Berunda polypeptides: Bi-headed rapamycin carriers for subcutaneous treatment of autoimmune dry eye disease.

08:00 EDT 16th May 2019 | BioPortfolio

Summary of "Berunda polypeptides: Bi-headed rapamycin carriers for subcutaneous treatment of autoimmune dry eye disease."

The USFDA-approved immunosuppressive drug Rapamycin (Rapa), despite its potency, is limited by poor bioavailability and a narrow therapeutic index. In this study, we sought to improve bioavailability of Rapa under subcutaneous (SC) administration and to test its therapeutic feasibility and practicality towards Sjögren's Syndrome (SS), which is a systemic autoimmune disease and has no approved therapies. To improve its therapeutic index, we formulated Rapa with a carrier termed FAF, a fusion of the human cytosolic FK506-binding protein 12 (FKBP12) and an Elastin-like polypeptide (ELP). The resulting 97 kDa
i) has minimal burst release; ii) is 'humanized'; iii) is biodegradable; iv) solubilizes two Rapa per FAF; and v) avoids organic solvents or amphiphilic carriers. Demonstrating high stability, FAF remained soluble and monodisperse with a hydrodynamic radius of 8 nm at physiological temperature. A complete pharmacokinetic (PK) analysis of FAF revealed that the bioavailability of subcutaneous (SC) FAF was 60% with increased the mean residence time (MRT) up to 20.3 hrs compared to 10.7 hrs for IV administration. After 24 hrs injection, the plasma concentration of Rapa delivered by FAF was 8 times higher with significantly increased plasma-to-whole blood ratio relative to free Rapa. To evaluate therapeutic effects, FAF-Rapa was administered SC every other day for 2-weeks to non-obese diabetic (NOD) mice that develop lacrimal gland (LG) inflammation with mechanisms comparable to Sjögren's Syndrome (SS). Both FAF-Rapa and free Rapa exhibited immunomodulatory effects by significantly suppressing lymphocytic infiltration, gene expressions of IFN-γ, MHC II, type I collagen and IL-12a, and cathepsin S (CTSS) activity in the LG compared to controls. Serum chemistry and histopathological analyses in major organs revealed no apparent toxicity of FAF-Rapa. Given its improved PK and equipotent therapeutic efficacy compared to free Rapa, FAF-Rapa may be of further interest for systemic treatments for autoimmune diseases like SS.


Journal Details

This article was published in the following journal.

Name: Molecular pharmaceutics
ISSN: 1543-8392


DeepDyve research library

PubMed Articles [18953 Associated PubMed Articles listed on BioPortfolio]

Rapamycin relieves inflammation of experimental autoimmune encephalomyelitis by altering the balance of Treg/Th17 in a mouse model.

This study was to observed the different doses of rapamycin on the treatment of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. 63 female C57BL/6 mice (6-8 weeks) was chosen and rando...

Research advances of autoimmune liver diseases in 2018.

Autoimmune liver disease is a group of hepatobiliary injuries mediated by abnormal immunity. It mainly includes autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis. Re...

Next generation strategies for geroprotection via mTORC1 inhibition.

Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) with the pharmaceutical rapamycin prolongs the lifespan and healthspan of model organisms including rodents, with evidence now emerging...

Rapamycin regulates cholesterol biosynthesis and cytoplasmic ribosomal proteins in hippocampus and temporal lobe of APP/PS1 mouse.

As an inhibitor of the immune system and a longevity drug, rapamycin has been suggested as a treatment for Alzheimer's disease, although the underlying mechanisms remain to be clarified. To elucidate ...

Early Switch to Mammalian Target of Rapamycin Inhibitors Is a Sustainable Treatment Approach in Renal Transplant Recipients: 7-Year Results.

The aim of this study was to investigate the safety and sustainability of mammalian target of rapamycin inhibitor (m-TORi)-based treatment protocols in renal transplant patients.

Clinical Trials [3184 Associated Clinical Trials listed on BioPortfolio]

Efficacy of Rapamycin in the Treatment of Cervico-facial Lymphatic Malformations

To evaluate the efficacy of Rapamycin in extended cervicofacial lymphatic malformations in pediatric patients. Rapamycin is administered oral for a 6 month period. The success rate is det...

Rapamycin+Estradiol- vs. Rapamycin-Eluting Stents to Reduce Restenosis (ISAR-PEACE)

The purpose of this study is to evaluate whether adding estradiol to rapamycin better prevents coronary artery reblockage after drug-eluting stent implantation.

Rapamycin in Relapsed Acute Lymphoblastic Leukemia

This is a research study designed to look at the biological effects of two drugs on leukemia cells. In this study, we are comparing the effects of drugs called corticosteroids when used a...

Adjuvant Anti-Recurrence Treatment With Rapamycin on Early-stage HCC

To evaluate the clinical effect of rapamycin combined with TACE on early-stage HCC with overexpression of ASPH after radical surgery using randomized controlled study and provide a new ant...

Pre Transplant Rapamycin Treatment in Islet Transplantation Alone

Numerous changes to the original Edmonton protocol have been proposed in the attempt of improving the still unsatisfactory long-term function of ITA. Rapamycin may blunt the early inflamma...

Medical and Biotech [MESH] Definitions

Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.


A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that TACROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.

A household that includes children and is headed by one adult.

The uptake of substances via the SUBCUTANEOUS TISSUE.

Quick Search


DeepDyve research library

Relevant Topics

Autoimmune Disorders
Autoimmune disorders are conditions that occurs when the immune system mistakenly attacks and destroys healthy body tissue. There are more than 80 different types of autoimmune disorders. Normally the immune system's white blood cells help protect ...

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Searches Linking to this Article