Solid lipid nanoparticles with and without hydroxypropyl-β-cyclodextrin: a comparative study of nanoparticles designed for colonic drug delivery.
New solid lipid nanoparticles (SLN), composed of Compritol ATO888 (C) and hydroxypropyl-β-cyclodextrin (HP), were developed in order to study a new colon-specific formulation for diclofenac sodium (D) delivery. The prepared batches differ from each other by the molecular ratio between HP and D and by the composition of the matrix. Nanoparticles composed of an exclusively lipid matrix and nanoparticles with an oligomeric and lipid matrix were compared in order to establish the effect of both components on the drug delivery tests performed. The SLN preparation method was based on the oil/water hot homogenization process. Emulsions produced were cooled at room temperature and lyophilized in order to obtain dried nanoparticles; possible damage to nanoparticle shape and size was avoided by the addition of cryoprotectants to the aqueous dispersion of nanoparticles before exsiccation. An in vitro toxicity study was performed using CaCo(2) cells to establish the safety of the prepared SLN. Data obtained showed that production method studied guarantees emulsions composed of nanosized drops which can be dried by lyophilization into SLN with a size range of 300-600 nm. In vitro and ex vivo tests demonstrated that dried SLN can be considered as colon delivery systems; however, the matrix composition as well as the presence of cryoprotectant on their surface influences the release and permeation rate of D. The in vitro toxicity studies indicated that the SLN are well tolerated.
Department of Drug Sciences, University of Sassari, Sassari, Italy.
Gianpiera
G
Spada
Elisabetta
E
Gavini
Massimo
M
Cossu
Giovanna
G
Rassu
Paolo
P
Giunchedi
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000633:toxicity; D004008:Diclofenac / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D004058:Diffusion; D005227:Fatty Acids / Q000737:chemistry*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D013552:Swine
D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D005227:Fatty Acids; D053769:Nanocapsules; D004008:Diclofenac; C086409:glyceryl behenate