Introduction

Rheumatoid arthritis, also referred to as (RA) is a form of autoimmune disease that causes pain in the joints and destruction. It affects 0.3-1.0% of the global population, including up to 0.75% in India. RA raises the risk of cardiovascular disease and mortality, but traditional risk factors alone don’t fully account for this link. The death risk among those with rheumatoid person is 1.5 times greater than that of a normal healthy individual. It affects between 0.5% and 1.0% of individuals, with women having a fourfold higher prevalence than men. It is used to cover a range of disorders, including symmetrical, continuous, and destructive polyarthritis, some of which include rheumatoid factor involvement &/or positive tests of anti-cyclic citrullinated peptide (anti-CCP) antibodies. RA pathogenesis may begin at the mucosal level, with studies linking smoking and lung abnormalities to RA development, where bronchus-associated lymphoid tissue produces ACPA and RF. Early RA patients show reduced lung microbiota diversity, with overrepresentation of the genus Pseudonocardia, while sputum from at-risk individuals contains RA-related autoantibodies, indicating the lungs as a primary site of autoantibody production. Transdermal administration delivery of drugs systems (TDDSs) offers a viable treatment option for RA by reducing adverse effects, increasing bioavailability, and simplifying self-administration. This illness provides considerable hurdles because existing therapy techniques largely offer symptomatic alleviation, and the goal of total healing remains elusive. When medications are ineffective, surgery is the last resort, but recent treatment advancements have greatly improved patients’ quality of life by slowing disease progression. ¹

Limitations of conventional RA therapies (e.g., systemic side effects, poor target specificity)

Conventional treatments for RA, whereas successful in treating symptoms and reducing disease progression, have many major limitations. Conventional RA therapies can cause systemic side effects, including: NSAIDs can cause gastrointestinal ulcers, renal damage, and increased cardiovascular risk. Corticosteroids cause osteoporosis, excessive blood sugar, hypertension, & infections. Biologics: Raise the risk of severe diseases such as tuberculosis & opportunistic pathogens. This Conventional medicines sometimes lack accurate targeting mechanisms, resulting in poor target specificity. A greater dose is required for effective therapeutic efficacy, exacerbating adverse effects. Off-target impacts can damage healthy tissues. Sub-optimal bioavailability & pharmacokinetics: RA medications have inadequate solubility, poor stability, or quick clearance, requiring frequent doses and uneven therapeutic levels. Conventional therapy can struggle to reach therapeutic concentrations in inflammatory synovial joints due to low tissue selectivity. Prolonged usage of DMARDs and biologics can result in drug resistance or anti-drug antibodies, lowering their effectiveness. In that medicines fail to consider individual aspects such as genetics, illness severity, and comorbidities, resulting in unsatisfactory outcomes.²

Role of nanotechnology in overcoming these challenges

Nanotechnology facilitates the development of advanced nanomaterials, including “smart material” for targeted delivery of medicines and nanotechnology in cosmetics. As medicine, microscopic and nanoscale technologies improve medical therapy by enhancing medication delivery and allowing for quicker illness identification, which improves patient outcomes. Nanotechnology has altered the way that rheumatoid arthritis treatments by increasing medication absorption, specific aiming at, and controlled release of nanomaterials, resulting in fewer adverse effects. It has also paved the path for advances in targeted administration of drugs, attaches, and methods for diagnosis, with nanotechnology and photo thermal therapy holding tremendous potential for RA treatment. Nanotechnology is crucial within treating rheumatoid arthritis, improving implants, and creating diagnostic and treatment procedures in orthopedic medicine. It offers targeted medication administration, minimizes adverse reactions, boosts the concentration of drugs in joint organs, and reduces the progression of immune-related illnesses such as rheumatoid arthritis. Nanotechnology advances rheumatoid arthritis, also known management by improving drug delivery systems. It allows for the regulated release of drugs directly into afflicted joints, enhancing drug absorption and decreasing systemic adverse effects. This method not only improves therapy efficacy, but also enables more personalised and efficient RA care. Furthermore, nanotechnology improves diagnostics and monitoring, with the possibility for early detection and accurate treatment, resulting in better patient outcomes.³

This review focusses at the existing trends, difficulties, and future directions for nanotechnology -based drug delivery methods in RA therapy. It discusses the biology of RA and how nanotechnology can help address unmet needs for RA therapy. The article discusses key nanocarrier systems, their uses, and accompanying problems, as well as new trends and opportunities in personalised medicine. This article seeks to provide a detailed overview of nanotechnology’s potential to revolutionize RA therapy by evaluating recent breakthroughs and continuing research.

