cmRNA/lipoplex encapsulation in PLGA microspheres enables transfection via calcium phosphate cement (CPC)/PLGA composites.
In this study lipoplexes containing chemically modified messenger RNA (cmRNA) were incorporated into poly (lactic-co-glycolic acid) (PLGA) microspheres via water-in-oil-in-water (W/O/W) double emulsion solvent evaporation technique. The nanoparticle encapsulation by microparticle formation was optimized to achieve lipoplex release and maximum transfection efficiency in surrounding cells. It was possible to adjust characteristic features in surface topology and size of the PLGA-microspheres by varying the extent of lipoplex loading into the polymer matrix. The partial release of lipids and mRNA out of the microparticle system, their accumulation in cells and the production of encoded protein were visualized via fluorescence microscopy. These bioactive microspheres, containing cmRNA bearing lipoplexes, were developed for the incorporation of a therapeutic component into injectable calcium phosphate cements (CPC). Due to the incorporation of PLGA/lipoplex microspheres as a degradable entity, the porosity of the cement phase could additionally be adjusted. This approach of complex nanoparticle incorporation into polymer/cement composites represents a promising example for combining transcript therapy with biomechanical engineering.
Ludwig-Maximilians-Universität München, Department of Pharmacy, Germany.
Maximilian
M
Utzinger
Ludwig-Maximilians-Universität München, Department of Pharmacy, Germany.
Anita
A
Jarzebinska
ethris GmbH, Germany.
Nicolas
N
Haag
ethris GmbH, Germany.
Martin
M
Schweizer
Ludwig-Maximilians-Universität München, Department of Pharmacy, Germany.
Gerhard
G
Winter
ethris GmbH, Germany.
Christian
C
Dohmen
ethris GmbH, Germany.
Carsten
C
Rudolph
Technische Universität München, Institute of Molecular Immunology & Experimental Oncology, Germany. Electronic address: christian.plank@tum.de.
Christian
C
Plank
D000818:Animals; D002130:Calcium Phosphates / Q000737:chemistry*; D002460:Cell Line; D019344:Lactic Acid / Q000737:chemistry*; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D011100:Polyglycolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D012333:RNA, Messenger / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D014162:Transfection / Q000379:methods*
D002130:Calcium Phosphates; D012333:RNA, Messenger; C523618:calcium phosphate polylactic-co-glycolic acid composite; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid
Bone substitute materials; Calcium phosphate cements; Lipoplexes; Microparticles; PLGA; Transcript therapy