Biomedical subjects

Maria Cristina Bonferoni

Publications and source records attributed to Maria Cristina Bonferoni.

9 recordsLinked to original sources

PubMed2006

Nanoparticles based on N-trimethylchitosan: evaluation of absorption properties using in vitro (Caco-2 cells) and ex vivo (excised rat jejunum) models.

Among the chitosan derivatives, trimethylchitosan (TMC) has been shown to have penetration enhancement properties also in intestinal environment. In addition, the use of nanoparticulate systems has the advantage of protecting peptidic drugs from intestinal degradations, due to internalisation behaviour. Therefore, the aim of this paper was to evaluate nanoparticulate systems based on TMC. In particular the mucoadhesive and absorption enhancement properties of nanoparticles based on TMC with different quaternization degree (QD) intended for the intestinal administration of macromolecules (peptides) have been evaluated. Comparison with chitosan (CS.HCl) nanoparticles was made. The nanoparticles were loaded with fluorescein isothiocyanate dextran (FD4, MW 4400 Da), used as the model macromolecule. The intestinal penetration enhancement properties of nanoparticles were investigated in an in vitro Caco-2 cell model and an ex vivo rat jejunum model. The mucoadhesion of the nanosystems was evaluated using excised rat jejunum. All of the nanoparticulate systems interacted with the Caco-2 cells decreasing the transepithelial electric resistance (TEER) and increasing Lucifer Yellow (LY) Papp (paracellular pathway marker). All the nanosystems improved FD4 Papp, with the exception of the nanoparticles based on TMC with the highest QD. In this case an entrapment of nanoparticles into Caco-2 cells was supposed. Analogous results were obtained using the excised rat jejunum model. The increase in QD of TMC was seen to favour the mucoadhesion, resulting in a prolonged residence time on intestinal mucosa. The nanoparticle penetration into excised rat jejunum tissue, observed by means of CLSM, suggested that the mucoadhesive properties delayed the absorption of nanoparticles, however they produced an increase in the contact time with intestinal epithelium, offering a better chance for internalisation. The improvement of mucoadhesion and of nanoparticle internalisation with respect to chitosan nanosystems makes the TMCs nanosystems suitable carriers for the intestinal absorption of peptides.

Adhesiveness↗

PubMed2005

Ophthalmic delivery systems based on drug-polymer-polymer ionic ternary interaction: in vitro and in vivo characterization.

Aim of the work was to develop mucoadhesive eyedrops containing tetrahydrozoline hydrochloride (TZ), a decongestant drug, and based on a ternary interaction drug-polymer-polymer. The anionic polymers assessed were the anionic hyaluronic acid (HA) and polyacrylic acid (PAA), the cationic chitosan (HCS) and the polyelectrolyte gelatin (G). Formulations based on the ternary systems TZ/G/HA, TZ/HCS/HA, TZ/G/PAA and TZ/HCS/PAA at the stoichiometry ratios between cationic and anionic polymers and containing a 10 and 20 fold excess of the anionic polymers were prepared. The formulations were characterized for in vitro mucoadhesive and release properties. The ex vivo/in vivo residence properties were assessed for the formulations that combined the better in vitro mucoadhesive and release properties. The physical stability of the formulations selected was determined following steam sterilization and storage at 25 and 40 degrees C. The synergistic effect of G with HA and PAA improves the mucoadhesion of the formulations while the interaction of HCS with HA and PAA is likely to produce higher neutralization of the anionic polymer charge and minor chain flexibility resulting in a limited mucoadhesion improvement. Both G and HCS participate to control drug release. The selected formulations demonstrate to possess consistency (viscosity) sensitive to the ions of the medium, and probably for this reason the ex vivo/in vivo residence properties could not directly correlated to mucoadhesion and to drug release control properties. However, the formulations are able to maintain levels of TZ detectable until 20 min after the instillation in rabbits, while TZ was not detectable since 3 min after instillation of the drug solution. The physical stability, following steam sterilization and storage, the low viscosity combined with good residence time in conjunctival sac make the TZ/G/20HA the more promising formulation.

Acrylic Resins↗

PubMed2005

Buccal penetration enhancement properties of N-trimethyl chitosan: Influence of quaternization degree on absorption of a high molecular weight molecule.

