Asteria Luzardo-Álvarez

Iontophoretic delivery of ropinirole hydrochloride:effect of current density and vehicle formulation

AbstractPurpose. The objectives of this work were 1) to establish the feasibility of the transdermal iontophoretic delivery of ropinirole hydrochloride; 2) to investigate the possibility of delivering therapeutic doses of this drug; and 3) to determine the key factors that control ropinirole electrotransport. Methods. A series of in vitro transdermal iontophoretic experiments were instituted to study the effects of drug concentration, co-ion concentration, intensity of current, and application time on ropinirole flux. The convective contribution to ropinirole electrotransport was evaluated by following the transport of the electroosmotic marker mannitol. Results. Ropinirole flux decreased dramatically in the presence of competing ions. This effect was observed even when the molar fraction of the two competing cations was kept constant. Anodal flux of mannitol decreased with drug concentration, indicating a possible alteration of the skin permselectivity. In the absence of competing co-ions, ropinirole transport number reached a maximum value (8-13%). In these conditions, the main factor controlling drug delivery was the intensity of current applied. Conclusions. Transdermal iontophoresis allowed the delivery of therapeutic doses of ropinirole. The dose administered and the input rate were controlled by the judicious choice of the key delivery factors here described.

Iontophoretic permselectivity of mammalian skin:characterization of hairless mouse and porcine membrane models

AbstractPurpose. To evaluate the transport number of Na+, and the isoelectric point, of two skin membranes frequently used for iontophoreticin vitroresearch. Methods. Na+ transport numbers were determined by the Hittorf method or by the measurement of membrane potential. The skin isoelectric point was deduced from the electroosmosis of mannitol (a polar non-electrolyte) as a function of pH. Results. The Na+ transport number across porcine skin, like that for hairless mouse, indicated a modest cation permselectivity. Consistent with this observation, the isoelectric points of porcine and hairless mouse skin were determined to be in the ranges of 3.5−3.75 and 4.5−4.6, respectively. That is, at physiological pH, both of these model membranes supports a net negative charge. Conclusions. The permselective properties of porcine and hairless mouse skin are similar (but with the porcine membrane having apparently fewer basic or more weakly-acidic groups than that of the mouse) and consistent with the characteristics, which have been deduced elsewhere, of human skin.

NMR techniques in drug delivery: application to zein protein complexes.

Zein is a protein containing a large amount of nonpolar amino acids, which has shown the ability to form aggregates and entrap solutes, such as drugs and amino acids. NMR techniques were used to detect binding interactions and measure affinity between zein and three different drugs: tetracycline, amoxicillin and indomethacin. The release study of zein microparticle formulations containing any of these drugs was confronted with the affinity results, showing a remarkable correlation. The feasible methodology employed, focused in the functionality of the protein-drug interaction, can be very promising for the rational design of appropriate drug vehicles for drug delivery.

Cyclodextrin based rotaxanes, polyrotaxanes and polypseudorotaxanes and their biomedical applications.

For years, great efforts have been made by scientists to construct various novel interlocked supramolecular systems. A wide range of pseudorotaxanes and rotaxanes, full of challenging constructions and potential applications in areas such as nanostructured functional materials, molecular switches, molecular logic gates, molecular wires, memory devices Willner and biomedical applications have been reported recently. Cyclodextrin polyrotaxantes or polypseudorotaxanes there are not only nice and interesting supramolecular architectures but they also have a high interest for biomaterials application that allow to opened up new approaches for tissue regeneration, drug and gene delivery. The use of the supramolecular cyclodextrins complexes has given rise to interesting studies to design and develop new biomaterials with advanced properties. In this review we will update the recent advances in the use of CDs-supramolecular structures for develop new and advanced drug and gene delivery systems and for use in tissue engineering.

Effect of zein on biodegradable inserts for the delivery of tetracycline within periodontal pockets

Treatment with antibiotics within the periodontal pocket against bacterial infections represents a useful and adjunctive tool to conventional therapy for healing and teeth preservation. With this function in view, an implantable, tetracycline delivery device for the treatment of periodontal disease was developed. The aim of this study was to develop biodegradable, tetracycline-loaded microparticles made of two polymers: PLGA and zein which were compressed into monolithic devices. In this polymer delivery system, the encapsulation efficiency, release characteristics, drug–polymer interaction, and antibacterial activity of loaded drug were investigated. The interaction of tetracycline with the corn protein zein was studied by nuclear magnetic resonance (NMR), Fourier transform infrared, and X-ray diffraction. The hydrophobic interaction of tetracycline with zein in the formulations was deduced from the NMR studies, whereas X-ray diffraction studies showed a new crystalline state of the drug in the presence of the protein. Zein was not denatured by preparation of inserts. Sustained release of tetracycline was obtained, and the proportion of zein in the inserts had a great impact on the drug release. Finally, an effective tetracycline release from inserts against Staphylococcus aureus was achieved over 30 days. In conclusion, the PLGA:zein delivery system described in this study was found to be effective in controlled delivery of tetracycline, and hence may be suitable for intra-pocket delivery of antimicrobial agents in the treatment of periodontitis.

