Despite recent advances in the treatment of rheumatoid arthritis(RA) attributed to biologic medications, only a minority of patients achieve andmaintain disease remission without the need for continuous immunosuppressive therapy.1Complicating the treatment of RA further is the development of tolerance over timeor failure of patients to respond to currently available therapies.1Thus, the development of new treatment strategies for RA remains a priority.
Nanotherapies for RA have received increasing attention in the past decade because they offer several potential advantages compared with conventional systemic therapies.2 Nanocarriers are submicron transport particles designed to deliver the drug at the site of inflammation the synovium thereby maximizing its therapeutic effect and avoiding unwanted systemic adverse effects.1 This targeted drug delivery approach also has the potential to minimize the amount of drug required to control joint inflammation3 and increase local bioavailability by protecting it from degradation in the circulation.1
In essence, nanotechnology enables the redesign of alreadyeffective rheumatologic medications into nanoformulations that may confer greaterspecificity, longer therapeutic effect, and more amenable safety profile.4Nanoencapsulated nonsteroidal anti-inflammatory drugs (NSAIDs),5 liposomaland polymeric preparations of glucocorticoids,6 and nanosystems thatdirectly inhibit angiogenesis are just several examples of nanotherapies that havebeen tested in experimental models of inflammatory arthritis.7
Despite the promising findings observed in studies to date, further development and subsequent integration of nanotherapies in the management of RA remains hampered by the lack of efficacy and toxicity studies in humans. In an interview with Rheumatology Advisor, Christine Pham, MD, chief of the Division of Rheumatology at the Washington University School of Medicine in St Louis, discussed the advantages and challenges of applying nanotherapies in RA.
RheumatologyAdvisor: How can nanotechnology be applied in the treatment of RA?
ChristinePham, MD: Nanotechnology is a multidisciplinary approach aimed at the deliveryof therapeutic agents using submicron nanocarriers. In RA, the vessels at the siteof inflammation are leaky, allowing passage of these nanocarriers from the circulationto specific target sites in the joint environment.
RheumatologyAdvisor: Which RA drugs are suitable forthis approach?
DrPham: Many conventionalantirheumatic drugs such as methotrexate, glucocorticoids, and NSAIDs have beensuccessfully delivered by nanocarriers to mitigate inflammatory arthritis in experimentalmodels.
RheumatologyAdvisor: Whatare the main advantages of using nanotherapy/nanocarriers, as opposed to systemictherapy, in the treatment of RA?
DrPham: The mainadvantages are selective drug delivery to desired sites of action through passiveor active targeting, which can lead to increased local bioavailability and potentiallycan reduce unwanted off-target side effects. In addition, nanocarriers may increasethe solubility of certain drugs and protect therapeutics against degradation inthe circulation.
RheumatologyAdvisor: Howfar has the medical community gotten in developing (and testing) nanotherapies forRA? Which nanotherapies have shown the most promise?
DrPham: A numberof nanotherapeutics have been developed and tested in animal models of RA. Mosthave shown disease mitigation, however, none has so far made it to the clinic.
RheumatologyAdvisor: Whatneeds to happen before nanotherapies can get fully integrated into clinical practiceand treatment of patients with RA?
DrPham: Insufficientdata regarding long-term toxicity and optimal therapeutic efficacy have hamperedtheir integration into clinical practice. Anticytokine biologics have been verysuccessful, so nanotherapeutics need to show clearly that they have higher efficacyand lower toxicity for pharmaceutical companies to invest in their development forthe clinic.
Rheumatology Advisor: Are any other promising treatment strategies for RA currently under investigation?
DrPham: RNA interference(RNAi) has recently emerged as a specific way to silence gene expression. The invivo delivery of small interfering RNA (siRNA), however, remains a significant hurdle,given the short half-life of the molecule in the circulation. We have used a self-assemblingpeptide-based nanosystem that protects the siRNA from degradation when injectedintravenously and which has shown to mitigate experimental RA.8,9 siRNAworks by knocking down NFkappaB p65, asubunit of NF-kappa-B transcription complex which plays acentral role in inflammation in general and in RA in particular. This platform promisesto have real translational potential.
References
1. Pham CTN. Nanotherapeutic approaches for the treatment of rheumatoid arthritis. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2011;3(6):607-619.
2. Dolati S, Sadreddini S, Rostamzadek D, Ahmadi M, Jadidi-Niaragh F, Yousefi M. Utilization of nanoparticle technology in rheumatoid arthritis treatment. Biomed Pharmacother. 2016;80:30-41.
3. Rubinstein I, Weinberg GL. Nanomedicine for chronic non-infectious arthritis: the clinicians perspective. Nanomedicine. 2012;8(Suppl 1):S77-S82.
4. Henderson CS, Madison AC, Shah A. Size matters nanotechnology and therapeutics in rheumatology and immunology. Curr Rheumatol Rev. 2014;10(1):11-21.
