title: Development of egg PC/cholesterol/α-tocopherol liposomes with ionic gradients to deliver ropivacaine.
abstract: BACKGROUND
  Ropivacaine (RVC) is an aminoamide local anesthetic widely used in surgical procedures. Studies with RVC encapsulated in liposomes and complexed in cyclodextrins have shown good results, but in order to use RVC for lengthy procedures and during the postoperative period, a still more prolonged anesthetic effect is required.
  
  
  OBJECTIVE
  This study therefore aimed to provide extended RVC release and increased upload using modified liposomes.
  
  
  METHODS
  Three types of vesicles were studied: (i) large multilamellar vesicle (LMV), (ii) large multivesicular vesicle (LMVV) and (iii) large unilamellar vesicle (LUV), prepared with egg phosphatidylcholine/cholesterol/α-tocopherol (4:3:0.07 mol%) at pH 7.4. Ionic gradient liposomes (inside: pH 5.5, pH 5.5 + (NH4)2SO4 and pH 7.4 + (NH4)2SO4) were prepared and showed improved RVC loading, compared to conventional liposomes (inside: pH 7.4).
  
  
  CONCLUSIONS
  An high-performance liquid chromatography analytical method was validated for RVC quantification. The liposomes were characterized in terms of their size, zeta potential, polydispersion, morphology, RVC encapsulation efficiency (EE(%)) and in vitro RVC release. LMVV liposomes provided better performance than LMV or LUV. The best formulations were prepared using pH 5.5 (LMVV 5.5in) or pH 7.4 with 250 mM (NH4)2SO4 in the inner aqueous core (LMVV 7.4in + ammonium sulfate), enabling encapsulation of as much as 2% RVC, with high uptake (EE(%) ∼70%) and sustained release (∼25 h).
  
  
  CONCLUSIONS
  The encapsulation of RVC in ionic gradient liposomes significantly extended the duration of release of the anesthetic, showing that this strategy could be a viable means of promoting longer-term anesthesia during surgical procedures and during the postoperative period.
authors: a Department of Biochemistry and Tissue Biology , Institute of Biology, State University of Campinas, UNICAMP , Campinas , SP , Brazil .
authors: Camila Morais Gonçalves
authors: CM
authors: da Silva
authors: a Department of Biochemistry and Tissue Biology , Institute of Biology, State University of Campinas, UNICAMP , Campinas , SP , Brazil .|b Department of Environmental Engineering , São Paulo State University , Sorocaba , SP , Brazil , and.
authors: Leonardo Fernandes
authors: LF
authors: Fraceto
authors: c Department of Physiological Sciences , Piracicaba Dental School, State University of Campinas, UNICAMP , Piracicaba , SP , Brazil.
authors: Michelle
authors: M
authors: Franz-Montan
authors: a Department of Biochemistry and Tissue Biology , Institute of Biology, State University of Campinas, UNICAMP , Campinas , SP , Brazil .
authors: Verônica Muniz
authors: VM
authors: Couto
authors: a Department of Biochemistry and Tissue Biology , Institute of Biology, State University of Campinas, UNICAMP , Campinas , SP , Brazil .
authors: Bruna Renata
authors: BR
authors: Casadei
authors: a Department of Biochemistry and Tissue Biology , Institute of Biology, State University of Campinas, UNICAMP , Campinas , SP , Brazil .
authors: Cíntia Maria Saia
authors: CM
authors: Cereda
authors: a Department of Biochemistry and Tissue Biology , Institute of Biology, State University of Campinas, UNICAMP , Campinas , SP , Brazil .
authors: Eneida
authors: E
authors: de Paula
mesh_terms: D000577:Amides / Q000008:administration & dosage*; D002784:Cholesterol / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D004531:Eggs; D007477:Ions / Q000737:chemistry; D008081:Liposomes / Q000138:chemical synthesis* / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry*; D000077212:Ropivacaine; D024502:alpha-Tocopherol / Q000737:chemistry*
chemical_list: D000577:Amides; D007477:Ions; D008081:Liposomes; D010713:Phosphatidylcholines; D000077212:Ropivacaine; D002784:Cholesterol; D024502:alpha-Tocopherol
keywords: Drug delivery; encapsulation efficiency; sustained release