Tissue specific delivery by harnessing the targeting ability of albumin
Systemic delivery of drugs gives rise to several challenges, such as uniform biodistribution and inadequate specificity to diseased tissue. Traditionally, this has been compensated by administrating a large total dose to achieve high local concentration, which unfortunately may result in non-specific toxicity and other adverse effects.
The effectiveness of active pharmaceutical compounds greatly increases when these are delivered directly to their site of action. To attain site specific delivery, various drug targeting platforms have been developed over the years. Albumin stands out due to its intrinsic ability to accumulate in specific disease tissue.
Inflamed tissue and tumor accumulation using recombinant albumin
Tumor accumulation by albumin:
Albumin’s propensity for tumor accumulation has been well demonstrated. Exposing growing tumors to color- or radioactive labelled albumin demonstrates how albumin specifically targets various tumor tissue. Read more on this here
Several reasons for this specific tumor targeting of albumin have been reported:
- It has been observed that serum albumin levels deplete in cancer patients, suggesting that albumin is taken up as a food source by the tumors. Read more here
- The ability of albumin to accumulate in tumors is furthermore attributed to passive targeting in areas with leaky vasculature, the so-called Enhanced Permeability Effect. Learn more here
- Engagement of albumin with cellular receptors, such as SPARC, Gp60 and Gp30, have been hypothesized to enhance tumor uptake through a receptor mediated mechanism. Learn more here
Although the exact reasons for albumin’s ability to accumulate in tumors have not been clarified, a number of albumin–cytotoxin constructs have been shown to be suitable for tumor delivery, with the most prominent being Celgene’s Abraxane®, approved by the FDA for use against advanced breast, pancreatic and non-small cell lung cancer.
Inflamed tissue accumulation by albumin:
Following similar mechanisms for the targeting ability of albumin against tumors, site specific targeting by albumin against inflamed tissue has been demonstrated using a collagen induced arthritis model. Read more here
The prospect of using albumin as a carrier for targeting active pharmaceutical compounds to diseased tissue has been achieved by the fusion of an interleukine-1 receptor antagonist to albumin. Read more here
Enhanced drug targeting at diseased tissue using Veltis® technology platform
When using albumin as a drug targeting platform, our recombinant human albumin Recombumin® and its drug delivery technology Veltis® holds many advantages over plasma derived human serum albumin (HSA), both in terms of its performance, versatility, safety and controllability. When employing Albumedix’ technologies it is therefore possible to target tumors and/or inflamed tissues by albumin site-specific delivery of one or more drugs for increased potency or bispecificity.