Rheumatoid Arthritis: Pathogenesis and Treatment Needs

Rheumatoid arthritis, is a multidimensional autoimmune condition caused by a complex interaction of genetic, environmental, & microbiological factors. Its pathogenesis includes the development of anti-citrullinated the peptide antibodies, which cause mediated by the immune inflammation, synovial hyperplasia, & progressive joint destruction. Cells from the immune system (T cells, B cells, mast cells, dendritic & macrophages) & synovial cells (fibroblast and macrophage-like synoviocytes) are important participants in RA, as it involves the activation of inflammatory pathways that include JAK-STAT, MAPK, Wnt, and Notch. Auto reactive T cells as well as B cells increase immune responses by releasing cytokines and producing proteases such as the formation of matrix (MMPs), prostaglandins, &leukotriene’s, which cause tissue damage. Cytokines including TNF-α, IL-1, or IL-6 increase inflammation, inhibit regulating T cell activity, as well as promote angiogenesis, resulting in pannus development and joint damage. This all involved in fig 1.

Treatment Needs

Inflammation control involves the usage of DMARDs, biologics, & corticosteroids.

Targeted Drug administration: precise administration to specific tissues with little toxicity.

Long-Term Management: Reduce adverse effects and maintain efficacy.

Personalised treatment involves tailoring medicines to individual immunological profiles.

Mechanisms of disease progression (immune deregulation, joint inflammation, synovial hyperplasia)

Immune Dysregulation: The excessive stimulation of T-cells, B-cells are and macrophages causes’ excess release of cytokines (e.g., TNF-α, IL-6).

Joint Inflammation: Immune cells & cytokines cause chronic inflammation, which destroys synovial tissues.

Synovial Hyperplasia: The proliferation of fibroblasts in the synovial membrane produces invasive pannus tissue, which contributes to cartilage and bone loss. ⁴

Current Treatment Strategies for RA Pathogenesis:

DMARDs suppress immune activation while slowing disease progression. Biologics target pro-inflammatory cytokines like TNF-α and IL-6 to reduce inflammation.

Small Molecules: Block intracellular signaling routes (e.g., JAK inhibitor) to regulate immune responses and joint degeneration.

Unmet clinical needs and opportunities for advanced drug delivery systems

Precision Targeting: Direct distribution to inflamed regions to increase efficacy while reducing toxicity. Sustained release extends pharmacological effects for improved control and adherence.

Reduced side effects: Minimize the negative consequences of present medicines Innovative Systems: Use nanocarriers to increase bioavailability and control release. 

Figure 1: Pathogenesis of Rheumatoid Arthritis.5 Click here to view Figure

Nanotechnology in Drug Delivery: Concepts and Tools

Nanotechnology employs nanoscale materials (1-100 nm) for targeted medicine administration, controlled release, increased bioavailability, and decreased toxicity. It provides more precise therapy, increases efficacy, and promotes theranostic for personalised medicine.

 Key nanocarrier systems for RA drug delivery

Liposome

Liposomes have are spherical vesicles containing a core of fluid surrounded by several lipid bilayers. Liposomes are useful drug delivery vehicles due to its biocompatibility, biodegradable properties and ability to transport both small and big molecules, resulting in sustained release and stability across a variety of dosage forms and route of administration. In Rheumatoid treatment, nanocarriers in including liposomes and nanoparticles injected intra-particularly improve medication clearance while increasing patient compliance. A novel liposomal sulfapyridine prodrug shown significant reductions in joint swelling, discomfort, and inflammatory indicators in a rat arthritis model. Various types of liposome are categorize dand mention in fig 2.

