Mucoadhesive Buccal Films for Local Delivery of Lactobacillus brevis.

The aim of this work was to prepare mucoadhesive buccal films for local release of Lactobacillus brevis CD2, which shows interesting anti-inflammatory properties due to its high levels of arginine deiminase. Hydroxypropylmethylcellulose-based films were prepared by means of a modified casting method, which allowed L. brevis CD2 loading on one side of the film, before its complete drying. Three batches of films were prepared, stored at +2-8 °C and +23-25 °C for 48 weeks and characterized in terms of physico-chemical and functional properties. For each batch, the L. brevis viable count and arginine deiminase activity were evaluated at different time points in order to assess functional property maintenance over time. Moreover, the mucoadhesive properties and ability of the films to release L. brevis CD2 were evaluated. A good survival of L. brevis CD2 was observed, particularly at the storage temperature of +2-8 °C, while the activity of arginine deiminase was maintained at both temperature values. Films showed good mucoadhesive properties and guaranteed a prolonged release of viable lactobacilli, which can be directed towards the whole buccal cavity or specific mucosa lesions. In conclusion, the proposed preparative method can be successfully employed for the production of buccal films able to release viable L. brevis CD2 cells that maintain the anti-inflammatory enzymatic activity.

Design and evaluation of buccal films as paediatric dosage form for transmucosal delivery of ondansetron.

In the process of implementation and innovation of paediatric dosage forms, buccal films for transmucosal administration of drug represent one of the most interesting approach. In fact, films are able to provide an extended duration of activity allowing minimal dosage and frequency and offer an exact and flexible dose, associated with ease of handling. The objective of the present study was to develop polymeric films for the sustained release of ondansetron hydrochloride, a selective inhibitor of 5-HT3 receptors indicated in paediatrics for the prevention and treatment of nausea and vomiting caused by cytotoxic chemotherapy or radiotherapy and postoperatively. Films were prepared by casting and drying of aqueous solutions containing different weight ratios of hydroxypropylmethylcellulose (HPMC) with chitosan (CH) or sodium hyaluronate (HA) or gelatin (GEL) and characterized for their physico-chemical and functional properties. The presence of HA, GEL and CH did not improve the mucoadhesive properties of HPMC film. The inclusion of GEL and CH in HPMC film increased in vitro drug release with respect to the inclusion of HA, although films containing HA showed the highest water uptake. Moreover in agreement with the release behaviour, the inclusion of CH and GEL provided higher drug permeation through porcine buccal mucosa with respect to HPMC film and ensured linear permeation profiles of drug.

Mucoadhesive Buccal Tablets Based on Chitosan/Gelatin Microparticles for Delivery of Propranolol Hydrochloride.

Propranolol administration through buccal route offers some distinct advantages thanks to the easy access to the oral mucosa, fast onset of action, and avoidance of hepatic and intestinal degradation mechanisms. To overcome the effective removal existing in the buccal cavity, mucoadhesive delivery systems are considered a promising approach as they facilitate a close contact with the buccal mucosa. The aim of this study was to prepare mucoadhesive tablets based on chitosan/gelatin microparticles for buccal delivery of propranolol hydrochloride. Spray-dried microparticles were prepared with different chitosan-gelatin weight ratios and characterized in terms of yield and morphology. Microparticles were subsequently compressed with the drug to obtain loaded buccal tablets. In vitro water uptake, mucoadhesion, release, and permeation tests were performed to investigate tablet ability to hydrate, to adhere to the mucosa, and to deliver drug through buccal mucosa. Microparticles showed a different morphology based on the different chitosan-gelatin weight ratios. Moreover, buccal tablets based on the prepared microparticles showed different technological and functional characteristics in virtue of their composition. In particular, tablets with an excess of chitosan showed the best mucoadhesive properties, allowed the permeation of the greatest drug amount among all formulations, and could be promising for buccal administration of propranolol hydrochloride.

Development and characterization of chitosan/hyaluronan film for transdermal delivery of thiocolchicoside.

The objective of this study was the development of chitosan/hyaluronan transdermal films to improve bioavailability of thiocolchicoside. This approach offers the possibility to elude the first-pass metabolism and at the same time it is able to provide a predictable and extended duration of activity. Films were prepared by casting and drying of aqueous solutions containing different weight ratios of chitosan and hyaluronan and characterized for their physico-chemical and functional properties. In accordance with polymeric composition of films and, therefore, with the amount of the net charge after the complexation, films containing the same weight ratio of chitosan and hyaluronan showed lower water uptake ability with respect to films containing only one polymeric species or an excess of chitosan or hyaluronan. Moreover, the lower the hydration of the polymeric network, the lower is the drug diffusion through the films and its permeation through the skin. This study clearly confirmed that the selection of a suitable polymeric weight ratio and appropriate preparative conditions allows the modulation of film functional properties, suggesting that these formulations could be used as a novel technological platform for transdermal drug delivery.

Antiproliferative effect of linalool on RPMI 7932 human melanoma cell line: ultrastructural studies.

