Development of a hyperbranched polymer-based methotrexate nanomedicine for rheumatoid arthritis

Marasini, Nirmal; Er, Gerald; Fu, Changkui; Subasic, Christopher; Ibrahim, Jibriil; Skwarczynski, Mariusz; Tóth, István; Whittaker, Andrew K.; Kaminskas, Lisa M.

doi:10.1016/j.actbio.2022.01.054

Cited by 10 publications

(2 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have shown that a single SC dose can achieve a fourfold increase in liver:blood PK AUC ratio compared to the oral TQ equivalent. Recent studies have begun to show the potential of polymer-drug conjugates given by the SC route of administration (76)(77)(78)(79). This work demonstrates that a polymeric prodrug with an enzyme-cleavable linker can function effectively through the SC route.…”

Section: Discussionmentioning

confidence: 88%

Liver-targeted polymeric prodrugs delivered subcutaneously improve tafenoquine therapeutic window for malaria radical cure

Pottenger,

Roy,

Srinivasan

et al. 2024

Sci. Adv.

View full text Add to dashboard Cite

Approximately 3.3 billion people live with the threat of Plasmodium vivax malaria. Infection can result in liver-localized hypnozoites, which when reactivated cause relapsing malaria. This work demonstrates that an enzyme-cleavable polymeric prodrug of tafenoquine addresses key requirements for a mass administration, eradication campaign: excellent subcutaneous bioavailability, complete parasite control after a single dose, improved therapeutic window compared to the parent oral drug, and low cost of goods sold (COGS) at less than $1.50 per dose. Liver targeting and subcutaneous dosing resulted in improved liver:plasma exposure profiles, with increased efficacy and reduced glucose 6-phosphate dehydrogenase–dependent hemotoxicity in validated preclinical models. A COGS and manufacturability analysis demonstrated global scalability, affordability, and the ability to redesign this fully synthetic polymeric prodrug specifically to increase global equity and access. Together, this polymer prodrug platform is a candidate for evaluation in human patients and shows potential for P. vivax eradication campaigns.

show abstract

Section: Discussionmentioning

confidence: 88%

Liver-targeted polymeric prodrugs delivered subcutaneously improve tafenoquine therapeutic window for malaria radical cure

Pottenger,

Roy,

Srinivasan

et al. 2024

Sci. Adv.

View full text Add to dashboard Cite

show abstract

“… 20 Significant advancements have been made in nanoparticle-based strategies for the treatment of inflammation and tumours. Several chronic diseases, such as osteoarthritis, 21 rheumatoid arthritis 22 and skin conditions, 23 have been treated with NSAIDs (non-steroidal anti-inflammatory drugs) or Glucocorticoids as either a primary or adjunctive treatment option. These diseases often require prolonged anti-inflammatory therapy.…”

Section: Introductionmentioning

confidence: 99%

Nanoparticle-Based Drug Delivery Systems for Inflammatory Bowel Disease Treatment

Gao,

Li,

Luo

et al. 2024

DDDT

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is a chronic, non-specific inflammatory condition characterized by recurring inflammation of the intestinal mucosa. However, the existing IBD treatments are ineffective and have serious side effects. The etiology of IBD is multifactorial and encompasses immune, genetic, environmental, dietary, and microbial factors. The nanoparticles (NPs) developed based on specific targeting methodologies exhibit great potential as nanotechnology advances. Nanoparticles are defined as particles between 1 and 100 nm in size. Depending on their size and surface functionality, NPs exhibit different properties. A variety of nanoparticle types have been employed as drug carriers for the treatment of inflammatory bowel disease (IBD), with encouraging outcomes observed in experimental models. They increase the bioavailability of drugs and enable targeted drug delivery, promoting localized treatment and thus enhancing efficacy. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines. Nevertheless, numerous challenges persist in the translation from nanomedicine to clinical application, including enhanced formulations and preparation techniques, enhanced drug safety profiles, and so forth. In the future, it will be necessary for scientists and clinicians to collaborate in order to study disease mechanisms, develop new drug delivery strategies, and screen new nanomedicines.

show abstract

Polymer–drug and polymer–protein conjugated nanocarriers: Design, drug delivery, imaging, therapy, and clinical applications

Guo,

2024

WIREs Nanomed Nanobiotechnol

View full text Add to dashboard Cite

Polymer–drug conjugates and polymer–protein conjugates have been pivotal in the realm of drug delivery systems for over half a century. These polymeric drugs are characterized by the conjugation of therapeutic molecules or functional moieties to polymers, enabling a range of benefits including extended circulation times, targeted delivery, controlled release, and decreased immunogenicity. This review delves into recent advancements and challenges in the clinical translations and preclinical studies of polymer–drug conjugates and polymer–protein conjugates. The design principles and functionalization strategies crucial for the development of these polymeric drugs were explored followed by the review of structural properties and characteristics of various polymer carriers. This review also identifies significant obstacles in the clinical translation of polymer–drug conjugates and provides insights into the directions for their future development.This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

show abstract

Development of a hyperbranched polymer-based methotrexate nanomedicine for rheumatoid arthritis

Cited by 10 publications

References 38 publications

Liver-targeted polymeric prodrugs delivered subcutaneously improve tafenoquine therapeutic window for malaria radical cure

Liver-targeted polymeric prodrugs delivered subcutaneously improve tafenoquine therapeutic window for malaria radical cure

Nanoparticle-Based Drug Delivery Systems for Inflammatory Bowel Disease Treatment

Polymer–drug and polymer–protein conjugated nanocarriers: Design, drug delivery, imaging, therapy, and clinical applications

Contact Info

Product

Resources

About