Development and Characterization of Azithromycin-Loaded Microemulsions: A Promising Tool for the Treatment of Bacterial Skin Infections

In recent years, the treatment of bacterial skin infections has been considered a major healthcare issue due to the growing emergence of antibiotic-resistant strains of Staphylococcus aureus. The incorporation of antibiotics in appropriate nanosystems could represent a promising strategy, able to overcome several drawbacks of the topical treatment of infections, including poor drug retention within the skin. The present work aims to develop microemulsions containing azithromycin (AZT), a broad-spectrum macrolide antibiotic. Firstly, AZT solubility in various oils, surfactants and co-surfactants was assessed to select the main components. Subsequently, microemulsions composed of vitamin E acetate, Labrasol (R) and Transcutol (R) P were prepared and characterized for their pH, viscosity, droplet size, zeta potential and ability to release the drug and to promote its retention inside porcine skin. Antimicrobial activity against S. aureus methicillin-resistant strains (MRSA) and the biocompatibility of microemulsions were evaluated. Microemulsions showed an acceptable pH and were characterized by different droplet sizes and viscosities depending on their composition. Interestingly, they provided a prolonged release of AZT and promoted its accumulation inside the skin. Finally, microemulsions retained AZT efficacy on MRSA and were not cytotoxic. Hence, the developed AZT-loaded microemulsions could be considered as useful nanocarriers for the treatment of antibiotic-resistant infections of the skin

Design and Characterization of an Ethosomal Gel Encapsulating Rosehip Extract

: Rising environmental awareness drives green consumers to purchase sustainable cosmetics based on natural bioactive compounds. The aim of this study was to deliver Rosa canina L. extract as a botanical ingredient in an anti-aging gel using an eco-friendly approach. Rosehip extract was first characterized in terms of its antioxidant activity through a DPPH assay and ROS reduction test and then encapsulated in ethosomal vesicles with different percentages of ethanol. All formulations were characterized in terms of size, polydispersity, zeta potential, and entrapment efficiency. Release and skin penetration/permeation data were obtained through in vitro studies, and cell viability was assessed using an MTT assay on WS1 fibroblasts. Finally, ethosomes were incorporated in hyaluronic gels (1% or 2% w/v) to facilitate skin application, and rheological properties were studied. Rosehip extract (1 mg/mL) revealed a high antioxidant activity and was successfully encapsulated in ethosomes containing 30% ethanol, having small sizes (225.4 ± 7.0 nm), low polydispersity (0.26 ± 0.02), and good entrapment efficiency (93.41 ± 5.30%). This formulation incorporated in a hyaluronic gel 1% w/v showed an optimal pH for skin application (5.6 ± 0.2), good spreadability, and stability over 60 days at 4 °C. Considering sustainable ingredients and eco-friendly manufacturing technology, the ethosomal gel of rosehip extract could be an innovative and green anti-aging skincare product

Gli antiossidanti nella pratica erboristica

Il Corso di Laurea in Tecniche Erboristiche della Facolt\ue0 di Farmacia dell\u2019Universit\ue0 di Bologna propone periodicamente, nella sua sede di Imola, incontri di approfondimento aperti non solo agli studenti ed ai professionisti del settore, ma a chiunque sia interessato a conoscere impieghi e propriet\ue0 delle piante officinali. L\u2019argomento scelto in questa occasione, lo stress ossidativo, verr\ue0 sviluppato dai vari relatori sulla base di esperienze professionali diverse allo scopo di fornire un quadro quanto pi\uf9 aggiornato e completo circa propriet\ue0 e limiti dei prodotti comunemente proposti per contrastare tale processo

Innovative drug systems for delivery of drugs for which bioavailability is critical

