title: Lactoferrin bioconjugated solid lipid nanoparticles: a new drug delivery system for potential brain targeting.
abstract: BACKGROUND
  Delivery of drugs to brain is a subtle task in the therapy of many severe neurological disorders. Solid lipid nanoparticles (SLN) easily diffuse the blood-brain barrier (BBB) due to their lipophilic nature. Furthermore, ligand conjugation on SLN surface enhances the targeting efficiency. Lactoferin (Lf) conjugated SLN system is first time attempted for effective brain targeting in this study.
  
  
  OBJECTIVE
  Preparation of Lf-modified docetaxel (DTX)-loaded SLN for proficient delivery of DTX to brain.
  
  
  METHODS
  DTX-loaded SLN were prepared using emulsification and solvent evaporation method and conjugation of Lf on SLN surface (C-SLN) was attained through carbodiimide chemistry. These lipidic nanoparticles were evaluated by DLS, AFM, FTIR, XRD techniques and in vitro release studies. Colloidal stability study was performed in biologically simulated environment (normal saline and serum). These lipidic nanoparticles were further evaluated for its targeting mechanism for uptake in brain tumour cells and brain via receptor saturation studies and distribution studies in brain, respectively.
  
  
  RESULTS
  Particle size of lipidic nanoparticles was found to be optimum. Surface morphology (zeta potential, AFM) and surface chemistry (FTIR) confirmed conjugation of Lf on SLN surface. Cytotoxicity studies revealed augmented apoptotic activity of C-SLN than SLN and DTX. Enhanced cytotoxicity was demonstrated by receptor saturation and uptake studies. Brain concentration of DTX was elevated significantly with C-SLN than marketed formulation.
  
  
  CONCLUSIONS
  It is evident from the cytotoxicity, uptake that SLN has potential to deliver drug to brain than marketed formulation but conjugating Lf on SLN surface (C-SLN) further increased the targeting potential for brain tumour. Moreover, brain distribution studies corroborated the use of C-SLN as a viable vehicle to target drug to brain. Hence, C-SLN was demonstrated to be a promising DTX delivery system to brain as it possessed remarkable biocompatibility, stability and efficacy than other reported delivery systems.
authors.affiliation: a Department of Pharmaceutics , National Institute of Pharmaceutical Education and Research (NIPER) , Hyderabad , Andhra Pradesh , India .
authors.forename: Indu
authors.initials: I
authors.lastname: Singh
authors.affiliation: a Department of Pharmaceutics , National Institute of Pharmaceutical Education and Research (NIPER) , Hyderabad , Andhra Pradesh , India .
authors.forename: Rajan
authors.initials: R
authors.lastname: Swami
authors.affiliation: b Medicinal Chemistry and Pharmacology Division , Council of Scientific and Industrial Research-Indian Institute of Chemical Technology (CSIR-IICT) , Hyderabad , Andhra Pradesh , India , and.
authors.forename: Deep
authors.initials: D
authors.lastname: Pooja
authors.affiliation: c Department of Pharmacology , National Institute of Pharmaceutical Education and Research (NIPER) , Hyderabad , Andhra Pradesh , India.
authors.forename: Manish Kumar
authors.initials: MK
authors.lastname: Jeengar
authors.affiliation: a Department of Pharmaceutics , National Institute of Pharmaceutical Education and Research (NIPER) , Hyderabad , Andhra Pradesh , India .
authors.forename: Wahid
authors.initials: W
authors.lastname: Khan
authors.affiliation: a Department of Pharmaceutics , National Institute of Pharmaceutical Education and Research (NIPER) , Hyderabad , Andhra Pradesh , India .|b Medicinal Chemistry and Pharmacology Division , Council of Scientific and Industrial Research-Indian Institute of Chemical Technology (CSIR-IICT) , Hyderabad , Andhra Pradesh , India , and.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism; D045744:Cell Line, Tumor; D000077143:Docetaxel; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D004355:Drug Stability; D005260:Female; D007781:Lactoferrin / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D051379:Mice; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010316:Particle Size; D011869:Radioligand Assay; D043823:Taxoids / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: C490098:LTF protein, human; D043823:Taxoids; D000077143:Docetaxel; D007781:Lactoferrin
keywords: Blood–brain barrier; brain; conjugation; docetaxel; lactoferrin; nanoparticles