Liposomes that contain antibody or fragments of antibody, allowing active targeting of certain cells and organs. Attacking CD4 T lymphocytes using drug-loaded anti-CD134 immunoliposomes has been found to improve results in antigen-induced arthritis. Magneto liposome that are tiny particles of iron oxide in liposomes that have been shown to be biocompatible and magnetophoretic. Mechanism of liposome involved in rheumatoid arthritis depicted in fig 3. They improve targeted medicine delivery in cancers and Rheumatism by using a magnet outside to raise drug concentration at the desired site Drug targeting concentrates therapeutic molecules at specific places by utilizing carriers that selectively target cells. Liposomes coupled with ligands, such as antibodies, boost efficacy while reducing adverse effects, with a variety of compounds being investigated for this technique.⁶ Various drugs are used through liposome drug delivery in rheumatoid arthritis mention in table 1.

Table 1: Liposome drug delivery used various form in rheumatoid arthritis.

Figure 2: Types of Liposome drug delivery  Click here to view Figure

Figure 3: Mechanism of Liposome involved in Rheumatoid arthritis Click here to view Figure

Dendrimers

Dendrimers have are highly branched, a three-dimensional polymeric nanocarriers that are formed through recurrent addition processes. They range in size from 1.1 nm (1.0G) to 9.8 nm (8.0G). Their enormous internal spaces allows the encapsulation of bioactive substances, which has the potential for regulated and prolonged medication release. Dendrimers have are hyper branched, monodisperse molecules with numerous end functional groups, providing great valency and adaptability for biomedical applications. Tomalia discovered dendrimers in 1985, identifying compounds after the Greek words for “tree” and “part”. Dendrimers have are three-dimensional in nature monodisperse macromolecules with very globular shapes.Different types of dendrimers are shown in fig 4.

Dendrimers are act like host-guest molecules called dendrite nets.Dendrimers, because of their nanoscopic length and monodispersity, are also known as arborols, cascades particles, dendrite atoms, or nanometric buildings throughout academia. These compounds include three fundamental components: the central core, branching parts, and terminating end groups. Growth begins at the centre, with branches forming from the repetitive addition of monomers, resulting in new generations, and culminating to groups of functions at the outer layer. Mechanism of dendrimers in rheumatoid arthritis is mention fig 5.

By the late 1980s, dendrimers have also been synthesize dutilizing the convergent approach. During this time, Vogtle and his associates, along with Tomalia and others, spearheaded the creation of hyper branched molecules, paving the way for dendrimer studies. These constitute biodegradable macromolecular nanoparticles characterized as having monodispersity and high drug loading capacity. These distinguishing characteristics make them ideal nanocarriers in for delivering bioactive drugs, increasing efficacy while lowering toxicity.¹⁵ In that rheumatoid arthritis variety of drug used to follow dendrimer drug delivery in table 2.

Table 2: Dendrimers drug delivery used various form in rheumatoid arthritis.

Figure 4: Types of Dendrimers Click here to view Figure

Figure 5: Mechanism of Dendrimer involve in rheumatoid arthritis. Click here to view Figure

Nanoparticles

Nanotechnology is a fast developing area that creates nanomaterials, with nanoparticle ranging from 1-100 nm and frequently possessing different features from their bulk counterparts. Nanoparticles, which are commonly made of metals such as copper, zinc, and gold, are utilized in medical treatments, industries, and everyday things such as cosmetics and apparel.

Nanomedicine uses sophisticated drug delivery methods to minimize side effects and provide optimal amount of drug at an intended site. Nanoparticles (NPs) provide therapeutic and imaging chemicals overall theranostic programs, with solid nanoparticles of lipid (SLNs) being preferred for safety. Multi-functionalization enhances targeted distribution and cellular penetration, whilst poly (ethylene glycol) (PEG) coatings facilitate bio-barrier clearance and macrophage uptake.  Nanoparticles drug delivery used in various form in given in table 3. Various types of Nanoparticles based on material composition and functionality are mentioned in fig 6.

Silver nanoparticles are potent antimicrobials that target bacteria, viruses, and various other microbes, making them useful for infection prevention. Silver nanoparticles, which are widely utilized as antimicrobial substances in textiles, water disinfection, and sunscreen products, have been successfully biosynthesized from plants such as the cannabis indica, Capsicum annuum, & Carica papaya. Gold nanoparticles, also called AuNPs, are utilized in immunochemical research, DNA detection, or antibiotic screening, whereas gold nanorods aid in cancer diagnosis by recognizing stem cells and microorganisms.²¹ Mechanism of action of nanoparticles in RA are given in fig 7. 

Table 3: Nanoparticles drug delivery used various form in rheumatoid arthritis.

