Composite nanoparticles based on hyaluronic acid chemically cross-linked with alpha,beta-polyaspartylhydrazide.

In this paper, new composite nanoparticles based on hyaluronic acid (HA) chemically cross-linked with alpha,beta-polyaspartylhydrazide (PAHy) were prepared by the use of a reversed-phase microemulsion technique. HA-PAHy nanoparticles were characterized by FT-IR spectroscopy, confirming the occurrence of the chemical cross-linking, dimensional analysis, and transmission electron micrography, showing a sub-micrometer size and spherical shape. Zeta potential measurements demonstrated the presence of HA on the nanoparticle surface. A remarkable affinity of the obtained nanoparticles toward aqueous media that simulate some biological fluids was found. Stability studies showed the absence of chemical degradation in various media, while in the presence of hyaluronidase, a partial degradation occurred. Cell compatibility was evaluated by performing in vitro assays on human chronic myelogenous leukaemia cells (K-562) chosen as a model cell line and a haemolytic test. HA-PAHy nanoparticles were also able to entrap 5-fluorouracil, chosen as a model drug, and release it in a simulated physiological fluid and in human plasma with a mechanism essentially controlled by a Fickian diffusion.

Preparation and characterization of solid lipid nanoparticles containing cloricromene.

This article describes the development of solid lipid nanoparticles (SLN) as colloidal carriers for cloricromene. Nanoparticles were prepared by the microemulsion or precipitation technique. In vitro drug release profile from SLN was studied under various experimental conditions mimicking some body fluids. The drug release rate of drug at pH 7.4 and human plasma is high. In plasma, after 15 min, about 70% of drug was released. The cloricromene that was not released within 4 hr was found in the SLN. This result suggests that this colloidal system could be useful for targeted drug delivery to the central nervous system after intravenous administration.

Coupling of the antiviral agent zidovudine to polyaspartamide and in vitro drug release studies.

A macromolecular prodrug of the known antiretroviral agent zidovudine and alpha, beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) was synthesized. A succinic spacer was present between the polymer and the drug, and 1,1'-carbonyldiimidazole was used as the coupling agent. In vitro drug release studies at pH 1.1, 5.5 and 7.4 indicated that limited amounts of intact drug were released from the conjugate. At pH 1.1 and 7.4 succinylzidovudine was released, and this was hydrolysed to give free zidovudine. In the presence of alpha-chymotrypsin, zidovudine was released preferentially in comparison with the succinyl derivative. The amounts of released zidovudine and succinylzidovudine were greater in plasma than in aqueous buffer solutions. These results show that after i.v. administration this drug-polymer conjugate can release zidovudine into the blood circulation for prolonged periods.

Preparation, characterization and in vitro antimicrobial activity of ampicillin-loaded polyethylcyanoacrylate nanoparticles.

In this paper, the experimental conditions for preparing ampicillin-loaded polyethylcyanoacrylate (PECA) nanoparticles are described. The effects of drug concentration and surfactant type in the polymerization medium on the particle size distribution and loading capacity were studied. The results of these studies show that only the type of surfactant has an impact on the nanoparticle dimensions. The release rate of ampicillin from PECA nanoparticles at pH 7.4 (extracellular value pH) performed either with and without esterases, show that the drug release is considerably increased in the presence of these exzymes. The results of drug release study at pH 1.1 (simulated gastric juice) are very interesting. This study has evidenced that the 70% of ampicillin is released quickly, while the remaining fraction is firmly incorporated in nanoparticles. The released ampicillin is quickly degraded in acid medium while the entrapped fraction is protected from acid degradation and afterwards, when nanoparticles reach the small intestine, can be readily released in the presence of esterases. This result could be exploited for the oral administration of the ampicillin-PECA system. Finally, studies of antimicrobial activity of prepared systems evidenced that ampicillin-loaded PECA nanoparticles exhibit an activity equal or higher than the free drug.

Evaluation of polyalkylcyanoacrylate nanoparticles as a potential drug carrier: preparation, morphological characterization and loading capacity.

Some physicochemical behaviours were investigated of polyethyl- (PECA) and polyisobutylcyanoacrylate (PICA), which, in recent years, have been proposed as nanoparticle colloidal systems for drug carrying. We observed the influence of preparation conditions, such as pH value and surfactant concentration, on parameters such as particle size and polymer molecular weight. Lower operating pH values (0-2) resulted in smaller nanoparticles than those prepared at pH 5.5. The polymer molecular weight was also a function of pH: low molecular weight at low pH and vice-versa. The surfactant concentration positively influenced main particle size and polymer molecular weight. These trends were independent of type of monomer; in fact, both ethyl- (ECA) and isobutyl-2-cyanoacrylate (ICA) showed the same behaviour. Loading capacity, as well as release profile, of the two polymers were evaluated using fluorescein as a model drug. Whereas both polymers showed almost the same release profile, there was a difference in the amount of encapsulated probe: higher aliquots for PICA than for PECA. Storage effects on such physicochemical parameters were also tested.

Synthesis of macromolecular prodrugs of procaine, histamine and isoniazid.

The attachment of various drugs bearing -NH2 groups to poly-alpha,beta-aspartic acid as a biodegradable carrier afforded in good yields macromolecular prodrugs which were characterized with respect to composition and drug load by spectroscopic and analytical methods. N-Ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) in an aqueous medium proved to be useful in the attachment reaction. Isoniazid, procaine and histamine were covalently coupled as pendant groups onto poly-alpha,beta-aspartic acid via an amide bond. In principle, controlled release of the aforementioned drugs can be achieved by biodegradation of the polymer or by cleavage of covalently bound polymer-drug conjugates.

Synthesis of polymeric derivatives of isoniazid: characterization and in vitro release from a water-soluble adduct with polysuccinimide.

Coupling of isoniazid with polysuccinimide afforded a water-insoluble polymeric pro-drug; by reaction with ethanolamine it was chemically transformed in a water-soluble adduct. The in vitro release of isoniazid from the drug-polymer adduct was studied by using an artificial stomach wall lipid membrane. The transfer rate constant from simulated gastric juice to simulated plasma was defined and compared with that of an equivalent dose of pure drug.

[Carrier polymers. Synthesis of a new multiaspartic hydrazide]. / Polimeri 'carrier'. Sintesi di una nuova poliaspartidrazide [corrected].

Synthesis of a new polyasparthydrazide obtained from the reaction of polysuccinimide with hydrazine is described. The new polymer is water soluble. Moreover, the presence of - NH2 groups allowed the reaction with drugs bearing certain functional groups. Therefore polyasparthydrazide seems to be a very interesting candidate as a drug carrier.