title: Formulation, characterization and cytotoxicity studies of alendronate sodium-loaded solid lipid nanoparticles.
abstract: OBJECTIVE
  Solid lipid nanoparticles (SLNs) are novel drug delivery system for drug targeting in various routs of administration such as parenteral, oral, ophthalmic and topical. These carriers have some advantages such as high drug payload, increased drug stability, the possibility of incorporation of lipophilic and hydrophilic drugs, and low biotoxicity. In this study, alendronate sodium was used as a hydrophilic model drug and was incorporated into SLNs.
  
  
  METHODS
  Hot homogenization method was used for preparation of alendronate sodium-loaded SLN formulations and the encapsulation efficiency of drug in SLNs was determined by ultrafiltration method using centrifugal devices. Scanning electron microscopy (SEM) was carried out to study the morphological behaviors of prepared SLNs like sphericity. Several cytotoxicity studies including MTT, DAPI staining and DNA fragmentation assays were used for biocompatibility assays.
  
  
  RESULTS
  High drug encapsulation efficiency (70-85%) was achieved by drug determination through derivatization with o-phthalaldehyde. The physical stability of drug-loaded SLNs in aqueous dispersions was assessed in terms of size and drug leakage during two weeks. Scanning electron microscopy images showed spherical particles in the nanometer range confirming the obtained data from size analyzer. Several cytotoxicity studies including MTT, DAPI staining and DNA fragmentation assays as well as flow cytometry analysis confirmed the low toxicity of alendronate-loaded SLNs.
  
  
  CONCLUSIONS
  The cost-efficient procedure, the avoidance of organic solvents application, acceptable reproducibility, ease of manufacturing under mild preparation conditions, high level of drug encapsulation, desirable physical stability and biocompatibility are the advantages of the proposed SLN formulations.
authors.affiliation: Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran; Student research committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Jafar
authors.initials: J
authors.lastname: Ezzati Nazhad Dolatabadi
authors.affiliation: Pharmaceutical Technology Laboratory, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hamed
authors.initials: H
authors.lastname: Hamishehkar
authors.affiliation: Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran; Student research committee, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Morteza
authors.initials: M
authors.lastname: Eskandani
authors.affiliation: Pharmaceutical Technology Laboratory, Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: valizadeh@tbzmed.ac.ir.
authors.forename: Hadi
authors.initials: H
authors.lastname: Valizadeh
mesh_terms: D019386:Alendronate / Q000494:pharmacology*; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D005434:Flow Cytometry; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000378:metabolism; D008055:Lipids / Q000633:toxicity*; D053758:Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D010316:Particle Size; D013194:Staining and Labeling; D013997:Time Factors
chemical_list: D017304:Annexin A5; D007211:Indoles; D008055:Lipids; C007293:DAPI; D016650:Fluorescein-5-isothiocyanate; D019386:Alendronate
keywords: Alendronate sodium; Compritol; Cytotoxicity; SLN; Solid lipid nanoparticle