Chitosan—one of the natural multifunctional polymers—due to its unique and versatile biological properties is regarded as a useful compound in medical and pharmaceutical technology. Recently, considerable research effort has been made in order to develop safe and efficient chitosan products. However, the problem of poor stability of chitosan-based systems restricts its practical applicability; thus, it has become a great challenge to establish sufficient shelf-life for chitosan formulations. Improved stability can be assessed by controlling the environmental factors, manipulating processing conditions (e.g., temperature), introducing a proper stabilizing compound, developing chitosan blends with another polymer, or modifying the chitosan structure using chemical or ionic agents. This review covers the influence of internal, environmental, and processing factors on the long-term stability of chitosan products. The aim of this paper is also to highlight the latest developments which enable the physicochemical properties of chitosan-based applications to be preserved upon storage.

Over the last decades, alginates, natural multifunctional polymers, have increasingly drawn attention as attractive compounds in the biomedical and pharmaceutical fields due to their unique physicochemical properties and versatile biological activities. The focus of the paper is to describe biological and pharmacological activity of alginates and to discuss the present use and future possibilities of alginates as a tool in drug formulation. The recent technological advancements with using alginates, issues related to alginates suitability as matrix for three-dimensional tissue cultures, adjuvants of antibiotics, and antiviral agents in cell transplantation in diabetes or neurodegenerative diseases treatment, and an update on the antimicrobial and antiviral therapy of the alginate based drugs are also highlighted.

Abstract:The objective of this work was to design and characterize liquid and solid self-emulsifying drug delivery systems (SEDDS) for poorly soluble atorvastatin. To optimize the composition of liquid atorvastatin-SEDDS, solubility tests, pseudoternary phase diagrams, emulsification studies and other in vitro examinations (thermodynamic stability, droplet size and zeta potential analysis) were performed. Due to the disadvantages of liquid SEDDS (few choices for dosage forms, low stability and portability during the manufacturing process), attempts were also made to obtain solid SEDDS. Solid SEDDS were successfully obtained using the spray drying technique from two optimized liquid formulations, CF3 and OF2. Despite liquid SEDDS formulation, CF3 was characterized by lower turbidity, higher percentage transmittance and better self-emulsifying properties, and based on the in vitro dissolution study it can be concluded that better solubilization properties were exhibited by solid formulation OF2. Overall, the studies demonstrated the possibility of formulating liquid and solid SEEDS as promising carriers of atorvastatin. SEDDS, with their unique solubilization properties, provide the opportunity to deliver lipophilic drugs to the gastrointestinal tract in a solubilized state, avoiding dissolution-a restricting factor in absorption rate of BCS Class 2 drugs, including atorvastatin.

Mucoadhesive gelling systems with tannic acid modified silver nanoparticles were developed for effective treatment of herpes virus infections. To increase nanoparticle residence time after local application, semi solid formulations designed from generally regarded as safe (GRAS) excipients were investigated for their rheological and mechanical properties followed with ex vivo mucoadhesive behavior to the porcine vaginal mucosa. Particular effort was made to evaluate the activity of nanoparticle-based hydrogels toward herpes simplex virus (HSV) type 1 and 2 infection in vitro in immortal human keratinocyte cell line and in vivo using murine model of HSV-2 genital infection. The effect of infectivity was determined by real time quantitative polymerase chain reaction, plaque assay, inactivation, attachment, penetration and cell-to-cell assessments. All analyzed nanoparticle-based hydrogels exhibited pseudoplastic and thixotropic properties. Viscosity and mechanical measurements of hydrogels were found to correlate with the mucoadhesive properties. The results confirmed the ability of nanoparticle-based hydrogels to affect viral attachment, impede penetration and cell-to-cell transmission, although profound differences in the activity evoked by tested preparations toward HSV-1 and HSV-2 were noted. In addition, these findings demonstrated the in vivo potential of tannic acid modified silver nanoparticle-based hydrogels for vaginal treatment of HSV-2 genital infection.

