QbD guided early pharmaceutical development study: Production of lipid nanoparticles by high pressure homogenization for skin cancer treatment

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dc.contributor.authorAmasya, Gülin
dc.contributor.authorAksu, Buket
dc.contributor.authorBadilli, U.
dc.contributor.authorOnay-Beşikçi, Arzu
dc.contributor.authorTarımcı, Nilüfer
dc.date.accessioned2021-05-15T12:49:56Z
dc.date.available2021-05-15T12:49:56Z
dc.date.issued2019
dc.departmentEczacılık Fakültesi, Farmasötik Teknoloji Anabilim Dalıen_US
dc.description.abstractThis research attempts to bring together the positive aspects of lipid nanoparticles and Quality by Design (QbD) approach for developing a novel drug delivery system for skin cancers and aktinic keratosis. Lipid nanoparticles which is one of the most efficacious options for topical treatment of skin diseases were prepared due to their ability to overcome the complex structure of skin barrier and to enhance the skin penetration. Since the formulation development contains complex variables of active ingredients, raw materials or production method; all the variables of the product should be elaborated. QbD approach which refers to design and develop formulations and manufacturing processes to maintain the prescribed product quality was also successfully adopted to achieve a time- and cost-saving process ensuring a high-quality product. 5-Fluorouracil (5-FU) loaded lipid nanoparticles, both solid lipid nanoparticles and nanostructured lipid carriers, were developed and characterized by following QbD steps. Optimal lipid nanoparticle formulation with guaranteed quality which was within the design space has been reached through the artificial neural networks. The optimal lipid nanoparticle formulation which is a NLC formulation with a mean particle size of 205,8 ± 9,34 nm, narrow size distribution (0.279 ± 0.01) and negative zeta potantial ?30,20 ± 0,92 was produced by high pressure homogenization method. Cytotoxicity profiles of the optimal NLC was determined by cell culture studies on epidermoid carcinoma cells and human keratinocyte cells. Optimal NLC showed significantly higher anticancer effect on epidermoid carcinoma cells than free 5-FU and also less cytotoxicity towards human keratinocyte cells. Optimal NLC was formulated in hydrogel formulation for ease of application which has suitable occlusive and mechanical properties, viscocity and pH for patient complience. The cumulative amount of 5-FU in dermal tissues of rat skin was found 20.11 ± 2.14 ?g/cm2 and 9.73 ± 0.87 ?g/cm2 after application of NLC enriched hydrogel and 5-FU hydrogel respectively. In conclusion, this study showed that a time and cost saving process ensuring a high-quality product can be obtained by QbD guided formulation development study with the help of artificial neural networks. A novel semisolid dosage form enriched by NLC which is promising for topical treatment of skin cancers was developed. © 2019 Elsevier B.V.en_US
dc.description.sponsorship13L3336003 Ankara Universitesien_US
dc.description.sponsorshipThis study was supported by Ankara University Scientific Research Projects Coordination, Ankara, Turkey ( 13L3336003 ).en_US
dc.description.sponsorshipThis study was supported by Ankara University Scientific Research Projects Coordination, Ankara, Turkey (13L3336003).en_US
dc.identifier.doi10.1016/j.ijpharm.2019.03.056
dc.identifier.endpage121en_US
dc.identifier.issn0378-5173
dc.identifier.pmid30935913
dc.identifier.scopus2-s2.0-85063908282
dc.identifier.scopusqualityQ1
dc.identifier.startpage110en_US
dc.identifier.urihttps://doi.org/10.1016/j.ijpharm.2019.03.056
dc.identifier.urihttps://hdl.handle.net/20.500.12939/1151
dc.identifier.volume563en_US
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.institutionauthorAksu, Buket
dc.language.isoen
dc.publisherElsevier B.V.en_US
dc.relation.ispartofInternational Journal of Pharmaceutics
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subject5-Fluorouracil (5-FU)en_US
dc.subjectArtificial Neural Networksen_US
dc.subjectHigh Pressure Homogenizationen_US
dc.subjectNanostructured Lipid Carriersen_US
dc.subjectQuality By Design (QbD)en_US
dc.subjectSkin Penetration/Permeationen_US
dc.subjectSolid Lipid Nanoparticlesen_US
dc.titleQbD guided early pharmaceutical development study: Production of lipid nanoparticles by high pressure homogenization for skin cancer treatment
dc.typeArticle

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