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In this study, gellan gum (GG), a natural polysaccharide, was used to fabricate spherical porous beads suitable as sustained drug delivery systems for oral administration. GG was cross-linked with calcium ions to prepare polymeric beads. Rheological studies and preliminary experiments of beads preparation allowed to identify the GG and the CaCl2 concentrations suitable for obtaining stable and spherical particles. GG beads were formed, through ionotropic gelation technique, with and without the presence of the synthetic clay laponite. The resultant beads were analyzed for dimensions (before and after freeze-drying), morphological aspects and ability to swell in different media miming biological fluids, namely SGF (Simulated Gastric Fluid, HCl 0.1 M) and SIF (Simulated Intestinal Fluid, phosphate buffer, 0.044 M, pH 7.4). The swelling degree was lower in SGF than in SIF and further reduced in the presence of laponite. The GG and GG-layered silicate composite beads were loaded with two model drugs having different molecular weight, namely theophylline and cyanocobalamin (vitamin B12) and subjected to in-vitro release studies in SGF and SIF. The presence of laponite in the bead formulation increased the drug entrapment efficiency and slowed-down the release kinetics of both drugs in the gastric environment. A moving-boundary swelling model with “diffuse” glassy-rubbery interface was proposed in order to describe the swelling behavior of porous freeze-dried beads. Consistently with the swelling model adopted, two moving-boundary drug release models were developed to interpret release data from highly porous beads of different drugs: drug molecules, e.g., theophylline, that exhibit a typical Fickian behavior of release curves and drugs, such as vitamin B12, whose release curves are affected by the physical/chemical interaction of the drug with the polymer/clay complex. Theoretical results support the experimental observations, thus confirming that laponite may be an effective additive for fabricating sustained drug delivery systems.

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Polymeric oral thin films (OTFs) were prepared by the casting method, combining gellan gum (GG), a water-soluble polysaccharide, and glycerol (Gly) as a plasticizing agent. GG-Gly films were investigated as potential systems for buccal drug delivery using fluconazole (Class I of the Biopharmaceutical Classification System) as a model drug. At a low concentration of Gly drug precipitation occurred while, for higher concentrations of Gly, a significant deterioration of mucoadhesive and mechanical properties was observed. One possible way to overcome all these problems could be the addition of hydroxypropyl-β-cyclodextrin (HP-β-CD) to the GG-Gly formulation as a drug-precipitation inhibitor. In this work the effect of cyclodextrin addition on the mechanical, mucoadhesive, swelling and release properties of GG-Gly films was investigated. In-vitro drug release studies were carried out using the paddle type dissolution apparatus (USP II) and the millifluidic flow-through device (MFTD). A moving-boundary model for swelling dynamics and release in USP II is proposed to estimate the effective diffusivity of the solvent, HP-β-CD, fluconazole and complex fluconazole/HP-β-CD in the swelling film. Experimental results, supported by theoretical modeling, confirmed that gellan gum-low glycerol thin films including HP-β-CD represent a suitable formulation for fluconazole drug delivery. A sustained release was observed when GG-Gly film is loaded with a preformed complex fluconazole/HP-β-CD.

Lavandin essential oil (LEO), a natural sterile hybrid obtained by crossbreeding L. angustifolia × L. latifolia, is mainly composed by active components belonging to the family of terpenes endowed with relevant anti-proliferative activity, which can be enhanced by proper application of nanotechnology. In particular, this study reports the chemical characterization and the screening of the anti-proliferative activity on different human cell lines of pure and nano-formulated lavandin essential oil (EO). LEO and its formulation (NanoLEO) were analyzed by HS/GC-MS (Headspace/Gas Chromatography-Mass Spectrometry) to describe and compare their chemical volatile composition. The most abundant compounds were linalool and 1,8-cineole (LEO: 28.6%; 27.4%) (NanoLEO: 60.4%; 12.6%) followed by α-pinene (LEO: 9.6%; NanoLEO: 4.5%), camphor (LEO: 6.5%; NanoLEO: 7.0%) and linalyl acetate (LEO: 6.5%; NanoLEO: 3.6%). The cytotoxic effects of LEO and NanoLEO were investigated on human neuroblastoma cells (SHSY5Y), human breast adenocarcinoma cells (MCF-7), human lymphoblastic leukemia cells (CCRF CEM), human colorectal adenocarcinoma cells (Caco-2) and one normal breast epithelial cell (MCF10A) by the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide)-assay. Caco-2, MCF7 and MCF10A normal cells resulted more resistant to the treatment with LEO, while CCRF-CEM and SHSY5Y cells were more sensitive. The antiproliferative effect of LEO resulted amplified when the essential oil was supplied as nanoformulation, mainly in Caco-2 cells. Scanning and transmission electron microscopy investigations were carried out on Caco-2 cells to outline at ultrastructural level possible affections induced by LEO and NanoLEO treatments.