Recent advances in medicinal chemistry and pharmaceutical technology--strategies for drug delivery to the brain.
This paper provides a mini-review of some recent approaches for the treatment of brain pathologies examining both medicinal chemistry and pharmaceutical technology contributions. Medicinal chemistry-based strategies are essentially aimed at the chemical modification of low molecular weight drugs in order to increase their lipophilicity or the design of appropriate prodrugs, although this review will focus primarily on the use of prodrugs and not analog development. Recently, interest has been focused on the design and evaluation of prodrugs that are capable of exploiting one or more of the various endogenous transport systems at the level of the blood brain barrier (BBB). The technological strategies are essentially non-invasive methods of drug delivery to malignancies of the central nervous system (CNS) and are based on the use of nanosystems (colloidal carriers) such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, polymeric micelles and dendrimers. The biodistribution of these nanocarriers can be manipulated by modifying their surface physico-chemical properties or by coating them with surfactants and polyethylene-glycols (PEGs). Liposomes, surfactant coated polymeric nanoparticles, and solid lipid nanoparticles are promising systems for delivery of drugs to tumors of the CNS. This mini-review discusses issues concerning the scope and limitations of both the medicinal chemistry and technological approaches. Based on the current findings, it can be concluded that crossing of the BBB and drug delivery to CNS is extremely complex and requires a multidisciplinary approach such as a close collaboration and common efforts among researchers of several scientific areas, particularly medicinal chemists, biologists and pharmaceutical technologists.
Denora
Nunzio
N
Dipartimento Farmaco-Chimico, Facoltà di Farmacia, Università degli Studi di Bari, Via Orabona 4, 70125 Bari, Italy.
Trapani
Adriana
A
Laquintana
Valentino
V
Lopedota
Angela
A
Trapani
Giuseppe
G
D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002491:Central Nervous System Agents / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical / Q000639:trends; D050091:Dendrimers / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000639:trends*
D002491:Central Nervous System Agents; D050091:Dendrimers; D004337:Drug Carriers; D008081:Liposomes; D008823:Micelles