Improving the therapeutic window of anticancer agents by β-cyclodextrin encapsulation: Experimental and theoretical insights

drug delivery, Today's cyclodextrin, ,

Today’s cyclodextrin is about the stabilization effect of CDs on proteins, yet from a different angle.

I shared a lot earlier about the potential of CDs replacing surface active agents, yet how about combining them?

This study from Roquette led by Rajeev Gokhale and Vinod T. investigates the collaborative impact of combining polysorbates and HPβCD as excipients in protein formulations. The introduction of HPβCD in formulations showed it considerably reduced aggregation in two model proteins, bevacizumab and ipilimumab, following exposure to various stress conditions. The diffusion interaction parameter revealed a reduction in protein-protein interactions by HPβCD.

The study suggests that combining these excipients can improve mAb stability in formulations, offering an alternative for the biopharmaceutical industry.

Improving the therapeutic window of anticancer agents by β-cyclodextrin encapsulation: Experimental and theoretical insights – ScienceDirect

mAb, monoclonal antibodies, carbohyde

Pharmaceutical composition and application patent

Today's cyclodextrin, ,

Today’s cyclodextrin is an interesting application proposed by RemeGen Biosciences, which uses methyl-BCD to remarkably improve the pharmaceutical effect of antibody-drug conjugates. By using CDs, the ACD load can be lower, thus greatly reducing the production cost and the treatment cost of a patient.
If you are interested in similar solutions, check out Formulation development – www.carbohydesolutions.com

Espacenet – Pharmaceutical composition and application thereof

Smaller size packs a stronger punch – Recent advances in small antibody fragments targeting tumour-associated carbohydrate antigens

carbohydrates,

Very educative review on recent advances in small antibody fragments targeting tumor-associated carbohydrate antigens
Glycans represent the most versatile post-translational modification in nature and surround all human cells. Unique glycan structures are monitored by the immune system and differentiate self from non-self and healthy from malignant cells. Aberrant glycosylations, termed tumor-associated carbohydrate antigens (TACAs), are a hallmark of cancer and are correlated with all aspects of cancer biology. Therefore, TACAs represent attractive targets for monoclonal antibodies for cancer diagnosis and therapy. However, due to the thick and dense glycocalyx as well as the tumor micro-environment, conventional antibodies often suffer from restricted access and limited effectiveness in vivo. To overcome this issue, many small antibody fragments have come forth, showing similar affinity with better efficiency than their full-length counterparts. In this paper, small antibody fragments against specific glycans on tumour cells and highlighting their advantages over conventional antibodies are presented.
Sana Khan Khilji, Charlotte Op ‘t Hoog, David Warschkau, Felix Goerdeler, Anika Freitag, Peter Seeberger, Oren Moscovitz

See the article here

Lilly drug slows Alzheimer’s by 35%, bolstering treatment approach

carbohydrates, drug development, , ,

Lilly’s Alzheimer’s drug donanemab slows cognitive decline by 35% in PhIII
An experimental Alzheimer’s drug developed by Eli Lilly and Company slowed cognitive decline by 35% in a late-stage trial, providing what experts say is the strongest evidence yet that removing sticky amyloid plaques from the brain benefits patients with the fatal disease.
Lilly’s drug, donanemab, met all goals of the trial: It slowed the progression of Alzheimer’s by 35% compared to a placebo in 1,182 people with an early-stage disease whose brains had deposits of two key Alzheimer’s proteins, beta-amyloid as well as intermediate levels of tau, a protein linked with disease progression and brain cell death.

See the article on reuters.com: Lilly drug slows Alzheimer’s by 35%, bolstering treatment approach

Method for Reduced Aggregate Formation in Downstream Processing of Bispecific Antigen-Binding Molecules

Today's cyclodextrin, ,

This is a great example of using CDs in a downstream processing method to produce bispecific antigen-binding molecule. In Amgen‘s invention, β-CD is applied in the process either in a buffer applied in the filtration step or added to the filtration pool after the UF/DF filtration step to keep the product in a non-aggregated form.
Yan Wang; Nicholas Marchand; Robert Brake; Maria Perry; Ashish Sharma; Eugene Sun

See the full patent here.

Incorporation of Hydrophilic Macrocycles Into Drug-Linker Reagents Produces Antibody-Drug Conjugates With Enhanced in vivo Performance

Today's cyclodextrin, ,

Antibody-drug conjugates (ADCs) have begun to fulfill their promise as targeted cancer therapeutics with ten clinical approvals to date. Recently the role that linker-payload reagent design has on the properties of ADCs has been highlighted as an important consideration for developers. In this paper from Abzena, the effect of incorporating hydrophilic macrocycles like cyclodextrin into reagent structures on the in vitro and in vivo behavior of ADCs.

Nick Evans, Ruslan Grygorash, Nicolas Camper, Mark Frigerio, Matthew Bird et al

See the full article here

Methyl-BCD is used in antibody-drug conjugate

Today's cyclodextrin, ,

An interesting application is highlighted in the patent of RemeGen荣昌生物: methyl-BCD is used in antibody-drug conjugate formulations where the primary benefit is that ADC dose can be lowered (due to higher efficacy), which leads to mitigating safety concerns lowering costs, and patient treatment costs. Fascinating, huh? (Figure: Araris Biotech AG)

See the full patent on Espacenet.