Marianne Hiorth

Stability of chitosan nanoparticles cross-linked with tripolyphosphate.

The physical stability of chitosan nanoparticles cross-linked with sodium tripolyphosphate (TPP) was investigated over a period of 1 month. Special emphasis was placed on changes in the particle size and the particle compactness, which are two important physicochemical parameters of nanoparticulate drug delivery systems. The chitosan-TPP particles were prepared at different ionic strengths, chitosan chloride concentrations, and TPP-to-chitosan ratios. In the presence of monovalent salt, the positive ζ potential of the particles was reduced. In spite of this, the particles were more stable when prepared and stored under saline conditions compared to water. This could be attributed to the smaller particle sizes found in the presence of sodium chloride. Most of the particles prepared in saline solvents were stable with respect to changes in the size and the compactness of the particles. However, instability was observed at the highest cross-linker-to-polymer ratios. Generally, a reduction in the ζ potential and an increase in the particle compactness were observed at increasing TPP-to-chitosan ratios. This combined with the size increase induced by a high concentration of chitosan, increased the aggregation and sedimentation tendency of the particles and reduced the colloidal stability of the particles.

Effects of ionic strength on the size and compactness of chitosan nanoparticles

In this work, chitosan nanoparticles were prepared by ionotropic gelation of chitosan with tripolyphosphate (TPP). The effects of the ionic strength of the solvent employed in the particle preparation on the average size and compactness of the particles were investigated. In addition, the effects of the chitosan concentration and the crosslinker to polymer ratio on the particle characteristics were studied. The chitosan–TPP nanoparticles were characterized by dynamic light scattering, zeta potential, and turbidity measurements. The compactness of the nanoparticles was estimated with a method based on the size of the nanoparticles and the turbidity of the nanoparticle suspension. All the investigated preparation parameters, i.e., the ionic strength of the solvent, the chitosan concentration, and the TPP to chitosan ratio, affected the particle characteristics. For instance, smaller and more compact particles were formed in saline solvents, compared to particles formed in pure water. Further, the addition of monovalent salt rendered it possible to prepare particles in the nanometer size range at a higher polymer concentration. Solvent salinity is thus an important parameter to address in the preparation of chitosan nanoparticles crosslinked with TPP.

Studies on pectin coating of liposomes for drug delivery

The present study investigated the surface coating of charged liposomes by three different types of pectin (LM, HM and amidated pectin) by particle size determinations and zeta potential measurements. The pectins and the pectin coated liposomes were visualized by atomic force microscopy. The adsorption of pectin onto positive liposomes yielded a reproducible increase in particle size and a shift of the zeta potential from positive to negative side for all three pectin types, whereas the adsorption of pectin onto negative liposomes did not render any significant changes probably due to electrostatic repulsion. The positive liposomes coated with HM-pectin gave the largest pectin coated particles with the least negative zeta potential, while the opposite was observed for the LM-pectin coated positive liposomes. Furthermore, results from dynamic light scattering revealed narrow size distributions, indicating that the degree of aggregation was low for the pectin coated liposomes. As liposomes are able to encapsulate drugs and pectin has been found to be mucoadhesive, these pectin coated liposomes may be potential drug delivery systems.

The potential of pectin as a stabilizer for liposomal drug delivery systems

The aim of the present study was to investigate the potential of different types of pectin as stabilizers for liposomal drug delivery systems. Positively charged liposomes were coated with commercially available and purified low-methoxylated (LM), high-methoxylated (HM) and amidated (AM) pectins. The samples were stored for up to 12 weeks at 4°C, at room temperature and at 35°C. The change in liposomal size and size distribution, zeta potential, pH, leakage of encapsulated carboxyfluorescein (CF), and lipid degradation were studied. All the types of pectin were found to protect the liposomes against aggregation during storage. The pectin coat did not affect the permeability of the liposome membrane. HM and LM pectin seemed to be the most promising types of pectin due to minimal changes in the zeta potentials during storage for these samples and no detectable lipid degradation. It is concluded that pectin may be used for stabilizing liposomal drug delivery systems.

The formation and permeability of drugs across free pectin and chitosan films prepared by a spraying method

This study has investigated the permeation of drugs through free films made of pectin and chitosan. The background for this study is the intended use of the films as coating material in a colon-specific drug delivery device. The factors that varied when making the films were the pectin source and grade of the pectin, degree of deacetylation of the chitosan and ratio between pectin and chitosan. The permeability of the model drug in 0.1 M HCl was low with an average drug release of 1.3 x 10(-3)%/cm. The films containing high content of chitosan showed exponential kinetics while the films containing high content of pectin showed 0-order kinetics. The release of drug in phosphate buffer pH 6.8 showed 0-order kinetics. The lowest permeability was obtained for a film consisting of a high content of pectin to chitosan, chitosan with a high degree of deacetylation and non-amidated low methoxylated citrus pectin. The permeation of paracetamol for this combination was 9.4 x 10(3)%/cm. This film combination had a combined diffusion of only 0.046%/cm after 1 h in 0.1 M HCl and 4 h in phosphate buffer pH 6.8.

Mucoadhesion and drug permeability of free mixed films of pectin and chitosan: an in vitro and ex vivo study.