Figure 6: Types of Nanoparticles. Click here to view Figure

Figure 7: Mechanism action of Nanoparticles in Rheumatoid Arthritis. Click here to view Figure

Nanomicelles

Nanomicelles are amphiphilic molecules or surfactant monomers that have a polar head and a lipophilic tail. The properties related with amphiphilic molecules in solution results in developmental structures termed as micelles. These micelles hold internally hydrophobic core and externally a hydrophilic surface.Types of Nanomicelles mention in fig 8. Nanomicelles are often utilized to speed up blood circulation, increase bioavailability, and target therapeutic drugs. Following systemic delivery, these medicines, packaged into nanocarriers as could selectively concentrate in inflamed sites via either active or passive targeting. Polymeric micelles are longer lasting those hydrophobic micelles, exhibiting less CMC or slower dissociation, which allowing for greater drug accumulation. Their virus-like size facilitates improved penetration and retention also referred to in the body. Nanomicelles provide tailored medicine administration by increasing tissue penetration and drug absorption. In polar solvents, regular micelles have an interior that is hydrophobic and a hydrophilic shell, which aids in encapsulating of poorly soluble medicines, increasing their solubility and absorption. Surfactants and block copolymers are used to create nanomicelles, which contain amphiphilic monomers that can be ionic, non-ionic, or zwitterionic. Cationic surfactants included dodecyl trimethyl ammonia bromide, whereas anionic surfactants include sodium dodecyl. This mechanism flow chart in fig 9.Nanomicelles has active targeting capabilities, allowing for maximum delivery while minimizing negative effects. This selectivity stems of their conjugation with targeting moieties, which enables interactions with certain receptors and proteins.³³ Nanomicelles drug delivery used various form of drugs in rheumatoid arthritisit is presented in table 4.

Table 4: Nanomicelles drug delivery used various form in rheumatoid arthritis.

Figure 8: Types of Nanomicelles   Click here to view Figure

Figure 9: Nanomicelles mechanism involved in RA Click here to view Figure

Benefits of nanocarriers in RA therapy

Targeted Delivery: Delivers medicines to inflammatory joints, increasing efficacy.

Controlled Release: Maintains medication levels for extended therapeutic effects.

Reduced Toxicity: Reduces off-target and systemic adverse effects.

Current Trends in Nanotechnology for RA Drug Delivery

Nanotechnology has significantly advanced drug delivery systems for rheumatoid arthritis (RA), offering targeted and efficient therapeutic options. Recent patents highlight innovative approaches in this field and given in Table 5.

Nanocarriers for Conventional Drugs

Improved Delivery of DMARDs

Methotrexate (MTX) and hydroxychloroquine (HCQ) for rheumatoid arthritis. Nanocarriers such as liposomes, polymer nanoparticles, and gold nanoparticles enhance MTX localization to inflamed joints, increasing therapeutic efficacy while reducing systemic toxicity.Lipid-based nanocarriers and polymeric micelles improve HCQ’s cellular absorption, controlled release, and prolonged circulation, leading to superior therapeutic outcomes.

Case studies and preclinical examples

Methotrexate or MTX

Liposomes and Polymeric Nanoparticles

Studies demonstrate that MTX accumulates more in inflamed joints, lowering systemic toxicity and increasing therapeutic results in preclinical RA model.

Gold nanoparticles

MTX-conjugated gold nanoparticles improved joint targeting and decreased inflammation at lower doses. Hydrochloroquine Preclinical investigations showed that lipid-based nanocarriers increased cellular absorption & sustained release with HCQ, hence increasing its efficacy versus synovial inflammation.

Polymeric Micelles

Using animal models of RA, HCQ-loaded micelles demonstrated extended circulation and minimized off-target effects. ⁴³

Nanotechnology for Biological TherapiesDelivery of monoclonal antibodies (e.g., TNF-α inhibitors) and cytokine blockers

Monoclonal antibodies (mAbs) help transport TNF-α inhibitors like infliximab and adalimumab to inflammatory joints, boosting efficacy and minimizing adverse effects.Nanotechnology protects cytokine inhibitors, such as tocilizumab, against degradation, allowing for stable administration.