Linalool, a small monoterpene molecule, is used widely for its flavoring and fragrant properties in many cosmetic products. In this work, we investigated the antiproliferative effect of two different linalool solutions on RPMI 7932 human melanoma and NCTC 2544 normal keratinocites cell lines using the trypan blue method. Morphological changes in cells were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In addition, apoptosis was evaluated using caspase 3-antibody. Linalool showed a selective inhibitory effect on the growth of melanoma cells in a concentrationdependent manner, inducing several morphological changes, as revealed by SEM and TEM analysis. Moreover, the labelling for caspase-3 is abundant in the melanoma cells and almost absent in the normal keratinocites cells. The results suggest that linalool could be used as drug and/or as model drug for developing potential therapeutic agents for melanoma.

Vaginal inserts based on chitosan and carboxymethylcellulose complexes for local delivery of chlorhexidine: preparation, characterization and antimicrobial activity.

The aim of this work was to prepare vaginal inserts based on chitosan/carboxymethylcellulose polyelectrolyte complexes for local delivery of chlorhexidine digluconate. Complexes were prepared with different chitosan/carboxymethylcellulose molar ratios at a pH value close to pKa interval of the polymers and were characterized in terms of physico-chemical properties, complexation yield and drug loading. Then complexes were used to prepare inserts as vaginal dosage forms and their physical handling, morphology, water-uptake ability and drug release properties as well as antimicrobial activity toward Candida albicans and Escherichia coli were evaluated. Results confirmed the ionic interaction between chitosan and carboxymethylcellulose and the influence of the charge amount on the complexation yield. Complexes were characterized by high values of drug loading and showed increasing water-uptake ability with the increase of carboxymethylcellulose amount. The selection of appropriate chitosan/carboxymethylcellulose molar ratios allowed to obtain cone-like shaped solid inserts, easy to handle and able to hydrate releasing the drug over time. Finally, the formulated inserts showed antimicrobial activity against common pathogens responsible for vaginal infections.

Formulation of cellulose film containing permeation enhancers for prolonged delivery of propranolol hydrocloride.

The aim of this study was to evaluate the capacity of cellulose films enriched with oleic acid and polysorbate 80 to enhance the transdermal permeation of propranolol hydrochloride. Polymeric films were prepared by casting and drying aqueous solutions of hydroxypropylmethylcellulose or carboxymethylcellulose and characterized in chemical-physical properties, such as drug content, thickness, morphology and water uptake capacity. In vitro transport experiments were performed in order to evaluate the permeation enhancing ability of oleic acid and polysorbate 80. All carboxymethylcellulose films showed lower cumulative amounts of drug permeated than hydroxypropylmethylcellulose. Moreover, films containing both oleic acid and polysorbate 80 provided a greater permeation in comparison to film without permeation enhancers or only with one of these. The results obtained confirm that propranolol hydrochloride permeation can be easily modulated by varying the cellulose and enhancer type used for film preparation.

Microparticles based on chitosan/pectin polyelectrolyte complexes for nasal delivery of tacrine hydrochloride.

The aim of this study was the investigation of powder-based formulations for nasal administration of tacrine hydrochloride. The anti-Alzheimer drug was encapsulated in mucoadhesive microparticles based on chitosan/pectin polyelectrolyte complexes. Microparticles were prepared by means of two different technological approaches (direct spray-drying and spray-drying followed by lyophilization) and analysed in terms of size, morphology and physico-chemical characteristics. Moreover, water uptake and mucoadhesion ability were evaluated as well as drug release and permeation behaviour. The results suggest that lyophilization favours the formation of small particle aggregates with a size of 10 µm, instead of single particles (size smaller than 5 µm) such as direct spray-drying. Particles obtained with the two loading methods present different functional properties according to the different physical state of the loaded drug and its possible interaction with chitosan/pectin complex. Moreover, the presence of different amount of chitosan and pectin in the complex influences their ability to hydrate, interact with mucin and favour drug permeation.

A new physical-chemical process for the efficient production of cellulose fibers from Spanish broom (Spartium junceum L.).

A novel and efficient method for the extraction of cellulose fibers from Spanish broom (Spartium junceum L.) is presented. The method is based on the sequential combination between an initial chemical stage (alkaline digestion) and a subsequent physical-chemical stage, consisting of compression with hot air in an autoclave followed by rapid decompression (DiCoDe process, digestion-compression-decompression). The alkaline mother liquor deriving from the initial digestion step can be conveniently recycled after centrifugation followed by ultrafiltration. The process is characterized by the production of fibers with excellent physical-chemical properties, such as high mechanical resistance and high elasticity, and rapid production times. The fibers obtained after the DiCoDe process can be further softened and whitened by means of enzymatic digestion. Fibers were morphologically characterized by scanning electron microscopy (SEM), while their composition and physical-chemical properties were determined by conventional methods, including colorimetry, TAPPI protocols, IR spectroscopy, and X-ray diffractometry.