Solid lipid nanoparticles loaded with lipoyl-memantine codrug: preparation and characterization.
Solid lipid nanoparticles (SLNs) are considered very attractive drug-delivery systems (DDS) able to enhance the efficacy of some therapeutic agents in several pathologies difficult to treat in a conventional way. Starting from these evidences, this study describes the preparation, physicochemical characterization, release, and in vitro cytotoxicity of stealth SLNs as innovative approach to improve solubility and absorption through the gastrointestinal tract of lipoyl-memantine (LA-MEM), a potential anti-Alzheimer codrug. Physico-chemical properties of LA-MEM loaded SLNs have been intensively investigated. Differential scanning calorimetry (DSC) was used to clarify the state and crystalline structure of the formulation. The results obtained from particles size analysis, polydispersity (PDI), and zeta potential measurements allowed the identification of the optimized formulation, which was characterized by a drug-lipid ratio 1:5, an average intensity diameter of 170nm, a PDI of 0.072, a zeta potential of -33.8mV, and an entrapment efficiency of 88%. Moreover, in vitro stability and release studies in both simulated gastric fluid (SGF) and simulated intestinal fluid (SIF), and preliminary in vitro cytotoxicity studies revealed that LA-MEM loaded SLNs could represent potential candidate for an in vivo investigation as DDS for the brain since it resulted devoid of citotoxicity and able to release the free codrug.
Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
Sara
S
Laserra
Department of Pharmaceutics, UCL School of Pharmacy, University College London, WC1N 1AX London, UK.
Abdul
A
Basit
Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
Piera
P
Sozio
Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
Lisa
L
Marinelli
Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
Erika
E
Fornasari
Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
Ivana
I
Cacciatore
Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
Michele
M
Ciulla
Department of Molecular Biology and Genetics, Erzurum Technical University, Erzurum 25240, Turkey.
Hasan
H
Türkez
Ataturk University, Faculty of Science, Biology Department, 25240 Erzurum, Turkey.
Fatime
F
Geyikoglu
Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy. Electronic address: adistefano@unich.it.
Antonio
A
Di Stefano
D000818:Animals; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004337:Drug Carriers; D004355:Drug Stability; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry* / Q000633:toxicity; D005750:Gastric Juice / Q000737:chemistry; D006801:Humans; D007419:Intestinal Secretions / Q000737:chemistry; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D008559:Memantine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D053758:Nanoparticles; D036103:Nanotechnology; D018384:Oxidative Stress / Q000187:drug effects; D010316:Particle Size; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D008063:Thioctic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity
D004337:Drug Carriers; D018691:Excitatory Amino Acid Antagonists; D008055:Lipids; C000604149:lipoyl-memantine; D008063:Thioctic Acid; D008559:Memantine
Alzheimer’s disease; Codrug; Lipoic acid; Memantine; Solid lipid nanoparticles