Strategies to improve efficacy and reduce immunogenicity

Targeted Delivery: Delivers biologics to inflammatory tissues, increasing efficacy and decreasing off-target effects ⁷.Encapsulation protects biologics while improving stability and circulation. Surface modifications reduce immunogenicity & clearance (e.g., PEGylation).

Controlled Release: Provides consistent drug delivery, which improves outcomes, Multifunctional Systems: Combine targeted and protective coatings to improve performance. ⁴⁴

Theranostic Nanoparticles Combining therapeutic and diagnostic capabilities Theranostic nanoparticles combine medication delivery and imaging, allowing for real-time monitoring of illness development and therapy response.

Examples of imaging-guided drug delivery in RA

Magnetic nanoparticles

This are utilized for MRI-guided medication delivery. They aid in the targeting of inflammatory joints while also allowing for real-time monitoring of medication buildup and response to therapy in RA patients.

Fluorescent Nanocarriers

Fluorescence nanoparticles allow optical imaging to track the distribution and release of medications within damaged tissues, providing visible feedback on treatment efficacy.

Radioisotope-Labeled Nanoparticles

Nanoparticles labelled with radioisotopes can be tracked using PET or SPECT imaging  , This enables precise surveillance of the drug’s localization in inflammatory joints and the assessment of inflammation levels. ⁴⁵

Stimuli-Responsive Nanocarriers

pH-Sensitive Nanoparticles

When exposed to the acidic surroundings of RA’s inflamed tissues, these nanoparticles released their therapeutic payload, providing targeted delivery to afflicted areas.

Temperature-Sensitive Nanoparticles

These nanoparticles are designed to release therapeutic content when exposed to the high temperature of inflammatory joints, which improves localized treatment.

Enzyme-Sensitive Nanoparticles

Such nanocarriers deliver medications in reaction to specific enzymes found in the inflammatory synovial environment, allowing for focused and regulated therapy.⁴⁶

Biomimetic and Hybrid Nanoparticles

Biomimetic Nanoparticles

These nanoparticles are made from natural materials such as lipids and proteins, and they imitate biological structures, boosting biocompatibility and immune system interactions, They provide tailored medication administration, minimize toxicity, and improve overall safety in RA therapies.

Hybrid Nanoparticles

These blend synthetic and natural elements to maximize the benefits of both. Hybrid technologies improve drug loading ability, stability, & targeted delivery while retaining biocompatibility, resulting in increased effectiveness in therapy for RA. These trends aim to improve the their biocompatibility safety, and the effectiveness of medication delivery devices in RA. ⁴⁷

Addressing Key Challenges in Nanotechnology for RA

Nanotechnology has the potential to improve RA medication delivery; substantial clinical hurdles remain, such as assuring safety, obtaining precise targeting, and permitting controlled release. Additional challenges, such as manufacturing scalability, regulatory difficulties, patient variation and high costs, necessitate a collaborative effort to make these medicines safe and affordable. Nanomaterials’ biocompatibility or long-term safety are difficult to ensure since they might collect in tissues such as the spleen or liver, generating toxicity concerns. Furthermore, nanomaterials might unintentionally trigger or repress immune responses, thereby exacerbating inflammation, which is very risky for RA patients. It is challenging to precisely target RA-affected tissues, such as inflammatory joints, because even advanced techniques like antibody-linked nanoparticles might generate off-target effects. Furthermore, the fluctuating inflammation in RA makes it difficult for nanocarriers to get to inflamed joints due to fluctuations in vascular permeability. Creating nanoparticles that allow regulated, continuous medication release at target areas is difficult yet necessary for maintaining therapeutic doses and minimizing negative effects. Developing nanocarriers that react to RA-specific cues, like as pH or enzyme shifts, is technically challenging and necessitates careful optimization. Expanding up nanocarrier production while maintaining uniform size, shape, or dosage is difficult since changes can have an impact on treatment efficacy. Furthermore, scaling up nanocarrier production while ensuring consistent size, shape, and dosage is difficult, as variations can affect treatment efficacy. Regulatory approval is particularly challenging, as nanotechnology-based medicines face more rigorous scrutiny than traditional drugs. Importantly, the approval process is area-dependent; different regions (the FDA in the US evaluating them as complex products under NDAs/ANDAs, the EMA in the EU focusing on quality, pharmacokinetics, and bioequivalence, the NMPA in China requiring rigorous preclinical and clinical trials, and the CDSCO in India applying FDA-like guidelines with local bioequivalence standards) have distinct safety, efficacy, and environmental testing requirements, as well as varying standards and manufacturing protocols. This disparity can lead to clinical delays and necessitates significant investment in safety and effectiveness evaluations. Ethical concerns about the long-term effects of persistent nanoparticles on both people and the environment further complicate the landscape. RA patients exhibit diverse disease progressions, immune responses, and drug tolerances, making it hard to develop a one-size-fits-all nanomedicine. Variations in metabolism, immune status, and comorbidities impede personalized therapy efforts. Additionally, nanotechnology-based treatments are often more expensive than conventional therapies, limiting access—especially in low-income regions—while potentially affecting insurance coverage and reimbursement. Various challenges in nanotechnology drug delivery in RA mentioned in fig 10 and its specification in fig 11, fig 12, fig 13, and fig14.

