Peptide-grafted nanogels for sustained endothelin and bradykinin blockade in osteoarthritis.

Osteoarthritis (OA) is a widespread cause of physical disability and chronic pain, yet it lacks a pharmacological cure due to the difficulty of delivering drugs to avascular cartilage. We recently developed peptide-grafted nanogels for intra-articular injection that were well tolerated in vivo in healthy equine joints. Hence, this study reports the pharmaceutical aspects of this drug delivery system, which is based on biopolymeric nanohydrogels (nanogels, NG) for the localized, sustained delivery of two peptide antagonists of endothelin-1 (ETA) and bradykinin (BKB1), namely BQ123 and R954.

Growth differentiation factor 5 improves meniscal healing in a pilot study on rats.

Purpose: Meniscus injuries are common, but failed repairs remain an issue. The aim of this study was to demonstrate, in an in vivo rat model, the ability of growth differentiation factor 5 (GDF5) to improve meniscal tear healing.

Methods: Eight Lewis rats (four females and four males) underwent radial tear of the medial meniscus on the right knee.

Evidence from a mouse model supports repurposing an anti-asthmatic drug, bambuterol, against Alzheimer's disease by administration through an intranasal route.

Bambuterol is a long-acting anti-asthmatic prodrug which releases terbutaline. Terbutaline is an agonist of the β-adrenergic receptors which is formed by decarbamoylation of bambuterol by butyrylcholinesterase. Inhibition of the latter, as well as activation of β-AR, are of interest for the treatment of Alzheimer's disease (AD).

Bioinspired Bottlebrush Polymers Effectively Alleviate Frictional Damage Both In Vitro and In Vivo.

Bottlebrush polymers (BB) have emerged as compelling candidates for biosystems to face tribological challenges, including friction and wear. This study provides a comprehensive assessment of an engineered triblock BB polymer's affinity, cell toxicity, lubrication, and wear protection in both in vitro and in vivo settings, focusing on applications for conditions like osteoarthritis and dry eye syndrome. Results show that the designed polymer rapidly adheres to various surfaces (e.

In vitro evaluation of NA1-115-7-loaded nanoemulsions, an MCL-1-specific inhibitor of natural origin, intended to treat B-cell lymphoproliferative disorders after oral administration.

MCL-1, an anti-apoptotic member of the BCL-2 protein family, is overexpressed in many types of cancer and contributes to chemotherapy resistance. The drimane derivative NA1-115-7 is a natural compound isolated from Zygogynum pancheri that can be considered as a very promising lead for treating MCL-1-dependent hematological malignancies. As this drug suffers from low stability in acidic conditions and poor aqueous solubility, we evaluated the potential oral use of NA1-115-7 by encapsulating it in lipid nanoemulsions (NA-NEs) prepared by spontaneous emulsification.

NA1-115-7, from Zygogynum pancheri, is a new selective MCL-1 inhibitor inducing the apoptosis of hematological cancer cells but non-toxic to normal blood cells or cardiomyocytes.

The overexpression of antiapoptotic members (BCL-2, BCL-xL, MCL-1, etc.) of the BCL-2 family contributes to tumor development and resistance to chemotherapy or radiotherapy. Synthetic inhibitors targeting these proteins have been developed, and some hematological malignancies are now widely treated with a BCL-2 inhibitor (venetoclax).

How nano-engineered delivery systems can help marketed and repurposed drugs in Alzheimer's disease treatment?

Given the continual increase in the number of patients and the lack of curative treatment, the development of new therapies to treat Alzheimer's disease (AD) is becoming ever more urgent. In this review, we summarize the most promising preclinical studies in, and the significant benefits offered by, nanocarriers to realize the full potential of marketed drugs and identify repurposed drugs. No clinical trials have yet been conducted on nanocarriers for drug repurposing in AD.

Active Targeted Nanoemulsions for Repurposing of Tegaserod in Alzheimer's Disease Treatment.

Background And Purpose: The activation of 5-HT receptors with agonists has emerged as a valuable therapeutic strategy to treat Alzheimer's disease (AD) by enhancing the nonamyloidogenic pathway. Here, the potential therapeutic effects of tegaserod, an effective agent for irritable bowel syndrome, were assessed for AD treatment. To envisage its efficient repurposing, tegaserod-loaded nanoemulsions were developed and functionalized by a blood-brain barrier shuttle peptide.

Drimane Derivatives as the First Examples of Covalent BH3 Mimetics that Target MCL-1.

Drimane sesquiterpenoid dialdehydes are natural compounds with antiproliferative properties. Nevertheless, their mode of action has not yet been discovered. Herein, we demonstrate that various drimanes are potent inhibitors of MCL-1 and BCL-xL, two proteins of the BCL-2 family that are overexpressed in various cancers, including lymphoid malignancies.

Design of Non-Haemolytic Nanoemulsions for Intravenous Administration of Hydrophobic APIs.

Among advanced formulation strategies, nanoemulsions are considered useful drug-delivery systems allowing to improve the solubility and the bioavailability of lipophilic drugs. To select safe excipients for nanoemulsion formulation and to discard any haemolytic potential, an in vitro miniaturized test was performed on human whole blood. From haemolysis results obtained on eighteen of the most commonly used excipients, a medium chain triglyceride, a surfactant, and a solubilizer were selected for formulation assays.

8-Alkynyl-3-nitroimidazopyridines display potent antitrypanosomal activity against both T. b. brucei and cruzi.

An antikinetoplastid pharmacomodulation study was done at position 8 of a previously identified pharmacophore in 3-nitroimidazo[1,2-a]pyridine series. Twenty original derivatives bearing an alkynyl moiety were synthesized via a Sonogashira cross-coupling reaction and tested in vitro, highlighting 3 potent (40 nM ≤ EC blood stream form≤ 70 nM) and selective (500 ≤ SI ≤ 1800) anti-T. brucei brucei molecules (19, 21 and 22), in comparison with four reference drugs.