Numerosi farmaci presentano solubilit\ue0, stabilit\ue0, permeabilit\ue0 che ostacolano lo sviluppo di una forma di somministrazione non parenterale. E' pressante pertanto la necessit\ue0 di prevedere nuove vie e strategie di somministrazione per superare tali problematiche senza ricorrere a modifiche chimiche di tali farmaci che originerebbero una sostanza completamente nuova. La tecnologia farmaceutica oltre a valutare vie di somministrazione alternative a quella parenterale \ue8 in grado di realizzare sistemi supramolecolari capaci di mascherare la struttura molecolare del farmaco aiutandolo a superare passaggi critici per la sua disponibilit\ue0 biologica. In particolare, le nano/microtecnologie farmaceutiche consentono la fabbricazione di particelle da usare come vettori che, per la loro struttura e composizione, possono modificare il destino del farmaco. Un\u2019ampia sezione della nostra ricerca \ue8 rivolta allo studio di sistemi farmaceutici (nano/microsfere, nano/microcapsule, micelle polimeriche e sistemi macromolecolari) per il rilascio di farmaci che presentano gravi difetti biofarmaceutici e farmacocinetici, che potrebbero essere risolti con la loro inclusione in vettori. In particolare, attualmente si stanno realizzando vettori a destabilizzazione sito-specifica per la veicolazione di farmaci a struttura peptidica, costituiti da materiali biocompatibili e/o biodegradabili in grado di promuovere un rilascio selettivo del farmaco nell\u2019ambiente caratteristico del sito di trattamento o di assorbimento

New environmental sensitive system for colon-specific delivery of peptidic drugs.

Colon specific drug delivery systems have gained increased importance for systemic and local delivery of protein and peptide drugs. Vancomycin, a peptidic drug, in the treatment of pseudomembranous colitis must be given orally to reach the site of infection. To achieve successful colonic delivery, vancomycin needs to be protected from degradation in the environment of the upper gastrointestinal tract and then be abruptly released into the colon. This work describes the use of thermally crosslinked bovine serum albumin (BSA) nanospheres (NS) coated with different fatty acids as carriers able to control the release of vancomycin (Vanco) in the colon environment responding strongly to stimuli such as pH, mucin interactions and enzyme digestion

Preparazioni erboristiche e fitocosmetiche. Aspetti formulativi e metodologie produttive.

Le piante rappresentano una fonte preziosa per la produzione di prodotti con finalit\ue0 salutistiche, nutrizionali e cosmetiche. Ci\uf2 avviene in armonia con l\u2019evoluzione del concetto di salute, un tempo inteso unicamente come assenza di malattia, oggi sempre pi\uf9 associato alla ricerca di completo benessere fisico e mentale. In questa prospettiva l\u2019utilizzo del substrato vegetale rappresenta un riferimento importante in tutti gli approcci rivolti alla prevenzione delle malattie, al mantenimento dello stato di benessere psico-fisico, al potenziamento delle difese dell\u2019organismo ed al miglioramento del proprio aspetto. Il processo produttivo, che partendo dal substrato vegetale permette di ottenere il prodotto finito, prevede la definizione di un\u2019opportuna forma di dosaggio in grado di garantire la cessione delle sostanze funzionali nel modo pi\uf9 appropriato. In ambito erboristico, questo processo di produzione del prodotto finito fa riferimento, fondamentalmente, a tecnologie analoghe a quelle utilizzate nel settore farmaceutico, riproponendone anche gli aspetti pi\uf9 innovativi, quali la preparazione di sistemi particellari (micro/nanosfere, micro/nanocapsule, liposomi ecc.). Come esempio degli aspetti preparativi e delle prospettive d\u2019impiego dei sistemi particellari, in ambito erboristico e fitocosmetico, descriviamo la realizzazione di microcapsule contenenti oli essenziali. Ricordiamo che le microcapsule sono strutture formate da un nucleo centrale, contenente la sostanza funzionale in forma liquida o solida, circondato da una membrana polimerica. Questi sistemi si differenziano dalle microsfere che sono costituite da una matrice polimerica o lipidica solida, contenente la sostanza attiva disciolta o finemente dispersa. Entrambe queste formulazioni possono essere utilizzate in campo erboristico non solo per migliorare la stabilit\ue0, la sicurezza d\u2019impiego e le caratteristiche organolettiche delle sostanze incapsulate, ma anche per aumentarne la biodisponibilit\ue0 ed eventualmente garantirne un rilascio modificato. I sistemi microparticellari rispondono quindi adeguatamente alla necessit\ue0 di superare alcuni inconvenienti legati all\u2019utilizzo delle sostanze vegetali che sono spesso caratterizzate da scarsa solubilit\ue0, difficile assorbimento, instabilit\ue0 chimica, sapore ed odore sgradevoli. Le preparazioni che riportiamo hanno come obiettivo l\u2019incapsulamento, mediante spray-drying, di una frazione lipofila, generalmente un olio essenziale, all\u2019interno di una struttura di contenimento idrofila, quale un polimero di origine naturale o sintetica. Gli oli che sono stati presi in considerazione sono l\u2019olio di Neem e l\u2019olio di mirto australiano, utilizzando come materiali di rivestimento l\u2019alcool polivinilico e la pectina associati alla gomma arabica. L\u2019olio di Neem \ue8 stato cos\uec migliorato nelle sue caratteristiche organolettiche e protetto da fenomeni di degradazione ambientale; mentre le microcapsule di olio di mirto sono state proposte per potenziare le propriet\ue0 antimicrobiche dell\u2019olio nell\u2019ambito di una formulazione fitocosmetica