Figure 10: Challenges of nanotechnology in RA Click here to view Figure

Complex Manufacturing and Scalability

Figure 11: Complex Manufacturing & Scalability Challenge. Click here to view figure

High Development Costs

The high costs shown in fig 12 of nanomedicine development and manufacture limit its availability, particularly in low-resource areas, creating a barrier to egalitarian healthcare. Addressing these economic constraints is critical to ensuring nanotechnology’s widespread adoption in clinical practice and the benefits it provides to different patient populations.

Figure 12: High development costs. Click here to view Figure

Potential Toxicity and Immunogenicity

Figure 13: Potential Toxicity and Immunogenicity. Click here to view Figure

Regulatory Hurdles

Nanomedicine regulatory hurdles are caused by continually changing rules, which create uncertainty in approval, standardization, and the commercialization of the product will be governed by the regulatory frameworks of individual countries, ensuring compliance with their specific guidelines and approval processes. Addressing these problems demands the creation of clear, standardized frameworks and RA-specific standards, as well as the harmonization of worldwide regulatory rules to assure uniformity. Building regulatory expertise through training or engagement with specialists can help to speed processes, whereas fostering public-private partnerships promotes collaboration on funding & compliance. Furthermore, using flexible and adaptable approval methods can speed up the approval of nanotechnology in medicine at RA treatment while keeping safety and efficacy criteria.

Variability in Drug Release Kinetics

Figure 14: Variability in drug release kinetics. Click here to view Figure

Integration with Other Therapies (Combining nanotechnology with biologics and other treatment modalities) in RA

It provides a potent strategy for increasing therapy efficacy, improving safety, and enabling more complete disease management. This technique has the potential to improve therapeutic results by enabling for tailored delivery while also decreasing adverse effects. Nanoparticle-based biologic delivery has shown promise, but it is still in the early phases of development, with ongoing research to improve formulations, assess long-term safety, and better understand immune interactions. Advances in “smart” nanoparticles promise to facilitate drug release in reaction to precise triggers to inflamed tissues, resulting in improved control & fewer off-target effects.

Controlled and Sustained Release

Nano carriers enable regulated and prolonged medication release, reducing the need for repeated injections and increasing patient compliance. For example, they may gradually discontinue TNF inhibitors over several weeks, ensuring steady therapeutic doses for better RA therapy.

Combination with Anti-Inflammatory and Disease-Modifying Drugs

Nanotechnology enables the administration of DMARDs such as methotrexate & biologics into a single nanocarrier, boosting their synergistic effects. This focused release at inflammatory areas increases efficacy while lowering systemic toxicity. ⁴⁸

Integration with Gene and RNA Therapies

Nanotechnology enables the administration of gene therapies such as siRNA or CRISPR with biologics, providing an integrated approach to modulating immune responses at the protein & gene levels. This could allow for long-term or permanent management of RA by addressing inflammatory pathways.

Theranostic Approaches (Therapy + Diagnostic)

Theranostic nanocarriers integrate therapy and diagnostics, allowing for simultaneous medication delivery and inflammatory imaging in RA. This enables continuous evaluation & adaptive therapy modifications, which improves illness management.

Immune Modulation with Biologics and Nanocarriers

Nanotechnology improves immune modulation of RA through delivering biologics including immune-modulating molecules via targeted nanocarriers. By targeting the autoimmune fundamental cause, this technique aids in the re-education of immune cells, restoration of tolerance, and the achievement of long-term remission . ⁴⁹

Reducing Immunogenicity of Biologics

By protecting biologics from immune detection, reducing anti-drug antibodies, and improving stability, nanocarriers lessen their immunogenicity. This guarantees sustained effectiveness free from negative immunological responses.

