Title : Radiolabeled drug/ligand loaded Micelles: Exploring diagnostic and therapeutic potentials for glioma through the intranasal route
Abstract:
Developing effective methods for drug delivery into the brain is one of the major challenges faced today. In the current arena the research fraternity is mostly involved in the drug discovery and chemical modification of pre-existing molecules which certainly do not facilitate enhanced uptake for most of the systemically administered chemotherapeutic agents. The reason being the complex structure of the blood brain barrier (BBB).
Malignant gliomas are the most common primary tumors that occur in the human brain. The 5-year survival rate for patients with glioblastoma is less than 5% even with surgery followed by radiation and chemotherapy. According to the recent reports, brain cancer is on the rise in geriatric population, also, there are disturbing reports of the brain tumor in younger age groups. Currently, on the diagnosis front, invasive biopsy is the preferred method to confirm the diagnosis of cancer. Some modern brain imaging techniques such as PET, PET-CT, SPECT and SPECT-CT are the various modalities for the detection of tumors and cancers, however, the delivery of contrast/imaging agents when given systematically as an aid for brain imaging is inefficient, due to the complex structure of BBB. On the therapy front, standard treatment consists of maximal surgical resection, radiotherapy, and concomitant and adjuvant chemotherapy with Temozolomide or other anti-cancer drugs either given orally, intrathecally or through the convection enhanced delivery (through skull). Thus, harnessing the potential advantage of BBB bypassing non-invasive route for preferential delivery of diagnostic and therapeutic agents to glioma becomes the prime requirement in the current arena.
Previous studies undertaken in our lab (Jain et. al., 2010) have proved the potential of drug loaded micellar nanocarriers for higher brain uptake through the olfactory axonal pathway. Keeping this in mind we further developed safe, stable, economic and industrially feasible micellar nanocarriers for diagnostic and therapeutic usage to be delivered using non-invasive intranasal route. In order to explore the diagnostic and therapeutic potentials, we radiolabeled the chemotherapeutic drug Methotrexate and the targeting ligand Folic acid with 99mTc (Technetium) using the Design of Experiments approach. The radiolabeled moieties were found to be stable upon evaluation under various nasal and cerebrospinal fluid mimicked conditions. Further, the same were encapsulated into micelles for intranasal administration. The radiolabeled drug loaded micelles were also found to be stable when evaluated under nasal and cerebrospinal fluid mimicked conditions.
Audience take away:
- The fabrication of micellar nano-carrier systems
- Radiolabeling of Drugs and Ligands
- Use of diagnostic and therapeutic potentials of nanocarriers and radionuclides
- These insights could further be used by the audience to explore the area of specific targeting of drug/diagnostic agent with the aid of nano formulations.