Topical administration of clotrimazole represents the common use therapy in the antimycotic genitourinary tract treatment. Due to the fast self-cleaning action of the vagina, commercially available vaginal dosage forms with clotrimazole cannot assure prolonged contact time with mucosa, therefore the main objective of this study was to develop a dosage form for vaginal administration of clotrimazole using chitosan-a biodegradable and biocompatible derivative of chitin. Tablets mucoadhesive properties were examined using texture analyser under the presence of porcine vaginal mucosa and two different models of adhesive layersmucin gel and gelatine discs. In addition, friability, hardness, swelling behaviour, residence time, surface morphology of the performed tablets, the in vitro release profile of clotrimazole and clotrimazole release kinetics were determined. The release of clotrimazole from formulations with 25 or 40% of chitosan (F2 and F3) followed non Fickian diffusion through chitosan-gel layer and was retarded up to 6 h. Additionally, tablets F2 showed the best results in terms of mucoadhesive properties and appeared to be a good alternative to commercially available antimycotic vaginal dosage forms.

Periodontal diseases are some of the most widespread oral afflictions, and they are labeled as chronic infections caused by the accumulation of bacteria in dental plaque that produces localized inflammation of the periodontium. The use of local drug delivery systems to treat periodontal diseases has received greater attention, because the active substance is targeted directly to the affected area, which minimizes its systemic side effects. Therefore, the purpose of the investigation was to develop and characterize different types of gel formulations-bigel, hydrogel and oleogel-as local delivery systems containing metronidazole (MET), which can be applied to the oral mucosa. The influence of the formulation type on the mechanical, rheological and mucoadhesive properties were examined. Moreover, in vitro release of metronidazole, its ex vivo permeation through buccal porcine mucosa and antimicrobial activity measured by the plate diffusion method were estimated. It was found that the gel formulations obtained were non-Newtonian systems, showing a shear-thinning behavior and thixotropic properties with good textural features such as firmness, compressibility and adhesiveness. Moreover, the preparations designed possessed beneficial mucoadhesive properties. The formulated hydrogels and bigels containing micronized MET were considered as better formulations in terms of drug release and antimicrobial activity compared to commercially available metronidazole ointment. An ex vivo permeation study with the use of porcine buccal mucosa demonstrated that the bigel formulation was characterized by higher initial permeability rate providing a fast therapeutic effect with simultaneous moderate retention in mucosal tissue to decrease the risk of local cytotoxicity.

Mucoadhesive gelling systems based on chitosan and chitosan/β-glycerophosphate (β-GP) were developed in order to increase clotrimazole residence time in the vaginal cavity. Ex vivo mucoadhesiveness using porcine vaginal mucosa followed with mechanical, viscoelastic, and swelling properties of prepared hydrogels were evaluated. Drug-free, sterile, unmodified, and β-GP crosslinked chitosan were investigated for the in vitro cytotoxicity in CRL 2616 human vaginal mucosa cells using MTT assay, fluorescent microscopy, and flow cytometry analysis. Chitosan/β-GP hydrogels exhibited pseudoplastic and thixotropic properties. Ionic interaction between β-GP and chitosan improved mechanical properties of hydrogels in terms of hardness, cohesiveness, and compressibility. The hydrogels' ability to interact with porcine vaginal mucosa (measured as force of detachment and work of adhesion) was comparable to those obtained with reference mucoadhesive gel Replens™. Surprisingly, greater mucoadhesive properties were noticed for chitosan/β-GP hydrogels. The cytotoxic effect of unmodified and β-GP crosslinked chitosan was hardly affected by chitosan molecular weight, exhibited mainly through inducing apoptosis, and was found to be significantly lower in the presence of chitosan/β-GP. Furthermore, the higher amount of β-GP was used to crosslink chitosan, the lower cytotoxic effect was observed.

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