The addition of polyethylene glycol (PEG) on the surface of liposomes increases their circulation time when administered intravenously. However, the inclusion of PEG using PEGylated phospholipids could result in a possible micelles formation. The development of chimeric systems mixing synthetic biocompatible and biodegradable PEG-containing copolymers with lipids is a strategy to obtain as well PEGylated liposomes. Microfluidics is an innovative manufacturing technology easy to scale up that presents high reproducibility, low batch-to-batch variation, and better control over particles characteristics. Taking advantage of this technique, in this research work, chimeric stealth liposomes were produced mixing five different synthesized methoxy-poly(ethylene glycol)-block-poly(δ-decalactone) (mPEG-PDL, varying in polymer length) with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol. The obtained chimeric formulations were around 150 nm in size with a narrow distribution and an almost neutral surface charge. Ovalbumin (OVA) was used as a model protein to evaluate the loading potential reaching an encapsulation efficiency of 41±4 %. The prepared systems showed no cytotoxicity in vitro on THP-1 cell with an uptake up to 89±4 % after 3 h. Finally, protein integrity after encapsulation was confirmed with DQ-OVA. In this work, we demonstrated that using microfluidics, it is possible to produce stable and highly protein-loaded chimeric stealth liposomes with good physicochemical characteristics, no toxicity, protein integrity, and effective uptake by endocytosis.

Microfluidic production of protein loaded chimeric stealth liposomes

Tiboni, Mattia;Casettari, Luca
2020-01-01

Abstract

The addition of polyethylene glycol (PEG) on the surface of liposomes increases their circulation time when administered intravenously. However, the inclusion of PEG using PEGylated phospholipids could result in a possible micelles formation. The development of chimeric systems mixing synthetic biocompatible and biodegradable PEG-containing copolymers with lipids is a strategy to obtain as well PEGylated liposomes. Microfluidics is an innovative manufacturing technology easy to scale up that presents high reproducibility, low batch-to-batch variation, and better control over particles characteristics. Taking advantage of this technique, in this research work, chimeric stealth liposomes were produced mixing five different synthesized methoxy-poly(ethylene glycol)-block-poly(δ-decalactone) (mPEG-PDL, varying in polymer length) with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol. The obtained chimeric formulations were around 150 nm in size with a narrow distribution and an almost neutral surface charge. Ovalbumin (OVA) was used as a model protein to evaluate the loading potential reaching an encapsulation efficiency of 41±4 %. The prepared systems showed no cytotoxicity in vitro on THP-1 cell with an uptake up to 89±4 % after 3 h. Finally, protein integrity after encapsulation was confirmed with DQ-OVA. In this work, we demonstrated that using microfluidics, it is possible to produce stable and highly protein-loaded chimeric stealth liposomes with good physicochemical characteristics, no toxicity, protein integrity, and effective uptake by endocytosis.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11576/2679933
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 10
social impact