BBB-Therapeutics B.V.

Drug delivery to the brain remains challenging due to the presence of the blood-brain barrier. In this review, 10 key development criteria are presented that are important for successful drug development to treat CNS diseases by targeted drug delivery systems. Although several routes of delivery are being investigated, such as intranasal delivery, direct injections into the brain or CSF, and transient opening of the blood-brain barrier, the focus of this review is on physiological strategies aiming to target endogenous transport mechanisms. Examples from literature, focusing on targeted drug delivery systems that are being commercially developed, will be discussed to illustrate the 10 key development criteria. The first four criteria apply to the targeting of the blood-brain barrier: (1) a proven inherently safe receptor biology, (2) a safe and human applicable ligand, (3) receptor specific binding, and (4) applicable for acute and chronic indications. Next to an efficient and safe targeting strategy, as captured in key criteria 1 to 4, a favorable pharmacokinetic profile is also important (key criterion 5). With regard to the drug carriers, two criteria are important: (6) no modification of active ingredient and (7) able to carry various classes of molecules. The final three criteria apply to the development of a drug from lab to clinic: (8) low costs and straightforward manufacturing, (9) activity in all animal models, and (10) strong intellectual property (IP) protection. Adhering to these 10 key development criteria will allow for a successful brain drug development.

A review.The central nervous system (CNS) is one of the most difficult organs to reach when it comes to the treatment of brain-related illnesses.This unmet medical market is very large as it affects 2 billion people worldwide - a number that is expected to grow with increasing life expectancy and an expanding global population (1).Although most drugs currently in development against neurol. targets show high efficacy for their target, they often cannot reach the brain in sufficient amounts to exert an effect due to presence of the neuroprotective blood-brain barrier.This results in cessation of their development due to, for example, dose-limiting toxicity outside the CNS or off-target effects.This includes approx. 98% of the small mols. and nearly all of the large biotechnol. drugs, such as recombinant proteins or gene-based medicines (2).