1,695 research outputs found
Effects of chitosan derivatives (DChH1, DChL1, DchL2) on the proliferation and cytoskeleton of human fibroblasts ¿in vitro¿.
No full textStrategies to prolong the residence time of drug delivery systems on ocular surface
No full textOcular diseases may be treated via different routes of administration, such as topical, intracameral, intravitreal, oral and parenteral. Among them the topical route is most accepted by patients, although it provides in many cases the lowest bioavailability. Indeed, when a topical formulation reaches the precorneal area, i.e., the drug absorption and/or action site, it is rapidly eliminated due to eye protection mechanisms such as blinking, basal and reflex tearing, and naso-lacrimal draining. To avoid this and to reduce the frequency of dosing, various strategies have been developed to prolong drug residence time after topical administration. These strategies include the use of viscosity increasing and mucoadhesive excipients as well as combinations thereof. From the drug delivery system point of view, liquid and semisolid formulations are preferred over solid formulations such as ocular inserts and contact lenses. Furthermore, liquid and semisolid formulations can contain nano- and microcarrier systems that contribute to a prolonged residence time. Within this review an overview about the different types of excipients and formulations as well as their performance in valid animal models and clinical trials is provided
Impact of mucoadhesive polymeric nanoparticulate systems on oral bioavailability of a protein model drug
No full textRokitamycin loaded microparticles based on chitosan for the therapy of amoebic infections.
No full textOBJECTIVES
The aims of this study were: i) to assess the
feasibility of using biodegradable chitosan
microspheres as carriers for controlled release of
rokitamycin (RK), able to improve the antiamoebic
activity of the drug;i ii) to investigate the preparative
parameters for obtaining microspheres based on
chitosan (CH) suitable for ocular or nasal
administration of rokitamycin;ii iii) to verify if it was
possible to maintain microsphere characteristics
suitable for ocular or nasal administration using water
soluble polymers such as new chitosan derivatives,
diethylaminomethyl-(diethyldimethylene ammonium)n
methylchitosans (C7 and C8) or CH salt, chitosan
glutamate (CG);ii iv) to evaluate the influence of
chitosan properties (CH vs CG) on the in vivo
rokitamycin absorption, after nasal administration of
spray dried microspheres.iii
METHODS
Preparation of spray dried microspheres.
Microsphere formulations based on CH or C7 or C8 or
CG were prepared by spray drying (Mini Büchi B-191,
Büchi Laboratoriums-Technik AG, Flawil,
Switzerland) using different drug–polymer ratios (1–3
and 1–4) and starting from feed solutions with diverse
concentrations (1.5%, 1%, 0.5% and 0.25% (w/v)).
Characterisation of Microspheres. Microparticles
prepared were characterised in terms of yield of
production, drug loading and encapsulation efficiency,
particle size, morphology, in vitro drug release, water
uptake, in vitro mucoadhesion, ex vivo drug
permeation, Energy Dispersive X-ray Diffraction
(EDXD) measurements.
Determination of effects of drug and microspheres
on Acanthamoeba growth. Loaded and unloaded CH
microspheres were dispersed in PYG medium and
applied on trophozoite grown in sterile 24-well plates
(Corning). At selected time intervals (3, 4, 7, 9 and 15
days of incubation), amoebas growing in each well
were counted in a Nageotte chamber, using the inverted
microscope.
In vivo RK administration. Nasal administration of
CG and CH microparticles containing RK to each
nostril of the anaesthetized Male Wistar rats was
performed by use of single dose Monopowder P®
insufflators (Valois Dispray). At predetermined times,
blood and liquor samples were collected and analyzed.
Results were compared with those obtained after
intravenous infusion of RK and nasal administration of
RK aqueous suspension.
CONCLUSIONS
The loading of RK into CH microspheres improves
and prolongs the in vitro antiamoebic activity of the
drug.i CH based microspheres with good morphology
and narrow size distribution, able to increase the
dissolution rate of RK, can be obtained by spray drying
using a low concentration of feed solution and 1-4
drug–polymer ratio.ii RK encapsulation into CH
microspheres increases its poor ex vivo permeability
through nasal sheep mucosa. The encapsulation of RK
in C7 and C8 by using the chosen parameters results in
microparticles showing similar or often better
properties than formulations made by CH with respect
to size, in vitro release behaviour and
mucoadhesiveness.ii
Compared with CH particles, CG microspheres
load the drug in amorphous form, leading to the best
improvement of its water solubility. This property, as
well as the rapid water uptake of CG particles,
increases more the release rate of the drug from
microspheres and only after their in vivo nasal
administration, RK goes to the cerebrospinal fluid and
the bloodstream.iii
ACKNOWLEDGEMENTS
This work was supported by MiUR through grant
PRIN05 and Fondazione Banco di Sardegna. The
authors thank “Farmaceutici Formenti S.p.A” and
Valois Pharma for the donation of RK and the powder
insufflators, respectively.
