Author + information
- Prakash Sojitra1,
- Saami Yazdani2,
- Fumiyuki Otsuka2,
- Manish Doshi1,
- Frank Kolodgie2 and
- Renu Virmani2
Objective of this study was to develop non-polymeric sirolimus nanoparticle coated balloon and demonstrate in-tissue transfer through DCB in rabbit model.
Drug coated balloon (DCB) is an emerging technology. To date paclitaxel is a choice in DCB. Due to lipophilic properties of sirolimus, short time delivery through DCB is a major challenge. To overcome current limitations, we hypothesized; nanoparticle sirolimus coated on the balloon can provide better delivery and retention.
We prepared phospholipid encapsulated sirolimus and coated on the balloon with novel coating formulation. The characteristics of the nanoparticle sirolimus DCB was tested in both an in-vitro and preclinical in-vivo models. New Zealand rabbits underwent drug coated balloon dilatation in iliac arteries for pharmacokinetics, confocal microscopy and scanning electronic microscopy studies.
Sirolimus nanoparticles were ∼400nm with stable solution. Coating surface was smooth without defect and irregularities. In-tissue uptake of sirolimus was at 1, 7 and 14 days with concentration of 140.6, 15.5 and 5.5 ng/mg, respectively. Sirolimus coated balloon with 3x inflations was also safe in the rabbit iliac arteries. Confocal microscopy showed homogeneous fluorescent tagged nano sirolimus (DTF-nSRL) distribution into the artery wall with intima to adventitia flow. None of the in-vivo investigation has reflected emboli in downward stream.
Present set of experiments showed adequate amount of sirolimus was delivered through non-polymeric DCB. Multiple inflation demonstrated safety to co-relate with actual clinical outcome. Confocal imaging has showed homogenous distribution in cross section and longitude parts. Path of drug travel was to the deepen area of arterial wall upon time from intima to adventitia (Table 1).
- 2013 American College of Cardiology Foundation