (ABP) end groups prompt anti-inflammatory activation of human monocytes. Dendrimers can be preparation of dendrimers include convergent method and divergent method. Divergent method initiated from the central of the core and extend till surface whereas convergent method uses top to down method.

Microemulsion also known as modern colloidal drug delivery system. Tenoxicam is the microemulsion formulation used for treatment of rheumatoid arthritis its prepared using oleic acid as oil tween 80 as surfactant and n butanol and ethanol as co surfactant. microemulsion is prepared by dissolving the drug in oil phase and water phase is mixed with surfactant and afterward cosurfactant is included gradually with consistent blending until it becomes transparent. Later both the phases are mixed together and desire microemulsion can be achieved by using pseudo ternary phase diagram. At last, allow the solution to equilibrate.

Particulate release drug delivery system

Nanoparticles: For the treatment of rheumatoid arthirits FDA used both metallic and gold particles nanoparticles mostly PGLA bethamethasone is used as nanoparticle for reducing the inflammation. ploymerisation, ionic gelation and performed polymers are the techniques of preparation of nanoparticles. General method for preparation of polymeric nanoparticles are solvent evaporation, dialysis, salting out, solvent diffusion nano precipitation

Nanosponges: Nanosponges have been developed in San Diego which can be absorbed safely and neutralizes the wide variety of protein that are involved in progression of the disease. For the preparation of neutrophil nanosponges, A procedure is done for neutrophils to get them separated from whole blood. After this processed cells are placed in a mixture that causes the swelling and bursting phenomenon, leaving the membranes residues, further the membrane is fragmented into smaller pieces. Mix them with the spherical nanoparticles made up of biodegradable polymer fused the neutrophil cell membranes onto the nanoparticle surfaces.

Conclusion

There is an expanded intrigue and uses of novel drug delivery system in treating Rheumatoid Arthritis and other chronic diseases. The continuous advancement of nanomedecine which are biocompatible and other delivery system for current antirheumatic specialists may at last lead to bring down effective doses, diminished dose frequency furthermore, increasing effective l treatments with less foundational symptoms. Novel drug delivery system has several advantages over conventional DDS.

The release of drug from conventional dosage form is immediate thus causing the fluctuation in plasma drug concentration with novel drug delivery system we can control the release of a dosage form at a predetermined rate and thus controlled the fluctuation in plasma level.

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