The present study reports on the encapsulation of Elsholtzia ciliata ethanolic extract by freeze-drying method using skim milk, sodium caseinate, gum Arabic, maltodextrin, beta-maltodextrin, and resistant-maltodextrin alone or in mixtures of two or four encapsulants. The encapsulation ability of the final mixtures was evaluated based on their microencapsulating efficiency (EE) of total phenolic compounds (TPC) and the physicochemical properties of freeze-dried powders. Results showed that the freeze-dried powders produced using two encapsulants have a lower moisture content, but higher solubility, Carr index, and Hausner ratio than freeze-dried powders produced using only one encapsulant in the formulation. The microencapsulating efficiency of TPC also varied depending on encapsulants used. The lowest EE% of TPC was determined with maltodextrin (21.17%), and the highest with sodium caseinate (83.02%). Scanning electron microscopy revealed that freeze-drying resulted in the formation of different size, irregular shape glassy particles. This study demonstrated good mucoadhesive properties of freeze-dried powders, which could be incorporated in buccal or oral delivery dosage forms. In conclusion, the microencapsulation of E. ciliata ethanolic extract by freeze-drying is an effective method to produce new value-added pharmaceutical or food formulations with polyphenols.

Alginate (ALG) cross-linking by CaCl₂ is a promising strategy to obtain modified-release drug delivery systems with mucoadhesive properties. However, current technologies to produce CaCl₂ cross-linked alginate microparticles possess major disadvantages, such as a poor encapsulation efficiency of water-soluble drugs and a difficulty in controlling the process. Hence, this study presents a novel method that streamlines microparticle production by spray drying; a rapid, continuous, reproducible, and scalable technique enabling obtainment of a product with low moisture content, high drug loading, and a high production yield. To model a freely water-soluble drug, metformin hydrochloride (MF) was selected. It was observed that MF was successfully encapsulated in alginate microparticles cross-linked by CaCl₂ using a one-step drying process. Modification of ALG provided drug release prolongation—particles obtained from 2% ALG cross-linked by 0.1% CaCl₂ with a prolonged MF rate of dissolution of up to 12 h. Cross-linking of the ALG microparticles structure by CaCl₂ decreased the swelling ratio and improved the mucoadhesive properties which were evaluated using porcine stomach mucosa.

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.

Clotrimazole (CLO) is a local imidazolic antifungal agent. A major problem associated with the successful formulation of effective dosage forms containing CLO is its poor aqueous solubility, which presents a hindrance for the local availability of CLO and limits the effective antifungal therapy. In the present study, the effects of various concentrations of poly(amidoamine) (PAMAM) dendrimers generation 2 (G2) and generation 3 (G3) with amine (PAMAM-NH2) or hydroxyl surface groups (PAMAM-OH) on aqueous solubility and antifungal activity of CLO were studied. The obtained results showed that all tested PAMAM dendrimers improved the solubility of CLO and the more potent were PAMAM-NH2 dendrimers. The increase in solubility of CLO was highest at dendrimer concentration of 10 mg/ml. Microbiology studies indicated that only PAMAM-NH2 dendrimers significantly increased the antifungal activity of CLO (a 4—32-fold increase in the antifungal activity compared to pure CLO) and the most potent was dendrimer PAMAM-NH2 G2. These observations indicate that PAMAM dendrimers might be considered as potential carriers of CLO and provide further impetus to evaluate these polymers for use in basic drug delivery studies and to design semisolid dosage forms based on dendrimers with antimicrobial drugs, like CLO.

Sodium alginate is a polymer with unique ability to gel with different cross-linking agents in result of ionic and electrostatic interactions. Chitosan cross-linked alginate provides improvement of swelling and mucoadhesive properties and might be used to design sustained release dosage forms. Therefore, the aim of this research was to develop and evaluate possibility of preparing chitosan cross-linked alginate microparticles containing metformin hydrochloride by the spray-drying method. In addition, influence of cross-linking agent on the properties of microparticles was evaluated. Formulation of microparticles prepared by the spray drying of 2% alginate solution cross-linked by 0.1% chitosan was characterized by good mucoadhesive properties, high drug loading and prolonged metformin hydrochloride release. It was shown that designed microparticles reduced rat glucose blood level, delayed absorption of metformin hydrochloride and provided stable plasma drug concentration. Additionally, histopathological studies of pancreas, liver and kidneys indicated that all prepared microparticles improved degenerative changes in organs of diabetic rats. Moreover, no toxicity effect and no changes in rats behavior after oral administration of chitosan cross-linked alginate microparticles were noted.

Candida species are opportunistic fungi, which are primary causative agents of vulvovaginal candidiasis. The cure of candidiasis is difficult, lengthy, and associated with the fungi resistivity. Therefore, the research for novel active substances and unconventional drug delivery systems providing effective and safe treatment is still an active subject. Microparticles, as multicompartment dosage forms due to larger areas, provide short passage of drug diffusion, which might improve drug therapeutic efficiency. Sodium alginate is a natural polymer from a polysaccharide group, possessing swelling, mucoadhesive, and gelling properties. Gelatin A is a natural high-molecular-weight polypeptide obtained from porcine collagen. The purpose of this study was to prepare microparticles by the spray-drying of alginate/gelatin polyelectrolyte complex mixture, with a novel antifungal drug—luliconazole. In the next stage of research, the effect of gelatin presence on pharmaceutical properties of designed formulations was assessed. Interrelations among polymers were evaluated with thermal analysis and Fourier transform infrared spectroscopy. A valid aspect of this research was the in vitro antifungal activity estimation of designed microparticles using Candida species: C. albicans, C. krusei, and C. parapsilosis. It was shown that the gelatin addition affected the particles size, improved encapsulation efficiency and mucoadhesiveness, and prolonged the drug release. Moreover, gelatin addition to the formulations improved the antifungal effect against Candida species.