Statistical analysis of low molecular mass heparin nanoencapsulation.
The objective of this study was to use Box-Behnken design (BBD) to investigate the influence of formulation variables on the properties of heparin-loaded poly(lactic-coglycolic acid) (PLGA)-polymethacrylate-RLPO (E-RLPO) nanoparticles (NP) in terms of mean diameter (as size) and drug encapsulation efficiency. The NPs were prepared by the double emulsion solvent evaporation method. The independent variables were: X1 - polymer mass ratio (PLGA:E-RLPO) in the oil phase, X2 - concentration of polyvinyl alcohol (PVA) as emulsion stabilizer, and X3 - volume of the external aqueous phase (W2). Particle size (analyzed by dynamic light scattering) and encapsulation efficiency (EE, estimated by spectrophotometry) were the investigated responses. The polynomial equation obtained from regression analysis of the reduced model (p = 0.0002, F = 25.7952 and R2 = 0.96) provided an excellent fit. The optimal size for the NP was found to be 134.2 ± 16.5 nm with formulation variables of 48.2:61.8, 0.321 (%,m/V) and 263 mL for X1, X2 and X3, respectively. Probably, due to electrostatic interaction between the negatively charged drug and the positively charged E-RLPO, the percent EE of heparin was between 74.4 ± 6.5 % (lowest value) and 92.1 ± 5.3 % (highest value). The data suggest that BBD is a useful tool in rational design of heparin-loaded NPs.
Laboratory of Future Nanomedicines and Theoretical Chronopharmaceutics, University of Missouri-Kansas City, School of Pharmacy, Division of Pharmaceutical Sciences, Kansas City, MO 64108, USA.
Vaishnavi
V
Ganti
Abebe Endale
AE
Mengesha
Jacob
J
Marszalek
Bi-Botti C
BB
Youan
D000925:Anticoagulants / Q000008:administration & dosage*; D003627:Data Interpretation, Statistical; D004337:Drug Carriers / Q000737:chemistry; D004655:Emulsions; D005079:Excipients / Q000737:chemistry; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage*; D019344:Lactic Acid / Q000737:chemistry*; D008027:Light; D053758:Nanoparticles; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011109:Polymethacrylic Acids / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry; D012044:Regression Analysis; D012542:Scattering, Radiation; D012997:Solvents / Q000737:chemistry; D055672:Static Electricity
D000925:Anticoagulants; D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D006495:Heparin, Low-Molecular-Weight; D011109:Polymethacrylic Acids; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C038300:methylmethacrylate-methacrylic acid copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011142:Polyvinyl Alcohol