Exploitation of PLGA conjugates in drug delivery Francesca SELMIN, - PowerPoint PPT Presentation

Exploitation of PLGA conjugates in drug delivery Francesca SELMIN, PhD MIPOL – Milan Polymer Days February 15-16, 2017

Implants are… … non -conventional drug delivery systems for parenteral implantation. Definition (Eur. Pham. 9 th ed 2017) … sterile, solid preparations of a size and shape suitable for parenteral implantation and release of the active substance(s) over an extended period of time. Each dose is provided in a sterile container.

Implants are… … non -conventional drug delivery systems whose performances have to be guaranteed in terms of Quality Safety Efficacy

Critical attributes Quality • ↓ Loading capacity Biocompatibility • ↓ Encapsulation efficiency Biodegradability • ↓ Chemical stability Processability • ↓ Drug release Mechanical stability

Poly(lactide-co-glycolide) ↑ Approved ↓ Limited loading capacity ↑ Biocompatibility ↓ Low encapsulation efficiency ↑ Biodegradability ↓ Low stability upon sterilization ↑ Processability ↑ Mechanical stability ↓ pH decrease into the  -enviroment 2h 7d @ the administration site Semin Immunol 20 (2008) 86 – 100 J. Control. Rel. 101 (2005) 163 – 173

Sterilization of PLGA based DDS and medical devices H abstraction In presence of oxygen @ room temperature Chain scission Montanari et al. / J Control Rel 56(1998):219-229

Anti-oxidant properties PLGA conjugates: g-AA-PLGA 2) AA PLGA Anti-oxidant grafted PLGA DPPH assay (% inhibition) AA moiety Polymer 1h 2h 3h 24h -- PLGA 0 0 0 0 Pyrogallic acid g-PA-PLGA 76 77 81 98 Caffeic acid g-CA-PLGA 92 93 93 98 Resveratrol g-RV-PLGA 27 32 37 56

Stability after  -sterilization PLGA conjugates: g-AA-PLGA Before irradiation After irradiation PLGA g-PA-PLGA PLGA g-PA-PLGA Mn (kDa) 12.1±0.0 9.2±0.1 8.9±0.3 9.2±0.2 Mw (kDa) 17.3±2.9 16.3±0.1 15.2±0.2 15.9±0.2 PI 1.4±0.2 1.8±0.1 1.8±0.01 1.6±0.02 T g (°C) 42.4±0.5 43.7±0.0 40.7±0.0 41.9±0.2  g-CA-PLGA  Irradiated g-CA-PLGA Cilurzo et al. / PAT 2010(22):2201-2205

pH variation during degradation PLGA conjugates: g-PA-PLGA PLGA g-PA-PLGA Cilurzo et al. / PAT 2010(22):2201-2205

In vitro release of a proteic drug PLGA conjugates: g-CA-PLGA D 50 (  m)  EE% (mV) 13.8  0.0 -29.8  1.3 PLGA - 13.8  1.1 -24.8  1.4 g-CA-PLGA - 13.1  0.9 -11.2  3.0 PLGA 35±0.7 15.4  1.3 -15.1  1.1 g-CA-PLGA 95.6±2.7 Selmin et al. / J Funct Biomat 2015(6):1-13

Stability after  -sterilization PLGA conjugates: g-CA-PLGA Selmin et al. / J Funct Biomat 2015(6):1-13

Acknowledgment @DisFarm - UniMI Francesco CILURZO Paola MINGHETTI Giulia MAGRI Luisa MONTANARI @DisFEB - UniMI Stefano BELLOSTA Silvia CASTIGLIONI @uniCAL Francesco PUOCI