title: Poly ɛ-caprolactone nanoparticles loaded with Uncaria tomentosa extract: preparation, characterization, and optimization using the Box-Behnken design.
abstract: OBJECTIVE
  The aim of this research was to develop and optimize a process for obtaining poly ɛ-caprolactone (PCL) nanoparticles loaded with Uncaria tomentosa (UT) extract.
  
  
  METHODS
  Nanoparticles were produced by the oil-in-water emulsion solvent evaporation method. Preliminary experiments determined the initial conditions of the organic phase (OP) and of the aqueous phase (AP) that would be utilized for this study. Ultimately, a three-factor three-level Box-Behnken design (BBD) was employed during the optimization process. PCL and polyvinyl alcohol (PVA) concentrations (X(1) and X(2), respectively) and the AP/OP volume ratio (X(3)) were the independent variables studied, while entrapment efficiency (Y(1)), particle mean diameter (Y(2)), polydispersity (Y(3)), and zeta potential (Y(4)) served as the evaluated responses.
  
  
  RESULTS
  PRELIMINARY EXPERIMENTS REVEALED THAT THE OPTIMAL INITIAL CONDITIONS FOR THE PREPARATION OF NANOPARTICLES WERE AS FOLLOWS: OP composed of 5 mL ethyl acetate/acetone (3/2) mixture containing UT extract and PCL, and an AP of buffered PVA (pH 7.5) solution. Statistical analysis of the BBD results indicated that all of the studied factors had significant effects on the responses Y(1), Y(2), and Y(4,) and these effects are closely described or fitted by regression equations. Based on the obtained models and the selected desirability function, the nanoparticles were optimized to maximize Y(1) and minimize Y(2). These optimal conditions were achieved using 3% (w/v) PCL, 1% (w/v) PVA, and an AP/OP ratio of 1.7, with predicted values of 89.1% for Y(1) and 280 nm for Y(2). Another batch was produced under the same optimal conditions. The entrapment efficiency of this new batch was measured at 81.6% (Y(1)) and the particles had a mean size of 247 nm (Y(2)) and a polydispersity index of 0.062 (Y(3)).
  
  
  CONCLUSIONS
  This investigation obtained UT-loaded nanoparticle formulations with desired characteristics. The BBD approach was a useful tool for nanoparticle development and optimization, and thus should be useful especially in the realm of phytotherapeutics, in which varied compositions may be assessed in quantitative and qualitative terms.
authors: Department of Pharmaceutics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
authors: Ana Ferreira
authors: AF
authors: Ribeiro
authors: Ricardo Leite
authors: RL
authors: de Oliveira Rezende
authors: Lúcio Mendes
authors: LM
authors: Cabral
authors: Valéria Pereira
authors: VP
authors: de Sousa
mesh_terms: D000704:Analysis of Variance; D020948:Cat's Claw / Q000737:chemistry*; D055598:Chemical Phenomena; D006863:Hydrogen-Ion Concentration; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010936:Plant Extracts / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D012044:Regression Analysis; D012107:Research Design
chemical_list: D010936:Plant Extracts; D011091:Polyesters; C016240:polycaprolactone
keywords: PCL; anti-tumorigenic; cat’s claw; design of experiments; nanochemoprevention
references: Colloids Surf B Biointerfaces. 2010 Jan 1;75(1):1-18
references: 19782542
references: Int J Nanomedicine. 2011;6:3429-41
references: 22267927
references: Int J Pharm. 2007 Mar 1;331(2):153-9
references: 17157461
references: Int J Pharm. 2007 Mar 6;332(1-2):55-63
references: 17169518
references: Int J Nanomedicine. 2009;4:321-33
references: 20054435
references: Int J Pharm. 2008 Feb 28;350(1-2):320-9
references: 17913411
references: Adv Drug Deliv Rev. 2008 Dec 14;60(15):1615-26
references: 18840489
references: Int J Pharm. 2010 Jan 29;385(1-2):113-42
references: 19825408
references: J Ethnopharmacol. 2010 Jul 6;130(1):127-33
references: 20435132
references: J Control Release. 1999 Feb 1;57(2):171-85
references: 9971898
references: Cancers (Basel). 2011 Oct 26;3(4):4024-45
references: 24213123
references: Biochem Pharmacol. 2010 Jun 1;79(11):1640-7
references: 20105430
references: Phytochemistry. 2005 Jan;66(1):5-29
references: 15649507
references: Int J Nanomedicine. 2012;7:3951-9
references: 22866004
references: Int J Pharm. 2010 Apr 15;389(1-2):186-94
references: 20038446
references: Int J Pharm. 2011 Nov 25;420(1):122-32
references: 21864661
references: Int J Pharm. 2009 Dec 1;382(1-2):277-90
references: 19703530
references: Eur J Pharm Biopharm. 2008 Mar;68(3):513-25
references: 17983737
references: Eur J Pharm Biopharm. 2008 May;69(1):1-9
references: 17826969
references: Phytochem Anal. 2012 Mar-Apr;23(2):143-51
references: 21809407
references: Int J Nanomedicine. 2012;7:4391-408
references: 22927757
references: Int J Nanomedicine. 2012;7:3961-9
references: 22888239
references: Phytomedicine. 2007 Apr;14(4):280-4
references: 17296291
references: Int J Nanomedicine. 2011;6:683-92
references: 21556343
references: Int J Pharm. 2011 Jan 17;403(1-2):201-6
references: 20951783
references: Pharm Res. 2009 May;26(5):1025-58
references: 19107579
references: Int J Nanomedicine. 2012;7:2975-86
references: 22787393
references: J Biomed Mater Res A. 2009 Sep 15;90(4):1128-36
references: 18671265
references: Int J Nanomedicine. 2012;7:4311-21
references: 22915852
references: Planta Med. 2010 Feb;76(2):133-6
references: 19724995
references: Int J Pharm. 2005 Feb 16;290(1-2):137-44
references: 15664139
references: Pharmacol Rep. 2007 Sep-Oct;59(5):565-72
references: 18048957
references: Food Chem Toxicol. 2007 Nov;45(11):2206-18
references: 17619071
references: Eur J Pharm Biopharm. 2009 Sep;73(1):25-33
references: 19508892
references: Int J Nanomedicine. 2012;7:4089-98
references: 22888245