Comparative study of doxorubicin-loaded poly(lactide-co-glycolide) nanoparticles prepared by single and double emulsion methods

• Published in: European journal of pharmaceutics and biopharmaceutics 2007-06, Vol.66 (3), p.488-492
• Main Authors: Tewes, F., Munnier, E., Antoon, B., Ngaboni Okassa, L., Cohen-Jonathan, S., Marchais, H., Douziech-Eyrolles, L., Soucé, M., Dubois, P., Chourpa, I.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Chemistry, Pharmaceutical; Double emulsion; Doxorubicin; Doxorubicin - administration & dosage; Doxorubicin - chemistry; Emulsions; General pharmacology; Lactic Acid - administration & dosage; Life Sciences; Medical sciences; Microbiology and Parasitology; Nanoparticles; Partition coefficient; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; PLGA nanoparticles; Polyglycolic Acid - administration & dosage; Polymers - administration & dosage; Release kinetics; Single emulsion; Solubility; Technology, Pharmaceutical - methods
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2007.02.016

This study describes how the control of doxorubicin (DOX) polarity allows to encapsulate it inside poly(lactide-co-glycolide) (PLGA) nanoparticles formulated either by a single oil-in-water (O/W) or a double water-in-oil-in-water (W/O/W) emulsification method (SE and DE, respectively). DOX is commercially available as a water soluble hydrochloride salt, which is useful for DE. The main difficulty related to DE approach is that the low affinity of hydrophilic drugs to the polymer limits entrapment efficiency. Compared to DE method, SE protocol is easier and should provide an additional gain in entrapment efficiency. To be encapsulated by SE technique, DOX should be used in a more lipophilic molecular form. We evaluated the lipophilicity of DOX in terms of apparent partition coefficient ( P) and modulated it by adjusting the pH of the aqueous phase. The highest P values were obtained at pH ranging from 8.6 to 9, i. e. between two DOX p K a values (8.2 and 9.6). The conditions favorable for the drug lipophilicity were then used to formulate DOX-loaded PLGA nanoparticles by SE method. DOX encapsulation efficiency as well as release profiles were evaluated for these nanoparticles and compared to those with nanoparticles formulated by DE. Our results indicate that the encapsulation of DOX in nanoparticles formulated by SE provides an increased drug entrapment efficiency and decreases the burst effect.