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

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

Jul 23, 2023 152 likes •282 views

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

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Francesca SELMIN, PhD

MIPOL – Milan Polymer Days February 15-16, 2017

Exploitation of PLGA conjugates in drug delivery

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Implants are…

… non-conventional drug delivery systems for parenteral implantation. Definition (Eur. Pham. 9th 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.

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Implants are…

… non-conventional drug delivery systems whose

performances have to be guaranteed in

terms of

Efficacy Safety Quality

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Critical attributes

  • Biocompatibility
  • Biodegradability
  • Processability
  • Mechanical stability

↓ Loading capacity ↓ Encapsulation efficiency ↓ Chemical stability ↓ Drug release Quality

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Poly(lactide-co-glycolide)

↑Approved ↑Biocompatibility ↑Biodegradability ↑Processability ↑Mechanical stability ↓Limited loading capacity ↓Low encapsulation efficiency ↓Low stability upon sterilization ↓pH decrease

into the -enviroment @ the administration site

2h 7d

Semin Immunol 20 (2008) 86–100

  • J. Control. Rel. 101 (2005) 163–173
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Sterilization of PLGA based DDS and medical devices

Montanari et al. / J Control Rel 56(1998):219-229

H abstraction

Chain scission

In presence of oxygen @ room temperature

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PLGA Anti-oxidant grafted PLGA PLGA conjugates: g-AA-PLGA

AA moiety Polymer DPPH assay (% inhibition) 1h 2h 3h 24h

  • PLGA

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

Anti-oxidant properties

2) AA

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PLGA conjugates: g-AA-PLGA Stability after -sterilization

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 Tg (°C) 42.4±0.5 43.7±0.0 40.7±0.0 41.9±0.2

Cilurzo et al. / PAT 2010(22):2201-2205  g-CA-PLGA  Irradiated g-CA-PLGA

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PLGA conjugates: g-PA-PLGA pH variation during degradation

Cilurzo et al. / PAT 2010(22):2201-2205

PLGA g-PA-PLGA

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PLGA conjugates: g-CA-PLGA In vitro release of a proteic drug

Selmin et al. / J Funct Biomat 2015(6):1-13

EE% D50 (m)  (mV) PLGA

  • 13.80.0
  • 29.81.3

g-CA-PLGA

  • 13.81.1
  • 24.81.4

PLGA 35±0.7 13.10.9

  • 11.23.0

g-CA-PLGA 95.6±2.7 15.41.3

  • 15.11.1
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PLGA conjugates: g-CA-PLGA Stability after -sterilization

Selmin et al. / J Funct Biomat 2015(6):1-13

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

Acknowledgment