(674j) Improved Entrapment of N-Acetyl Cysteine (NAC) in Nanoparticles of Poly[Lactic-Co-Glycolic Acid] (PLGA) Prepared By Double Emulsion Method By Using Bovine Serum Albumin (BSA)

NAC is a drug with many actual and potential applications as a result of its antioxidant properties [1]. However, low oral bioavailability (4 to 10 %) and its strong hydrophilic character allowing easy excretion by renal pathway, impose limits to systemic concentration of NAC and, therefore, to therapeutic activity  [2]. Encapsulation and slow release of NAC from a polymeric matrix could extend both residence time and time-averaged concentration in the body.

The double emulsion method has been used to entrap hydrophilic compounds within hydrophobic polymeric matrices such as PLGA; however, the resulting capture efficiency of the drug tends to be extremely low. The use of BSA has been reported to improve entrapment efficiency  [3].  The general purpose of this study was to evaluate the use of BSA as a medium to improve the encapsulation efficiency of NAC in nanoparticles of PLGA made by the double emulsion method.

Methodology:

PLGA and a surfactant were dissolved into Dichloromethane (DCM). An aqueous solution of BSA and NAC was then emulsified into the DCM/surfactant/PLGA solution by ultrasound. The resultant emulsion was subsequently emulsified into an aqueous solution of Pluronic F127 by ultrasound.  After DCM evaporation, PLGA nanoparticles containing NAC were formed and characterized by particle size, zeta potential, drug efficiency entrapment and drug release kinetics. The effect of PLGA and surfactant concentrations in DCM in the first emulsion, of BSA and NAC concentrations on water in the first emulsion, and of organic/aqueous phase ratio in the second emulsion on particle characteristics was assessed. 

Results:

BSA improves the entrapment efficiency of NAC in nanoparticles of PLGA. Concentration of polymer in DCM or NAC in water affect both entrapment efficiency and particle size.  The presence of a surfactant is important in order to stabilize the first emulsion.

Overall, for best conditions evaluated, nanoparticles showed a particle size between 200 and 350 nm and entrapment efficiency around 8%. In vitro drug release studies showed a burst release within the first hour, followed by a reduction in the release rate.  

Conclusion:

Results suggest that bovine serum albumin improves retention of hydrophilic compounds like N-Acetylcysteine into hydrophobic polymeric matrices such as PLGA. 

References:

[1]         M. Zafarullah, W. Q. Li, J. Sylvester, and M. Ahmad, “Cellular and Molecular Life Sciences Molecular mechanisms of N -acetylcysteine actions,” C. Cell. Mol. Life Sci., vol. 60, pp. 6–20, 2003.

[2]         K. Suzuki, “Anti-oxidants for therapeutic use: why are only a few drugs in clinical use?,” Adv. Drug Deliv. Rev., vol. 61, no. 4, pp. 287–9, Apr. 2009.

[3]         D. Chitkara and N. Kumar, “BSA-PLGA-Based Core-Shell Nanoparticles as Carrier System for Water-Soluble Drugs.,” Pharm. Res., no. 12, Jun. 2013.