Formulations

Challenge

A major challenge in the treatment of diseases is the selective transport of active agents to the damaged tissue or organ. Cell membranes are the most important barriers for a targeted drug delivery. Another problem is the degradation or derivatization of free agents in the body which often reduces the specific effect of the drug at the target site. Also, active agents are distributed incorrectly or are changed in the body, which may lead to unwanted side effects. An already-tested way to circumvent these disadvantages is the manufacturing of particulate active ingredient formulations, where the active agent is bound into a polymeric shell or matrix.

Formulation techniques

Particle production techniques and their typical particle sizes.
Particle production techniques and their typical particle sizes. At the Fraunhofer IGB, the technologies outlined in red are established.

At Fraunhofer IGB, customer-specific nano- and microparticles in the range of 200 nm - 10 μm are produced from commercially available or tailor-made polymers, depending on the problem at hand. different polymerization techniques such as miniemulsion polymerization or emulsifier-free emulsion polymerization are used. By varying the particle size, degree of loading, molecular weight and the ratio of hydrophilic and hydrophobic monomer units, we can - individually adapted - influence the release kinetics of the encapsulated substances. Thus, releases over very long periods of time (Ultralong Drug release, ULDr) of three to four months can be realized. Of particular interest here are biodegradable compounds, as these are completely metabolized or decomposed after their application in the body or in the environment.

Tailor-made polymers

Scanning electron microscopic image of biodegradable nanoparticles.
Scanning electron microscopic image of biodegradable nanoparticles. With these particles active substances can be released in the body for a long period of time.

The commercially available biodegradable linear polyesters often have inadequate properties. Therefore, Fraunhofer IGB is developing new polymer matrix systems - biodegradable and biocompatible block copolymers - with improved properties and different molecular weights. The "bioburdened" particles are then adapted to individual applications according to customer requirements and specifications by selecting suitable polymer systems.

Controlled release

Dosing of active ingredients in a traditional and controlled way.
Dosing of active ingredients in the traditional way (above) and in a controlled way (right) with drug delivery systems.

The release kinetics of the active substances from nano- or microparticles is adapted to the respective problem. The various parameters that influence the kinetics are adjusted according to the customer's requirements. In addition, Fraunhofer IGB also generates tailor-made polymers. In particular, the molecular weight and the ratio of hydrophilic and hydrophobic monomer units influence the release kinetics.

Surface modification – Efficient drug targeting

Image of the particle size distribution of microparticles using light microscopy.
Image of the particle size distribution of microparticles using light microscopy.

The polymer nanoparticles can be additionally functionalized on the surface for complex applications. For example, the particles produced at Fraunhofer IGB are modified on their surface via free carboxy groups using conventional coupling methods for the targeted transport of active ingredients in the body (drug targeting). Proteins have already been successfully bound to the nano- and microparticle surface via carbodiimide couplings and other cross-linking chemicals. The design of the particle surface aims to keep the proportion of unspecific binding very low. In addition to biodegradable nano- and microparticles, we are developing biosynthetic nanoparticles that simulate the conditions on cell surfaces (NANOCYTES®).

Reference projects

N2B-patch –

Development of an intranasal form of therapy for the treatment of multiple sclerosis

 

In the EU-funded research project “N2B-patch”, an international consortium is developing an intranasal application platform for biopharmaceutics against diseases of the central nervous system (CNS). Using the treatment of multiple sclerosis as an example, the "Nose2Brain“ approach intends to transport active substances formulated in biomaterials directly through the nose to the brain.

 

Duration: January 2017 – December 2020

Skin Heal – Particle-based formulation for wound healing

 

The particle systems developed here can be applied to a wide variety of problems in the field of formulation of both small-molecule active ingredients and biopharmaceuticals. For example, it has already been possible to encapsulate interferon while fully retaining its bioactivity.

 

 

Cytokine functionalized nanoparticles for cancer therapy – TNF-NANOCYTES®

 

At Fraunhofer IGB, biosynthetic hybrid particles were developed which simulate the conditions on cell surfaces. On the surface of these cell-mimetic nanoparticles mimicking cells, membrane proteins are bound in such a way that their biological properties are fully preserved.

 

 

iP-OSTEO –

Induced pluripotent stem cell seeded active osteochondral nanofibrous scaffolds

 

The iP‑OSTEO project focuses on development of novel cell‑based scaffolds for bone and cartilage repair and will deliver an effective treatment method for patients with poor regenerative capacity. The involved institutions will also help in better integration of academic and industrial stakeholders across Europe as they strengthen the partnerships and promote knowledge transfer across national borders and across different sectors.

 

Duration: February 2019 – January 2023