Design, Evaluation and Comparison of Nanostructured Lipid Carriers and Chitosan Nanoparticles as Carriers of Poorly Soluble Drugs to Develop Oral Liquid Formulations Suitable for Pediatric Use

There is a serious need of pediatric drug formulations, whose lack causes the frequent use of extemporaneous preparations obtained from adult dosage forms, with consequent safety and quality risks. Oral solutions are the best choice for pediatric patients, due to administration ease and dosage-adaptability, but their development is challenging, particularly for poorly soluble drugs. In this work, chitosan nanoparticles (CSNPs) and nanostructured lipid carriers (NLCs) were developed and evaluated as potential nanocarriers for preparing oral pediatric solutions of cefixime (poorly soluble model drug). The selected CSNPs and NLCs showed a size around 390 nm, Zeta-potential > 30 mV, and comparable entrapment efficiency (31–36%), but CSNPs had higher loading efficiency (5.2 vs. 1.4%). CSNPs maintained an almost unchanged size, homogeneity, and Zeta-potential during storage, while NLCs exhibited a marked progressive Zeta-potential decrease. Drug release from CSNPs formulations (differently from NLCs) was poorly affected by gastric pH variations, and gave rise to a more reproducible and controlled profile. This was related to their behavior in simulated gastric conditions, where CSNPs were stable, while NLCs suffered a rapid size increase, up to micrometric dimensions. Cytotoxicity studies confirmed CSNPs as the best nanocarrier, proving their complete biocompatibility, while NLCs formulations needed 1:1 dilution to obtain acceptable cell viability values.

2.1. Materials

Precirol^® ATO5 (glyceryl distearate), Transcutol^® HP (highly purified diethylene glycol monoethyl ether), Transcutol^® P (purified diethylene glycol monoethyl ether) Compritol^® 888ATO (glyceryl dibehenate), Gelucire^® 48/16 (polyoxyl-32 stearate (type I), Geleol^® (glycerol monostearate), Labrafac^® Lipophile WL 1349 (caprylic triglyceride, medium chain triglycerides), Labrasol^® (caprylocaproyl polyoxyl-8 glycerides), Labrasol^® ALF (caprylocaproyl polyoxyl-8 glycerides), and cetyl palmitate were kindly provided by Gattefossé (Saint-Priest, Cedex, France). Imwitor^® 491 (glyceryl monostearate), Imwitor^® 988 (glyceryl monocaprylate), Miglyol^® 810N (caprylic triglyceride), and Miglyol^® 812 (caprylic triglyceride) were supplied by IOI Oleo GmbH (Hamburg, Germany). Glyceryl tripalmitate, Pluronic^® F68 (poloxamer 188), stearylamine, low-molecular weight chitosan (CS, 50–190 kDa, 75–85% deacetylation degree), tripolyphosphate, 3(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), propidium iodide (PI), sodium dodecyl sulphate (SDS), and dimethylsulfoxide (DMSO) were purchased from Sigma-Aldrich (St. Louis, MO, USA). Cefixime trihydrate (CEF) was a kind gift from Menarini (Florence, Italy). Purified water was obtained by inverse osmosis (Elix 3, Millipore SAS, Molsheim, France). All other chemicals were of analytical grade.

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Nerli, G.; Gonçalves, L.M.D.; Cirri, M.; Almeida, A.J.; Maestrelli, F.; Mennini, N.; Mura, P.A. Design, Evaluation and Comparison of Nanostructured Lipid Carriers and Chitosan Nanoparticles as Carriers of Poorly Soluble Drugs to Develop Oral Liquid Formulations Suitable for Pediatric Use. Pharmaceutics 2023, 15, 1305.
https://doi.org/10.3390/pharmaceutics15041305

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