Development of nanoparticles with ‘improved drug loading’ for local delivery to the brain in the treatment of medulloblastoma

Abstract

Poor CNS penetration by cancer drugs limits their application in sensitive brain tumours such as medulloblastoma. An alternative approach, delivering drugs directly to residual tumour using nano particulate delivery systems (NPDS) could reduce some of these problems. The main challenges hindering the clinical translation of the use of NPDS for local delivery of drugs to the residual tumour are inadequate drug loading and erratic release. This study focusses on understanding the conditions required for the development of a NPDS with sufficient drug loading for post-surgical delivery to the residual tumour. This was done by selecting known effective drugs; Etoposide, etoposidephosphate and teniposide and matching them with modified poly (glycerol) adipate based polymers based on the interactions observed between them. Fourier transform infra-red spectroscopy (FTIR), contact angle measurements and drug release experiments have been used to screen the drugs and substituted PGA based polymers. Based on the interactions observed, polymers were matched with the specific drugs. Two types of drug nanoparticles were prepared from these combinations. Drug loaded matrix polymer nanoparticles (NP) were prepared by an interfacial deposition method and a novel process of applying a polymer coating to drug nanoparticles, polymer coated drug nanoparticles (PCDNP) was also developed. The following drug loading results were obtained for etoposide (NP:5%, PCDNP: 77%) and teniposide (NP: 23%, PCDNP: 32%). This systematic approach to monitor drug and polymer interactions to match polymers to drugs resulted in the formulation of nanoparticles with higher drug loading. Keywords: Medulloblastoma, Nanoparticles, Etoposide, Etoposide phosphate, Teniposide, Poly(glycerol)-adipate