Size controlled protein nanoemulsions for active targeting of folate receptor positive cells

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 135; pp. 90 - 98
• Main Authors: Loureiro, Ana, Nogueira, Eugénia, Azoia, Nuno G., Sárria, Marisa P., Abreu, Ana S., Shimanovich, Ulyana, Rollett, Alexandra, Härmark, Johan, Hebert, Hans, Guebitz, Georg, Bernardes, Gonçalo J.L., Preto, Ana, Gomes, Andreia C., Cavaco-Paulo, Artur
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-11-2015
• Subjects: Active control; Active targeting; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Biotecnologia Médica; Cell Line; Chains; Ciências Médicas; Copolymers; Drug Delivery Systems; Emulsions; Folate Receptors, GPI-Anchored - drug effects; Folic acid; Folic Acid - metabolism; High pressure homogenization; Homogenizing; Humans; Medicin och hälsovetenskap; Nanoemulsions; Nanoparticles; Nanostructure; Particle Size; PEGylated surfactant; Poloxamer; Polyethylene glycol; Polyethylene Glycols; Polymers; Propylene Glycols; Protein-based nanoemulsions; Proteins - chemistry; Proteins - pharmacology; Receptors; Science & Technology; Serum Albumin, Bovine - chemistry; High pressure homogenization; PEGylated surfactant; Active targeting; Protein-based nanoemulsions; Folic acid
• ISSN: 0927-7765; 1873-4367; 1873-4367; 0927-7765
• DOI: 10.1016/j.colsurfb.2015.06.073

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•Stable BSA nanoemulsions are produced by high pressure homogenization.•Linear correlation is found between Poloxamer 407 levels and size of nanoemulsions.•Presence of BSA-FA conjugate results in specific FA mediated internalization in folate receptor positive cells.
Bovine serum albumin (BSA) nanoemulsions were produced by high pressure homogenization with a tri-block copolymer (Poloxamer 407), which presents a central hydrophobic chain of polyoxypropylene (PPO) and two identical lateral hydrophilic chains of polyethylene glycol (PEG). We observed a linear correlation between tri-block copolymer concentration and size – the use of 5mg/mL of Poloxamer 407 yields nanoemulsions smaller than 100nm. Molecular dynamics and fluorescent tagging of the tri-block copolymer highlight their mechanistic role on the size of emulsions. This novel method enables the fabrication of highly stable albumin emulsions in the nano-size range, highly desirable for controlled drug delivery. Folic Acid (FA)-tagged protein nanoemulsions were shown to promote specific folate receptor (FR)-mediated targeting in FR positive cells. The novel strategy presented here enables the construction of size controlled, functionalized protein-based nanoemulsions with excellent characteristics for active targeting in cancer therapy.