The objective of this study was to identify the important factors for the drug permeability and mucoadhesion of casted free pectin/chitosan combination films. The factors varied were: the type of pectin (low and high methoxyl pectin) and the ratio pectin:chitosan (25:75, 50:50 and 75:25). The model drug used for measuring drug permeability was paracetamol. A texture analyzer was used for measuring mucoadhesion by using two different setups: (1) in vitro tensile tests measuring the detachment force of films versus a mucin dispersion and (2) ex vivo shear tests measuring the friction forces between pre-hydrated films and fresh porcine small intestine, with the system immersed in phosphate buffer, pH 6.8. The type of pectin used in the combination films did not have a significant effect on the drug permeability. The ex vivo mucoadhesion test revealed significant differences between low and high methoxyl pectin only for the 50:50 pectin:chitosan films. For that type of film, the peak and friction forces were highest for high methoxyl pectin. Both the mucoadhesion and drug permeability generally increased with decreasing amounts of pectin relative to chitosan in the films.

Studies on pectin-coated liposomes and their interaction with mucin

Pectin is a polymer with well-known mucoadhesive properties. In this study, liposomes were coated with three different types of pectin. Their properties were characterized and their mucoadhesiveness was estimated by a novel in vitro approach. Two different types of commercially available mucin were investigated in order to choose the best candidate for the method. The effect of pH on the properties of the coated liposomes and the interaction with mucin was also studied. The pectin-coated liposomes and the complexes they formed with mucin were characterized by dynamic light scattering (DLS), zeta potential and turbidity measurements. The zeta potential of the liposomes shifted from positive to negative after coating with pectin. They also exhibited larger diameters, and the liposomes coated with HM-pectin were the largest. After the addition of mucin, the zeta potential shifted to a less negative value and the sizes of the pectin-coated liposomes increased. The complexes formed between mucin and the HM-pectin-coated liposomes were the largest, while the smallest were formed with the LM-pectin-coated liposomes. The pH was found to affect the interaction between the coated liposomes and mucin. DLS was conducted on an ALV goniometer to gain information about the diffusivity of the samples, the relative scattered intensities and to obtain an optimal characterization of the size distributions. The results correlated well with measurements from an automatized light scattering instrument (Zetasizer Nano ZS).

Preparation of ionically cross-linked pectin nanoparticles in the presence of chlorides of divalent and monovalent cations.

Nanoparticles were prepared by ionotropic gelation of low-methoxylated (LM) and amidated low-methoxylated (AM) pectin with zinc chloride (ZnCl2) in aqueous media. The samples were characterized by atomic force microscopy, dynamic light scattering, turbidimetry, zeta potential, and pH measurements. Pectin nanoparticles could be prepared at a pectin concentration of 0.07% (w/w) and a ZnCl2-to-pectin ratio of 15:85 (w/w) in the presence of sodium chloride, but not in pure water. Interestingly, particles in the nanometer size-range could also be prepared in the absence of the cross-linker ZnCl2. The dynamic light scattering studies revealed that the AM-pectin nanoparticles were much less polydisperse than the LM-pectin nanoparticles. The AM-pectin nanoparticles were therefore considered to be more promising as a potential drug delivery system, and further studies were performed to investigate the colloidal stability and the effect of the pectin concentration on the size, charge, and compactness of these nanoparticles.

Advanced drug delivery systems for local treatment of the oral cavity

Good oral health is of major importance for general health and well-being. Several innovative drug delivery systems have been developed for the local treatment and prevention of various diseases in the oral cavity. However, there are currently few optimal systems and many therapeutic challenges still remain, including low drug efficacy and retention at targeted site of action. The present review provides an insight into the latest drug delivery strategies for the local treatment and prevention of the four most common oral pathologies, namely, dental caries, periodontitis, oral mucosal infections and oral cancer. The potential of bioadhesive formulations, nanoparticulate platforms, multifunctional systems and photodynamic methodologies to improve therapy and prophylaxis in future local applications for the oral cavity will be discussed.

The potential of liposomes as dental drug delivery systems.

The potential of liposomes as a drug delivery system for use in the oral cavity has been investigated. Specifically targeting for the teeth, the in vitro adsorption of charged liposomal formulations to hydroxyapatite (HA), a common model substance for the dental enamel, has been conducted. The experiments were performed in human parotid saliva to simulate oral-like conditions. It was observed, however, that precipitation occurred in tubes containing DPPC/DPTAP or DPPC/DPPG-liposomes in parotid saliva with no HA present, indicating that constituents of parotid saliva reacted with the liposomes. The aggregation reactions of liposome-parotid saliva mixtures were examined by turbidimetry and by atomic force microscopy. Negatively charged DPPC/DPPS and DPPC/PI-liposomes were additionally included in these experiments. The initial turbidity of positive DPPC/DPTAP-liposomes in parotid saliva was very high, but decreased markedly after 30 min. AFM images showed large aggregates of micelle-like globules known to be present in saliva. The turbidity of the various negatively charged liposome and parotid saliva mixtures stayed relatively constant throughout the measuring time; however, their initial turbidities were different; mixtures with DPPC/DPPG-liposomes were the most turbid and DPPC/DPPA-liposomes the least. Pyrophosphate (PP) was added to the various liposome-parotid saliva mixtures to examine the effect of Ca(2+) on the interactions. The effect of PP treatment of the negatively charged liposome-parotid saliva mixtures was most pronounced with DPPC/DPPG-liposome mixtures where it caused a sudden drop in turbidity. For positive DPPC/DPTAP liposome and parotid saliva mixtures, the effect of PP was minimal. These experiments showed that saliva constituents may interact with liposomes. An appropriate liposomal drug delivery system intended for use in the oral cavity seems to be dependent on the liposomal formulation. Based on the present results, negatively charged DPPC/DPPA-liposomes seem to be most suitable for use in the oral cavity as they were found to be the least reactive with the components of parotid saliva.