The aim was to evaluate the influence of the degree of quaternization of N-trimethyl chitosans (TMCs) on the mucoadhesive and penetration enhancement properties towards buccal mucosa. Fluorescein isothiocyanate dextran (MW 4400 Da) (FD4) was used as model molecule. TMCs, obtained from chitosans of different MW (1460 and 580 kDa, respectively), were hydrated in distilled water and in pH 6.4 phosphate buffer (simulating the buccal fluid). The polymer solutions were subjected to mucoadhesion measurements towards bovine submaxillary mucin dispersion and porcine buccal mucosa and to FD4 permeation tests through porcine cheek epithelium. The trimethylation of chitosan allows maintenance or improvement of the mucoadhesive properties of the starting chitosans dependently on quaternization degree. In particular, the mucoadhesive properties increase on increasing degree of quaternization. The trimethylation does not produce any change in chitosan penetration enhancement properties when the medium is distilled water while if pH 6.4 buffer is used, the trimethylation produces an improvement in chitosan penetration enhancing effect. TMC derived from the lower MW chitosan and characterized by the highest degree of quaternization shows the best mucoadhesive and penetration enhancement properties and is the most promising TMC to improve the bioavailability of hydrophilic and large MW molecules (like peptides and proteins) when administered via buccal route.

Absorption↗

PubMed2004

Carrageenan-gelatin mucoadhesive systems for ion-exchange based ophthalmic delivery: in vitro and preliminary in vivo studies.

Lambda-carrageenan is an anionic polymer able to ionically interact with alkaline drugs. This results in a complex that releases the drug slowly, due to displacement by the counterions of the release medium. The aim of this work was to assess the possible ophthalmic employment of such a complex. As a model drug, an alkaline anti-glaucoma drug, timolol maleate, was chosen. Systems in which lambda-carrageenan interacted both with the drug and a mucoadhesive polymer such as gelatin were studied. The combination of carrageenan and gelatin in different ratios proved to be useful in modulating the drug release profiles, the rheological properties of the hydrated formulations and their mucoadhesive properties. Both films and microspheres were prepared and tested in vitro. A microsphere formulation was also tested in vivo in albino rabbits. The drug concentration and bioavailability in the aqueous humour were significantly high in comparison with commercial formulations.

Adhesives↗

PubMed2004

Assessment of chitosan derivatives as buccal and vaginal penetration enhancers.

The aim of the present work was to evaluate the mucoadhesive and penetration enhancement properties via the buccal and vaginal mucosae of four different chitosan derivatives: 5-methyl-pyrrolidinone chitosan (MPC), two low molecular weight chitosans (DC1 and DC2) and a partially reacetylated chitosan (RC). Chitosan HCl was used as a reference. Polymer solutions (4% w/w) were prepared in media simulating the buccal (pH 6.4 buffer or water) and the vaginal (pH 5.0 buffer) environments and subjected to rheological characterization. Acyclovir was added to the polymer solutions at 5% (w/w) concentration. The mucoadhesive properties of the polymer solutions were measured using excised porcine cheek or vaginal mucosa and mucin dispersions to simulate the buccal or vaginal environments, respectively. Drug permeation and penetration tests were carried out using porcine cheek and vaginal mucosae as model membranes. Acyclovir aqueous suspensions prepared in pH 6.4 and 5.0 buffers were used as blanks. Drug release measurements were also carried out in the same conditions employed for the permeation and penetration tests. Methyl-pyrrolidinone chitosan shows the best mucoadhesive and penetration enhancement properties in both buccal and vaginal environments. The capability to enhance the permeation/penetration of acyclovir was decreased by partial depolymerization of chitosan and disappeared after partial reacetylation.

Acyclovir↗

PubMed2004

Mucoadhesive and penetration enhancement properties of three grades of hyaluronic acid using porcine buccal and vaginal tissue, Caco-2 cell lines, and rat jejunum.

The influence of the molecular weight on mucoadhesive and penetration enhancement properties of three grades of hyaluronic acid (1878, 693 and 202 kDa) has been evaluated. The mucoadhesive properties were investigated using buccal and vaginal porcine mucosa by means of a tensile stress method and using rat jejunum by means of an inclined plane method. The mucoadhesive performances observed using animal tissues were compared with the mucoadhesive properties observed using submaxillary or gastric mucin dispersions. The penetration enhancement properties were investigated using porcine buccal epithelium membrane or vaginal tissue and a cell monolayer (Caco-2 cell line). Chitosan hydrochloride, already described as a penetration enhancer towards buccal and vaginal mucosae and Caco-2 cell monolayers, was used as reference. Aciclovir (acyclovir), a poorly soluble and absorbable drug, commonly used in the treatment of Herpes simplex virus (type I and II), was used as the model drug. Unlike chitosan hydrochloride, which does not show any mucoadhesive potential at pH close to neutrality (buccal and intestinal), all hyaluronic acid grades show mucoadhesive properties in all the environments considered (buccal, vaginal and intestinal). In all cases, a decrease in molecular weight of hyaluronic acid produced an increase in the mucoadhesive performance. The hyaluronic acid with the lowest molecular weight (202 kD) exhibited the best penetration enhancement properties, that, depending on the substrate under consideration, was either comparable with or even better than chitosan hydrochloride. Therefore, this grade would be the most promising for buccal, vaginal and intestinal delivery of aciclovir.