Synergy with Small Molecule Drugs

Biologics for inflammation management & regenerate therapies as growth stimulants for joint healing can be delivered together thanks to nanocarriers. This method treats RA’s tissue regeneration as well as disease control. ⁵⁰

Reducing Dose and Side Effects through Targeted Delivery

Small molecule medications, such as JAK inhibitors, can be co-delivered with biologics thanks to nanotechnology, providing multi-pathway inhibition. This combination improves the management of inflammation, particularly in individuals who are not responding to individual treatments. By delivering treatments straight to inflammatory joints, targeted nanocarriers minimize systemic negative effects and the need for larger dosages. This method guarantees safer and more effective treatment for RA.

Table 5: Examples of various patented Nano technology based drug delivery used RA.

Future Directions and Opportunities

Emerging ideas into RA nanomedicine include the creation smart nanocarriers for personalised medicine that may adapt to unique patient demands by responding of biomarkers and environmental cues, thereby providing tailored therapy. Artificial intelligence and machine learning are used to improve nanoparticle characteristics such as size and surface qualities in order to produce more effective drug delivery devices for RA treatment. Multipurpose nanoparticles are being designed to transport numerous therapeutic drugs that target different RA pathways at the same time, hence enhancing therapy outcomes. The future of patient-specific drug delivery methods involves creating personalised nanocarriers based on particular patient profiles, such as immunological state and disease development, to ensure more accurate and successful therapies. These developing nanomedicine concepts offer major advances in RA treatment by emphasizing personalization, multi-targeted methods, and integrating with cutting-edge technologies. 

Discussion

Nanotechnology provides novel approaches to overcoming the limits of conventional rheumatoid arthritis therapies such as DMARDs and biologics. Nanocarriers are (e.g., nanoparticles, liposomes) allowing precision drug targeting, stimuli-responsive devices for regulated release, & theranostic nanoparticles for integrated therapy and diagnostics are among the most significant advances. New trends, such as personalised medicine, AI-driven optimization, and gene-editing integration, promise better outcomes. However, issues such as optimizing nanoparticle design, assuring long-term safety, and resolving immunogenicity remain. To overcome these challenges, interdisciplinary collaboration will be required to transform nanotechnology-driven systems for drug delivery into effective, patient-specific, & long-term RA treatments. 

Conclusion

Nanotechnology has made major advances in improving rheumatoid arthritis medicine delivery by developing novel solutions such as nanocarriers, theranostic nanoparticles, & stimuli-responsive systems. These developments allow for tailored administration, increased therapeutic efficacy, and lower systemic toxicity, making RA therapy more successful.Emerging advances in RA nanomedicine include personalised therapy, multifunctional nanoparticles, & the incorporation of AI & gene-editing technology. Despite these advancements, problems such as optimizing nanoparticle design, assuring long-term safety, and reducing immunogenicity remain important to the successful use of the nanotechnology in RA therapies. Continuous interdisciplinary collaboration amongst materials scientists, doctors, and pharmacologists is required to overcome these obstacles and improve RA treatment outcomes. Continued study and invention will be critical in developing nanotechnology-driven drug delivery mechanisms treating rheumatoid arthritis, using the ultimate objective of improving patient-specific medicines and obtaining more effective, long-term solutions.

Acknowledgment

Author acknowledges the support to pharmaceutics department, Smbt College of Pharmacy from its management for providing the necessary resources

Funding Sources

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Conflict of Interest

The authors do not have any conflict of interest.

Data Availability Statement

This statement does not apply to this article.

Ethics Statement

This research did not involve human participants, animal subjects, or any material that requires ethical approval.

Informed Consent Statement

This study did not involve human participants, and therefore, informed consent was not required.

Clinical Trial Registration 

This research does not involve any clinical trials.

Permission to reproduce material from other sources

Not Applicable 

Author Contributions

Minal Narkhede: Conceptualization, Supervision, Project Administration.

Shruti Bhamare: Visualization Methodology, Writing – Original Draft, Data Collection, Analysis, Writing – Review &Editing. 

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