5. Srinath P, Chary MG, Vyas SP, Diwan PV. Long-circulating liposomes of indomethacin in arthritic ratsa biodisposition study. Pharm Acta Helv. 2000;74:399-404.
6. Metselaar JM, Wauben MH, Wagenaar-Hilbers JP, Boerman OC, Storm G. Complete remission of experimental arthritis by joint targeting of glucocorticoids with long-circulating liposomes. Arthritis Rheum. 2003;48:2059-2066.
7. Koo OM, Rubinstein I, nyuksel H. Actively targeted low-dose camptothecin as a safe, long-acting, disease-modifying nanomedicine for rheumatoid arthritis. Pharm Res. 2011;28:776-787.
8. Zhou H-F, Yan H, Pan H, et al. Peptide-siRNA nanocomplexes targeting the NF-kB subunit p65 suppress nascent experimental arthritis. J Clin Invest. 2014;124:4363-4374.
9. Rai MF, Pan H, Yan H, Sandell L, Pham C, Wickline SA. Applications of RNA interference in the treatment of arthritis. Transl Res. 2019;214:1-16.
Go here to see the original:
- Is there an alternative to radiation - November 8th, 2009 [November 8th, 2009]
- Taiwan exploring how nanotech affects health - November 8th, 2009 [November 8th, 2009]
- A new way of treating cancer on the way? - November 8th, 2009 [November 8th, 2009]
- Lasers can destroy cancer cells - November 8th, 2009 [November 8th, 2009]
- Fluorescent molecules can be biomarkers - November 8th, 2009 [November 8th, 2009]
- Quick blood tests by using a nanodevice - November 8th, 2009 [November 8th, 2009]
- Where will medicine be 20 years from now - November 8th, 2009 [November 8th, 2009]
- History of nanotechnology - November 8th, 2009 [November 8th, 2009]
- Nanotech and Cancer - November 8th, 2009 [November 8th, 2009]
- Nanotechnology in medicine - November 8th, 2009 [November 8th, 2009]
- How does cancer start - January 25th, 2010 [January 25th, 2010]
- Lung cancer symptoms - January 26th, 2010 [January 26th, 2010]
- Signs of breast cancer - January 27th, 2010 [January 27th, 2010]
- Famous people with cancer - January 29th, 2010 [January 29th, 2010]
- Metastatic renal cancer - January 30th, 2010 [January 30th, 2010]
- What causes skin cancer - January 31st, 2010 [January 31st, 2010]
- How many people die from cancer each year - February 1st, 2010 [February 1st, 2010]
- How much money is spent on cancer research - February 2nd, 2010 [February 2nd, 2010]
- Colon cancer warning signs - February 4th, 2010 [February 4th, 2010]
- Prostate cancer symptoms - February 4th, 2010 [February 4th, 2010]
- Nano-devices that cross blood-brain barrier open door to treatment of cerebral palsy - April 25th, 2012 [April 25th, 2012]
- Nano-devices that cross blood-brain barrier open door to treatment of cerebral palsy, other neurologic disorders - April 25th, 2012 [April 25th, 2012]
- Nanomaterial properties in complement activation: lessons from nanomedicine - Video - May 4th, 2012 [May 4th, 2012]
- OMICS Group :: International Conference and Exhibition on Nanotechnology - May 4th, 2012 [May 4th, 2012]
- Use of Nanotechnology in Medicine [FOX 11-27-2011] - Video - May 4th, 2012 [May 4th, 2012]
- Cancer Nanomedicine - Detection - Video - May 4th, 2012 [May 4th, 2012]
- Cancer Nanomedicine - Video - May 4th, 2012 [May 4th, 2012]
- HBIO Reports First Quarter 2012 Revenue Growth of 8% Over First Quarter 2011 - May 5th, 2012 [May 5th, 2012]
- Nano science, focus of Education Ministry - May 7th, 2012 [May 7th, 2012]
- Drug-resistant Bacteria - Designing Nanoparticles For High Antibiotic Doses - May 7th, 2012 [May 7th, 2012]
- Research and Markets: Global Market for Nano Silver - May 10th, 2012 [May 10th, 2012]
- Cracking study makes nanotech breakthrough - May 10th, 2012 [May 10th, 2012]
- Nanoparticles may pose environmental threat - May 16th, 2012 [May 16th, 2012]
- Global Nanobiotechnology Industry - May 17th, 2012 [May 17th, 2012]
- 'Inability to give back Singur land my biggest regret' - May 20th, 2012 [May 20th, 2012]
- 'KOREA PACK 2012' for Packing process industry to be held at KINTEX - May 23rd, 2012 [May 23rd, 2012]
- New ISO Technical Report Guides Characterization of Nanomaterials in Toxicology - May 29th, 2012 [May 29th, 2012]
- DNA strands create tiniest Smileys - May 30th, 2012 [May 30th, 2012]