Hydrogel vehicles for hydrophilic compounds.

Hydrogels date back to 1960 when Wichterle and Lim first proposed the use of hydrophilic networks of poly(2-hydroxyethylmethacrylate) (PHEMA) in contact lenses (Wichterle and Lim 1960).Since then, the use of hydrogels has extended to various biomedical (Hoffman 2002; Peppas et al. 2006; Kopeceka 2007) and pharmaceutical (Peppas 2000) applications. In particular, due to their physical properties similar to those of human tissues (water content, soft and pliable consistence) hydrogels have been used for different administration routes such as oral, rectal, ocular, epidermal and subcutaneous (Peppas 2000; Guy 1996; Jatav et al. 2011). Hydrogels are composed of hydrophilic macromolecules forming three-dimensional insoluble networks able to imbibe large amounts of water or biological fluids (Peppas and Mikos 1986). Commonly, the polymers utilized to make hydrogels are insoluble due to the presence of permanent or reversible crosslinks (Berger 2004). Permanent crosslinked hydrogels (Wichterle and Lim 1960; Xiao and Zhou 2003; Brasch and Burchard 1996) are characterized by covalent bonds forming tie-points or junctions, whereas reversible crosslinked hydrogels (Watanabe et al. 1996; Wang et al. 1999; Qu et al. 1999) present ionic, hydrophobic, or coiled-coil physical interactions. These kinds of crosslinks in the polymer structure yield insoluble materials able to swell in aqueous environments retaining a significant fraction of water in their structure, up to thousands of times their dry weight in water. Hydrogels can be divided into homopolymer or copolymers based on the preparative method, but they can also be natural polymers, synthetic polymers or derivatives. In nature hydrogels can be found in plants (pectin, pullulan), various species of brown seaweed (alginic acid, agar, carrageenan), crustaceans (chitin) and animal tissue (hyaluronic acid, collagen, fibrin). Typical simple synthetic materials applied for general-purpose hydrogels are poly(ethylene oxide), poly(vinyl alcohol), poly(vinyl pyrrolidone), poly(hydroxyethyl methacrylate) and poly(N-isopropyl acrylamide). Moreover, the synthetic pathway offers more possibilities to create hydrogels with modified functional properties. In fact, several physiologically-responsive hydrogels are obtained from chemical or physical modifications of natural and synthetic polymers and tested for use in the so-called "intelligent biomaterials" (Hoffmann 1991; Miyata et al. 2002; Murdan 2003; Chen et al. 2004) because they are capable of reacting to various environmental stimuli (temperature, pH, ionic strength, solute concentration, electric radiation, light, sound, etc.). Hydrogels can be homogeneous, when the pores between polymer chains are the only spaces available for mass transfer and the pore size is within the range of molecular dimensions (a few nanometers or less), or porous when the effective pore size is over 10 nm. In homogeneous hydrogels the transfer of water or other solutes is achieved by a pure diffusional mechanism, which restricts the rate of absorption and to some extent the size of species that are absorbed. Porous hydrogels can be made by different polymerization methods in the presence of dispersed porosigens (ice crystals, oil, sucrose crystals) which can be removed later to leave an interconnected meshwork, where the pore size depends on the size of the porosigens (Hickey and peppas 1995). The introduction of a porosigen reduces mechanical strength significantly making porous hydrogels weaker than homogeneous hydrogels. In medical, engineering and pharmaceutical technology, hydrogel degradation is considerable important. In fact, investigators have focused on controlling degradation behavior of hydrogels to design polymers able to be cleared from the body once they complete their roles (Anderson and Shive 1997; Timmer et al. 2002): for this reason labile bonds are frequently introduced in the gels. These bonds can be present either in the polymer backbone or in the crosslinks used to prepare the gel. The labile bonds can be broken under physiological conditions either enzymatically or chemically, in most cases by hydrolysis (Damink et al. 1996; Eliaz and Kost 2000; Lee et al. 2004)