Adhesives↗

PubMed2003

Buccal delivery of acyclovir from films based on chitosan and polyacrylic acid.

The aim of the present work was to investigate the possibility of achieving buccal delivery of a problematic drug, acyclovir, from films based on chitosan hydrochloride (HCS) and polyacrylic acid sodium salt (PAA). At first, the ionic interaction between HCS and PAA in distilled water was investigated by means of rheological and turbidimetric analysis. Films containing 1 mg/cm2 of acyclovir and based on pure HCS and on HCS and PAA mixed in different ratios were prepared by casting technique. The films were subjected to hydration, rheological, mucoadhesion, drug release, "wash away," and permeation/penetration measurements. A commercial cream containing acyclovir and an aqueousacyclovir suspension were used as references. The addition of PAA to HCS produced a decrease in film hydration. Films based on HCS/PAA weight ratio close to interaction productstoichiometry were characterized by higher rigidity and better "wash away" properties with respect to the other films and the reference formulation. The worst mucoadhesive properties were shown by films based on mixing ratios close to interaction product stoichiometry. The addition of PAA to HCS produced a lowering in drug release profile. All the films examined promoted the permeation of acyclovir across porcine cheek epithelium when compared with acyclovir suspension and the commercial cream. The penetration enhancement properties were affected by the mixing ratio of the two polymers. The film based on 1/1.3 HCS/PAA weight ratio, besides possessing the best resilience properties on the mucosa, was also characterized by the highest permeation profile and, therefore, represents a promising formulation for buccal delivery of acyclovir.

Absorption↗

PubMed2002

Mucoadhesive vaginal tablets as veterinary delivery system for the controlled release of an antimicrobial drug, acriflavine.

The aim of the study was the development of mucoadhesive vaginal tablets designed for the local controlled release of acriflavine, an antimicrobial drug used as a model. The tablets were prepared using drug-loaded chitosan microspheres and additional excipients (methylcellulose, sodium alginate, sodium carboxymethylcellulose, or Carbopol 974). The microspheres were prepared by a spray-drying method, using the drug to polymer weight ratios 1:1 and 1:2 and were characterized in terms of morphology, encapsulation efficiency, and in vitro release behavior, as MIC (Minimum Inhibitory Concentration), MBC (Minimum Bacterial Concentration), and killing time (KT). The tablets were prepared by direct compression, characterized by in vitro drug release and in vitro mucoadhesive tests. The microparticles have sizes of 4 to 12 microm; the mean encapsulation yields are about 90%. Acriflavine, encapsulated into the polymer, maintains its antibacterial activity; killing time of the encapsulated drug is similar to that of the free drug. In vitro release profiles of tablets show differences depending on the excipient used. In particular Carbopol 974, which is highly cross-linked, is able to determine a drug-controlled release from the matrix tablets for more than 8 hours. The in vitro adhesion tests, carried out on the same formulation, show a good adhesive behavior. The formulation containing microspheres with drug to polymer weight ratios of 1:1 and Carbopol 974 is characterized by the best release behavior and shows good mucoadhesive properties. These preliminary data indicate that this formulation can be proposed as a mucoadhesive vaginal delivery system for the controlled release of acriflavine.

Acriflavine↗

PubMed2002

Influence of complex solubility on formulations based on lambda carrageenan and basic drugs.

The purpose of the present work was to compare the behavior of some drug/carrageenan complexes having different solubility in water, in a controlled release formulation. Diltiazem HCl, bupropion HCl, metoprolol tartrate, and tramadol HCl were used as model drugs. The complexes were characterized by means of solubility measurements, release test at constant surface area, and water uptake measurements, and the results were related to their performance in controlled release formulations. For the more soluble complexes (involving metoprolol and tramadol) the occurrence of gelation after hydration was observed, while diltiazem complex apparently did not gellify; bupropion behavior was intermediate. A correspondence was found between the observed differences in complex solubility and hydration-gelation behavior and the drug release profiles. For all the drugs considered, the release was completed in about 10 to 12 hours, but different kinetics were observed depending on the solubility of the complexes. All the considered complexes seem suitable for controlled release purposes, although the data obtained show the relevance of the complex solubility to drug release profiles.

Buffers↗