- Health and fitness agenda: Evolution Asia Yoga Conference - June 2nd, 2012 [June 2nd, 2012]
- UC Davis work in humanities receives $150,000 in UC-wide grants - June 2nd, 2012 [June 2nd, 2012]
- Computer-designed proteins 'may help fight variety of flu viruses' - June 3rd, 2012 [June 3rd, 2012]
- 'Nano technology' [program can pay off big for IRSC students - June 3rd, 2012 [June 3rd, 2012]
- Computer-designed proteins programmed to disarm variety of flu viruses - June 3rd, 2012 [June 3rd, 2012]
- Jugaad innovators don't plan - they improvise - June 6th, 2012 [June 6th, 2012]
- Health and fitness agenda: World Blood Donor Day - June 9th, 2012 [June 9th, 2012]
- OMICS Group :: Journal of Nanomedicine - June 9th, 2012 [June 9th, 2012]
- Researchers develop a 'time bomb' to fight cardiovascular disease - June 10th, 2012 [June 10th, 2012]
- Nanotechnologists develop a 'time bomb' to fight cardiovascular disease - June 10th, 2012 [June 10th, 2012]
- 'Time bomb' to fight cardiovascular disease developed - June 11th, 2012 [June 11th, 2012]
- Asia's First Graphene Nano-Tech Facility Opens In Singapore - June 13th, 2012 [June 13th, 2012]
- How worms are pioneering remote control medicine - June 13th, 2012 [June 13th, 2012]
- Golden Helix Establishes Direct Presence in Japan - June 13th, 2012 [June 13th, 2012]
- STDs Blocked by Nano Gel, Study Suggests - June 15th, 2012 [June 15th, 2012]
- Real Products, Different Results - June 15th, 2012 [June 15th, 2012]
- The Puridone Program - A Breakthrough for Painkiller Addiction - June 15th, 2012 [June 15th, 2012]
- Six startup medical device firms compete in Memphis for fame and fortune - June 19th, 2012 [June 19th, 2012]
- International Nanomedicine Conference bound for Sydney: July 2-4, 2012 - June 19th, 2012 [June 19th, 2012]
- Taming light with graphene - June 21st, 2012 [June 21st, 2012]
- Today on New Scientist: 25 June 2012 - June 26th, 2012 [June 26th, 2012]
- A step towards the future - July 1st, 2012 [July 1st, 2012]
- Genia Technologies Collaborates with Professors Jingyue Ju at Columbia and George Church at Harvard to Develop a ... - October 4th, 2012 [October 4th, 2012]
- Scientists Invited To Submit Proposals For Biological Research In Space - October 4th, 2012 [October 4th, 2012]
- Research and Markets: Micro-Nano Technology XIII from the 13th Annual Conference of Chinese Society of Micro-Nano ... - October 6th, 2012 [October 6th, 2012]
- $80M research facility to open at UMass Lowell - October 6th, 2012 [October 6th, 2012]
- Nano-revolution in drugs delivery - October 8th, 2012 [October 8th, 2012]
- SENAI/SESI of Sao Paulo Selects NanoProfessor as Foundation for "Nanomundo" Nanotechnology Education Initiative - October 8th, 2012 [October 8th, 2012]
- Delivering an integral approach to emotional and mental health - October 9th, 2012 [October 9th, 2012]
- NanoGuardian's On-Dose NanoEncryption Brand Protection Technology to Be Presented at AAPS Annual Meeting - October 11th, 2012 [October 11th, 2012]
- Il Nano Mondo del professor Ennio Tasciotti - Video - October 30th, 2012 [October 30th, 2012]
- Deakin University - Practical Science - Nano medicine - Video - October 30th, 2012 [October 30th, 2012]
- 2012 Deakin University 3 Minute Thesis Finalist - Jarrad Altimari - Video - October 30th, 2012 [October 30th, 2012]
- Nano Medicine from "Development of Nanotechnology in Hong Kong" - Video - October 30th, 2012 [October 30th, 2012]
- NANO Medicine 1 3 xvid - Video - October 30th, 2012 [October 30th, 2012]
- Nanolääke // Nano medicine - Video - October 30th, 2012 [October 30th, 2012]
- NANO Medicine (1-3) - Video - October 30th, 2012 [October 30th, 2012]
- Jefferson County, Colorado's Bioscience Industry - Video - October 30th, 2012 [October 30th, 2012]
- NanoMission - Nanomedicine NanoBot - Video - October 30th, 2012 [October 30th, 2012]
- Study aims to unlock mysteries of autism - November 20th, 2012 [November 20th, 2012]
- Catherine Griwkowsky - November 22nd, 2012 [November 22nd, 2012]
- Kulkarni to be feted at Bangalore Nano 2012 - November 26th, 2012 [November 26th, 2012]