CapsInject™
Capsulution technology for in vivo prolonged release of biologicals from LBL coatings
Background
Biologics such as peptides and proteins often require special injectable formulations for optimal performance, providing either protection against too fast degradation by body enzymes, or to provide a controlled release for prolonging the action, or both.
The Capsulution Approach: CapsInject™
A simple approach for prolonged release over hours or days is the coating of biologicals with the layer-by-layer (LBL) technology. Oppositely charged polymers are layered alternately on each other.
- Fig. 1: Coating of a crystal of a biological molecule by LBL (left) or inclusion of molecules in between the layers (right, composition of layers on template)
The in vivo proof – insulin as model
In this proof of concept study insulin was used as a model protein, and encapsulated by a different number of layers as described in Fig. 1. The first layer was each time dextransulfate, followed by protaminesulfate, dextransulfate and so on.
From in vitro release profiles it is very difficult to estimate the actual real release time in vivo. Therefore to assess the effect of different numbers of layers, the formulations were tested in vivo. As most relevant, ultimate performance criterion the in vivo effect was taken.
In vivo prolonged release
During the first 5 hours the glucose level of the rats injected with NaCl solution stayed between 80 and 100%.
Injection of insulin in acetate buffer (Ins AB) distinctly reduced the glucose levels to a minimum at about 3 hours, followed by a steady increase just below the control NaCl group at 8 hours (Fig. 2).
The formulation with 4 coating layers (F4) showed a less pronounced decrease during the first 3 hours, which can be explained by the prolonged release of lower concentrations of insulin. Then a minimum of 20% of the initial glucose concentration is reached and this low level remains until 8 hours due to the ongoing prolonged release of insulin.
- Fig. 2: Glycaemia in % of initial value over 8 hours after s.c. injection of NaCl solution, insulin in buffer (Ins AB) and the LBL the formulation F4 with 4 coating layers.
With CapsInject™...
- Protection against too fast degradation by body enzymes
- controlled release for prolonging the action
Contact
Michaela Grabo, Senior Research Scientist New Technologies
Capsulution Pharma AG, Volmerstr. 7b, 12489 Berlin, Germany
Mail: m.grabo@capsulution.com
Tel.: +49 (0)30-670 69 19 0
Fax: +49 (0)30-670 69 19 101
www.capsulution.com