title: Novel tretinoin formulations: a drug-in-cyclodextrin-in-liposome approach.
abstract: OBJECTIVE
  The aims of this experimental work were the incorporation and full characterization of the system Tretinoin-in-dimethyl-beta-cyclodextrin-in-ultradeformable vesicles (Tretinoin-CyD-UDV) and Tretinoin-in-ultradeformable vesicles (Tretinoin-UDV).
  
  
  METHODS
  The Tretinoin-CyD complex was prepared by kneading and the UDV by adding soybean phosphatidylcholine (SPC) to Tween® 80 followed by an appropriate volume of sodium phosphate buffer solution to make a 10%-20% lipid suspension. The resulting suspension was brought to the final mean vesicles size, of approximately 150 nm, by sequential filtration. The physicochemical characterization was based on: the evaluation of mean particle size and polydispersity index (PI) measured by photon correlation spectroscopy (PCS) and atomic force microscopy (AFM) topographic imaging; zeta potential (ζ-potential) and the SPC concentration determined by Laser-Doppler anemometry and an enzymatic-colorimetric test, respectively. The quantification of the incorporated Tretinoin and its chemical stability (during preparation and storage) was assayed by a HPLC at 342 nm.
  
  
  RESULTS
  It was possible to obtain the system Tretinoin-CyD-UDV. The mean vesicle size was the most stable parameter during experiments time course. AFM showed that Tretinoin-CyD-UDV samples were very heterogeneous in size, having three distinct subpopulations, while Tretinoin-UDV samples had only one homogeneous size population. The results of the ζ-potential measurements have shown that vesicle surface charge was low, as expected, presenting negative values. The incorporation efficiency was high, and no significant differences between Tretinoin-CyD-UDV and Tretinoin-UDV were observed. However, only Tretinoin-UDV with 20% lipid concentration formulation remained chemically stable during the evaluation period.
  
  
  CONCLUSIONS
  According to our results, Tretinoin-UDV with 20% lipid concentration seems to be a better approach than Tretinoin-CyD-UDV, attending to the higher chemical stability.
authors: Nanomedicine and Drug Delivery Systems Group of iMed.UL, Universidade de Lisboa, Lisboa, Portugal. andreiaascenso@ff.ul.pt
authors: Andreia
authors: A
authors: Ascenso
authors: Mariana
authors: M
authors: Cruz
authors: Carla
authors: C
authors: Euletério
authors: Filomena A
authors: FA
authors: Carvalho
authors: Nuno C
authors: NC
authors: Santos
authors: Helena C
authors: HC
authors: Marques
authors: Sandra
authors: S
authors: Simões
mesh_terms: D000279:Administration, Cutaneous; D004337:Drug Carriers / Q000378:metabolism; D004355:Drug Stability; D008081:Liposomes / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D010316:Particle Size; D014212:Tretinoin / Q000008:administration & dosage*; D047392:beta-Cyclodextrins / Q000008:administration & dosage*
chemical_list: D004337:Drug Carriers; D008081:Liposomes; D047392:beta-Cyclodextrins; C038119:heptakis(2,6-O-dimethyl)beta-cyclodextrin; D014212:Tretinoin