Development of a novel AMX-loaded PLGA/zein microsphere for root canal disinfection

The aim of this study was to develop polymeric biodegradable microspheres (MSs) of poly(D-L lactide-co-glycolide) (PLGA) and zein capable of delivering amoxicillin (AMX) at significant levels for root canal disinfection. PLGA/zein MSs were prepared using a spray-drying technique. The systems were characterized in terms of particle size, morphology, drug loading and in vitro release. Drug levels were reached to be effective during the intracanal dressing in between visits during the endodontic treatment. In vitro release studies were carried out to understand the release profile of the MSs. Antimicrobial activity of AMX was performed by antibiograms. Enterococcus faecalis was the bacteria selected due to its prevalence in endodontic failure. Drug microencapsulation yielded MSs with spherical morphology and an average particle size of between 5 and 38 µm. Different drug-release patterns were obtained among the formulations. Release features related to the MSs were strongly dependent on drug nature as it was demonstrated by using a hydrophobic drug (indomethacin). Finally, AMX-loaded MSs were efficient against E faecalis as demonstrated by the antibiogram results. In conclusion, PLGA/zein MSs prepared by spray drying may be a useful drug delivery system for root canal disinfection.

A vaccine based on biodegradable microspheres induces protective immunity against scuticociliatosis without producing side effects in turbot

The histiophagous scuticociliate parasite Philasterides dicentrarchi is an emergent pathogen in aquaculture and causes significant economic losses on turbot (Scophthalmus maximus) farms. In this study, the surface antigens (Ag) of the parasite were encapsulated and covalently linked to a polymeric microparticle formulation composed of two biodegradable polymers (chitosan and Gantrez). The antigenicity of the formulation and the protection provided were compared in mice and turbot. This formulation induced a higher antibody (Ab) response in mice at doses of 5mg of microspheres (MS) conjugated with approximately 230 μg of Ag (MS-Ag(c)). However, Ab levels were significantly lower than in mice vaccinated with the same concentration of Ag in complete Freunds adjuvant (FCA). In turbot, the MS-Ag(c) formulation induced a higher level of Abs than that induced by the same vaccine emulsified in FCA. The challenge experiments performed with P. dicentrarchi and vaccinated turbot also showed a clear correlation between Ab levels and survival levels. Growth was significantly affected in fish vaccinated with FCA, but not in fish vaccinated with MS. The high adjuvant capacity of MS, together with its biodegradability and low toxicity to fish, makes this new vaccine an economical, effective and safe alternative to oil-based adjuvants for the immunoprophylaxis of scuticociliatosis in turbot.

Cyclodextrins: More than Pharmaceutical Excipients

Cyclodextrins are pharmaceutical excipients used to enhance the solubility, stability, safety and bioavailability of drugs. Recent findings have shown them to display adjuvant activity in vaccine therapy and prophylactic and therapeutic activity in the treatment of several host-pathogen infections. This article focuses on their activity and mechanism of action.

Incorporation of PVMMA to PLGA MS enhances lectin grafting and their in vitro activity in macrophages

Attachment of lectins, especially those that are recognized and bounded by macrophages and other antigen presenting cells onto biodegradable microspheres surface, may serve as support for a wide variety of applications. The aim of this work was: (1) to prepare microspheres (MS) based on two biodegradable copolymers, poly (lactide-co-glicolide) acid (PLGA) and poly[(methyl vinyl ether)-co-(maleic anhydride)] (PVMMA) with their surface functionalized with Concanavalin A (Con A) and, (2) to evaluate their behaviour in macrophage culture. The incorporation of PVMMA was studied in order to augment the lectin coupling efficiency. MS were obtained by spray-drying and bovine serum albumin (BSA) was loaded as protein model. Particles were characterized for size, morphology, surface charge, entrapment efficiency, FTIR, in vitro protein release and conjugation efficiency. Finally, functionalized MS were tested in vitro with raw 264.7 murine macrophages (Mф) in terms of cytotoxicity, phagocytosis, nitric oxide (NO) production, and oxygen consumption. Conjugated Con A microspheres showed increased grafting efficiency up to four times compared to PLGA alone. The retention of Con A after coupling was confirmed by desorption studies. The attachment of Con A to microspheres induced oxygen consumption, increased phagocytosis efficiency and even NO production by macrophages. The results suggest that Con A and possibly, other lectins, grafted onto PLGA-PVMMA microspheres may serve as potential adjuvants by modulating protein delivery and macrophage activation.

Non-MCC materials as extrusion-spheronization aids in pellets production

Microcrystalline cellulose (MCC) is the most widely used base excipient for pellet formulations, mainly because it provides wet masses with appropriate rheological properties for extrusion-spheronization. However, MCC has certain limitations that hinder its universal use in extrusion-spheronization, namely the fact that pellets do not disintegrate after releasing the drug and pellets do not efficiently control the release of highly hydrophilic drugs. This review focuses on materials that can totally or partially replace MCC in order to optimize the properties and the quality of pellets produced by the extrusion-spheronization. The use of other cellulosic materials and natural excipients, such as saccharides, oligosaccharides, starch, alginate, chitosan, pectinic acid or carrageenans, or synthetic polymers, mainly polyacrylates and polyvinylpyrrolidone, is revisited and their effects on the properties of the final pellets are discussed. The approaches applied to produce the pellets and their ability to regulate drug delivery are also illustrated.