REFERENCES
i Rassu, G., Gavini, E., Mattana, A., Giunchedi, P. Open
Drug Del J, 2, 38-43, 2008.
ii Rassu, G., Gavini, E., Jonassen, H., Zambito, Y., Fogli, S.,
Breschi, MC, Giunchedi, P. J. Pharm. Sci., 98, 4852-4865,
2009.
iii Gavini, E., Rassu, G., Ferraro, L., Generosi, A., Rau, JV.,
Brunetti, A., Giunchedi, P., Dalpiaz, A. J. Pharm. Sci., In
Press
Bergamot Essential Oil: A Method for Introducing It in Solid Dosage Forms
No full textBergamot essential oil (BEO) possess antimicrobial, antiproliferative, anti-inflammatory, analgesic, neuroprotective, and cardiovascular effects. However, it is rich in volatile compounds, e.g., limonene, that are susceptible to conversion and degradation reactions. The aim of this communication was to prepare a conjugate based on a quaternary ammonium chitosan derivative (QA-Ch) and methyl-βCD (MCD), coded as BEO/QA-Ch-MCD, to encapsulate BEO in order to stabilize its volatile compounds, eliminate its unpleasant taste, and convert the oil in a solid dosage form. The obtained conjugate, BEO/QA-Ch-MCD, was highly soluble and had a percentage of extract association efficiency (AE %), in terms of polyphenols and limonene contents, of 22.0 ± 0.9 and 21.9 ± 1.2, respectively. Moreover, stability studies under UV stress in simulated gastric fluid showed that BEO/QA-Ch-MCD was more able to protect polyphenols and limonene from degradation compared to free BEO or BEO complexed with MCD (BEO/MCD). The complexation and subsequent lyophilization allowed the transformation of a liquid into a solid dosage form capable of eliminating the unpleasant taste of the orally administered oil and rendering the solid suitable to produce powders, granules, tablets, etc. These solid oral dosage forms, as they come into contact with physiological fluids, could generate nanosized agglomerates able to increase the stability of their active contents and, consequently, their bioavailability
Dexamethasone drug delivery systems based on a mucohadesive water soluble chitosan-MCD conjugate
No full textGELLAN GUM MICROPARTICLES FOR INTESTINE-TARGETED DELIVERY OF PROBIOTICS
No full textThis study focuses on developing carriers for probiotic formulations to create innovative functional foods. Among biobased polymers, gellan gum was chosen for encapsulating probiotic microorganisms due to its widespread use as a gelling agent in various foods and as an agar substitute for microbiological plate assays. Additionally, gellan gum microparticles have demonstrated cryoprotective and gastroretentive properties.
Lactobacillus Fermentum was used as model probiotic for this work. Gellan gum microparticles were produced by electrohydrodinamic microdripping. Gellan gum powder was disselved in distilled water at different concentrations (0.5, 1, 1.25 %wt) by stirring at 90°C. Solutions were autoclaved and pumped throug a stainless steel needle (positive high voltage). Microparticles were directly collected in 20 mL of 1%wt CaCl2 crosslinking bath (grounded). L. Fermentum was inoculated in De Man, Rogosa and Sharpe (MRS) broth and plated on MRS agar to determine colony-forming units (CFU). Bacterial suspensions were prepared determining OD600, centrifuged and resuspended in 1% wt gellan gum (GG1), to achieve probiotic loads of 106 CFU/mL (GG1-low) and 109 CFU/mL (GG1-high). GG1-low was re-incubated in MRS broth for 24 and 48h, and stained with Syto9 fluorescent dye to assess bacterial growth inside the particles.
A 1% wt gellan gum solution was identified and tested for probiotic entrapment. Wet particle size distributions were systematically studied at an optimized flow rate (1 mL/h) and voltage (25 kV) to evaluate the effect of probiotic inclusion. Empty particles had a mean size of 250 ± 50 μm, while GG1-low (106 CFU/mL) and GG1-high (109 CFU/mL) had sizes of 300 ± 40 μm and 450 ± 100 μm, respectively. Plating of the particles showed high probiotic viability post-encapsulation. Plating of the crosslinking bath after filtration displayed at least 2-log units less CFU with respect the dripped ones, indicating high encapsulation efficiency.
The obtained particles exhibited a size range suitable for the food industry, and various concentrations of microorganisms were successfully trapped inside the hydrogel matrix. Re-incubation of GG1-low and Syto9 staining demonstrated the ability of probiotics to grow both inside and on the surface of the particles. Overall, the tested processes proved effective for directly encapsulating high probiotic loads and regrowing probiotics within the particles. The latter method may potentially be utilized to produce particles containing both high loads of probiotics and postbiotics in a single formulation
Binding and mucoadhesion of sulfurated derivatives of quaternary ammonium-chitosans and their nanoaggregates: An NMR investigation
No full textThe effect of insertion of SH and S-protected groups on the binding and mucoadhesion properties of quaternary ammonium-chitosans and their nanoparticulate forms has been investigated by NMR spectroscopy. Diclofenac sodium salt has been assumed as low molecular weight probe to detect the different binding behaviour of polymeric materials; mucin from bovine submaxillary glands was selected as the model protein for differentiating their mucoadhesion. NMR proton selective relaxation rates of the probe molecule were remarkably sensitive to the presence of very low amounts of sulfurated moieties. Impact of supramolecular aggregation in nanostructured species was demonstrated as well as the relevance of S-protection
Quaternary ammonium chitosans: The importance of the positive fixed charge of the drug delivery systems
No full textAs a natural polysaccharide, chitosan has good biocompatibility, biodegradability and biosecurity. The hydroxyl and amino groups present in its structure make it an extremely versatile and chemically modifiable material. In recent years, various synthetic strategies have been used to modify chitosan, mainly to solve the problem of its insolubility in neutral physiological fluids. Thus, derivatives with negative or positive fixed charge were synthesized and used to prepare innovative drug delivery systems. Positively charged conjugates showed improved properties compared to unmodified chitosan. In this review the main quaternary ammonium derivatives of chitosan will be considered, their preparation and their applications will be described to evaluate the impact of the positive fixed charge on the improvement of the properties of the drug delivery systems based on these polymers. Furthermore, the performances of the proposed systems resulting from in vitro and ex vivo experiments will be taken into consideration, with particular attention to cytotoxicity of systems, and their ability to promote drug absorption
Rokitamycin loaded microparticles based on chitosans for the therapy of amoebic infections
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