Microencapsulation Strategies for Essential Oils - A Review

Throughout history the main aims of microencapsulation of essential oils has been to protect them against degradation caused by environmental factors, improve their solubility end efficacy, mask or enhance their taste, turn them into stable compounds and ensure their release with specific mechanisms suggested by the microcapsule shell and core characteristics. Essential oil microencapsulation processes are commonly based on the principle of oil-in-water (o/w)-emulsion formulation and subsequent conversion into a solid form by different technological methods. With this aim, various technologies have been examined for microcapsule preparation including complex coacervation, spray-drying and interfacial polycondensation. This article reviews the current state of the art in essential oil microencapsulation techniques focusing on process-related aspects of both well-established and more advanced technologies

Self-assembling poly(vinyl alcohol) derivatives, interactions with drugs and control of release

The self-assembling properties of poly(vinyl alcohol) substituted with 2-hydroxypropyltrimethylammonium and with acyl chains of different molecular weights (butyryl, capryloyl, lauroyl, or myristoyl) were evaluated to assess the conditions favoring interaction with a poorly soluble drug such as indomethacin to increase its availability. To evaluate the effect of drug-polymer interactions on the solubility of the drug, phase-solubility diagrams were obtained from each substituted polymer at pH 2.0, 5.5, and 7.4 in the presence of indomethacin. To evaluate the availability of the free drug in solution, release profiles of the free drug from drug-polymer physical mixtures were obtained by a dissolution-diffusion apparatus containing a dialysis membrane allowing diffusion of the free drug towards a receiving phase where its concentration was determined over time. The phase-solubility diagrams revealed increasing drug solubility on increasing the polymer concentration. The drug-polymer affinity was slightly increased by lengthening the chain of the substituent on the polymer and was strongly increased by raising the pH of the aqueous phase. The thermodynamic evaluation of the drug-polymer interactions indicated that the interaction is enthalpically driven while the increase in drug-polymer affinity with increasing chain length could be attributed to an entropic contribution. The free drug availability from the drug-polymer systems increased on enhancing the drug-polymer affinity because it corresponded to an increase in the solubilizing effect of the polymer on the drug. © 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association

Chitosan salts as nasal sustained delivery systems for peptidic drugs

The aim of this study was to describe a sustained drug release system based on chitosan salts for vancomycin hydrochloride delivery. Chitosan lactate, chitosan aspartate, chitosan glutamate and chitosan hydrochloride were prepared by spray-drying technique. Vancomycin hydrochloride was used as a model peptidic drug, the nasal sustained release of which should avoid first-pass metabolism in the liver. This in-vitro study evaluated the influence of chitosan salts on the release behaviour of vancomycin hydrochloride from the physical mixtures at pH 5.5 and 7.4. In-vitro release of vancomycin was retarded by chitosan salts and, in particular, chitosan hydrochloride provided the lowest release of vancomycin