Welcome

PLEASE NOTE: From 18 Jan 2010, the news section (see chapter information) will contain a column that will be refreshed weekly. It is based on chapters of an autobiography by NvR. Unfortunately it will be in Dutch only, since much of the linguistic humor, e.g. proverbs used, different meanings of a single word etc. cannot be translated, anyway not by me.
• Please be aware that we do not have any secretarial assistance. As a consequence, an invoice will be sent by email only, twice a year, and for all orders in the past 6 months combined, as far as the total amount is Euro 200 or more. Also, we do not have a VAT number since no tax-paying is required for our non-profit foundation. I do not have the time to fill in specific forms or to provide bank statements or whatsoever. All information is given in the website and in the invoice. The latter is sent to users by email, but can also be printed directly from "My account". If you need a signed form, apart from form W-8BEN (USA), it should be filled in by your institute and sent to me. I will sign everything apart from my death-sentence and I will return it by Fax. Please check before with your financial department whether the above conditions can be met. Otherwise do not order liposomes. You can find a "Pro Forma" invoice under FAQ 22, chapter INFORMATION in our website!!!!

• When ordering liposomes, costs and expected shipping date will automatically appear on the order form when clicking on it. This is to show you this information before sending us the order. Please be aware that this shipping date does apply only to orders of clodronate liposomes and control liposomes that can be taken from the standard batch. Specific requirements, if applicable, may take more time. The suspension of clodronate liposomes should never be frozen, nor be exposed to extreme high temperatures. Store at 4-8 degrees Celcius. If there is a risk that liposomes are stored below zero or at temps over 30 degrees Celsius during transport, do not order liposomes. We cannot control the storage conditions during transport and e.g. in the offices of Customs.

• Fedex tracking numbers can be found under MY ACCOUNT when clicking on ORDERS there. By subsequent clicking on the tracking number you will be connected with the FedEx tracking service to follow your order.

• We anticipate that, before ordering liposomes via this website (see: MY ACCOUNT) and before sending us questions per email, you are known with all information given in our website, especially in the chapters INFORMATION (FAQ inclusive) & COLLABORATION (Costs inclusive).

Liposomes as a tool to manipulate macrophage function

From an evolutionary point of view, macrophages are ancient cells. They form the core of the natural immune system and did appear long before the cells forming together the complex immune system of the higher vertebrates. As a consequence, during the evolution, they did acquire functions both in natural immune reactions and in the regulation of functions of many non-phagocytic cells. The latter functions are mainly mediated by soluble molecules such as cytokines and chemokines.

Macrophages are also involved in "homoiostasis" of the body by ingesting and digesting microorganisms or non-self particles and macromolecules. Digestion is in turn mediated by their lysosomal enzymes.

Liposomes are artificially prepared lipid vesicles, consisting of concentric phospholipid bilayers entrapping aqueous compartments. They can be used to encapsulate strongly hydropihilic molecules solved in aqueous solutions, such as clodronate, a non-toxic bisphosphonate, developed for human application. Freely solved clodronate will not cross liposomal or cellular phospholipid membranes. After injection, liposomes, used as Trojan horses in this case, will be ingested and digested by macrophages followed by intracellular release and accumulation of clodronate. At a certain intracellular concentration, clodronate induces apoptosis of the macrophage. By this approach, i.e. by creating an animal with macrophage depleted tissues or organs, functional aspects of macrophages are studied "in vivo" in many collaborative projects.

Moreover, promising results were obtained by application of clodronate liposomes for suppression of macrophage activity in various models of autoimmune diseases, transplantation, neurological disorders and gene therapy.