Donatella Paolino | Magna Graecia Catanzaro (original) (raw)

Papers by Donatella Paolino

Scientific Reports, 2015

The encapsulation of miR-34a into chitosan/PLGA nanoparticles in order to obtain nanoplexes usefu... more The encapsulation of miR-34a into chitosan/PLGA nanoparticles in order to obtain nanoplexes useful for the modulation of the biopharmaceutical features of the active compound was studied. The nanoplexes were obtained through nanoprecipitation and were characterized by a mean diameter of ~160 nm, a good size distribution and a positive surface charge. The structure of the nanoparticles allowed a high level of entrapment efficiency of the miR-34a and provided protection of the genetic material from the effects of RNase. A high degree of transfection efficiency of the nanoplexes and a significant in vitro antitumor effect against multiple myeloma cells was demonstrated. The therapeutic properties of the nanoplexes were evaluated in vivo against human multiple myeloma xenografts in NOD-SCID mice. The systemic injection of miR-34a mimic-loaded nanoparticles significantly inhibited tumor growth and translated into improved survival of the laboratory mice. RT-PCR analysis carried out on retrieved tumors demonstrated the presence of a high concentration of miR-34a mimics. The integrity of the nanoplexes remained intact and no organ toxicity was observed in treated animals.

Neuroscience Letters, Jan 18, 2010

The purpose of this investigation was to explore the potentiality of a novel animal model to be u... more The purpose of this investigation was to explore the potentiality of a novel animal model to be used for the in vivo evaluation of the ability of a drug delivery system to promote the passage through the blood-brain barrier (BBB) and/or to improve the brain localization of a bioactive compound. A Tween 80-coated poly-L-lactid acid nanoparticles was used as a model of colloidal drug delivery system, able to trespass the BBB. Tacrine, administered in LiCl pre-treated rats, induces electrocorticographic seizures and delayed hippocampal damage. The toxic effects of tacrine-loaded poly-L-lactid acid nanoparticles (5mg/kg), a saline solution of tacrine (5mg/kg) and an empty colloidal nanoparticle suspension were compared following i.p. administration in LiCl-pre-treated Wistar rats. All the animals treated with tacrine-loaded nanoparticles showed an earlier outcome of CNS adverse symptoms, i.e. epileptic onset, with respect to those animals treated with the free compound (10 min vs. 22 min respectively). In addition, tacrine-loaded nanoparticles administration induced damage of neuronal cells in CA1 field of the hippocampus in all treated animals, while the saline solution of tacrine only in 60% of animals. Empty nanoparticles provided similar results to control (saline-treated) group of animals. In conclusion, the evaluation of time-to-onset of symptoms and the severity of neurodegenerative processes induced by the tacrine-lithium model of epilepsy in the rat, could be used to evaluate preliminarily the capability of a drug delivery system to trespass (or not) the BBB in vivo.

Journal of Chromatography A, 2015

This paper reports a new, easy, cheap, and fast MEPS-HPLC-PDA method for the simultaneous analysi... more This paper reports a new, easy, cheap, and fast MEPS-HPLC-PDA method for the simultaneous analysis of ciprofloxacin and levofloxacin, two fluoroquinolones (FLQs) commonly used for the treatment of pulmonary infections in cystic fibrosis (CF) patients. The FLQs were resolved on a Discovery C8 column (250mm×4.6mm; 5μm particle size) using an isocratic elution with a run time of 15min, without further purification. The method was validated over concentrations ranging from 0.05 to 2μg/mL for both analytes in human sputum, and enrofloxacin was used as internal standard. This method was successfully tested to detect FLQs in sputum collected from CF patients. The MEPS-HPLC-PDA method was validated using biological samples collected from CF patients orally or intravenously injected with FLQs. The resultant data showed that the method is selective, sensitive and robust over range of concentrations for both FLQs. The limit of quantification of the method was 0.05μg/mL for both analytes (comparable to more complex and expensive instrument configurations), weighted-matrix-matched standard curves showed a good linearity up to 2μg/mL, and parallelism tests were also successfully assessed. The intra- and inter-day precision (RSD%) values were ≤10.4% and ≤11.1%, respectively, for all range of analysis. The intra- and inter-day trueness (Bias%) values are ranged from -11.8% to 7.25% for both antibiotic drugs. At the best of our knowledge, this is the first MEPS-HPLC-PDA based method that uses MEPS procedure for simultaneous determination of ciprofloxacin and levofloxacin in human sputum. The method was tested successfully on real sputum samples by following a conventional drug administration. Furthermore, the MEPS-HPLC-PDA based method provides more advantages to detect and analyze quickly the antibiotic drugs in biological matrices than other analytical procedures reported in literature.

A perspective drug delivery systems can be defined as mechanisms to introduce therapeutic agents ... more A perspective drug delivery systems can be defined as mechanisms to introduce therapeutic agents into the body. Chewing leaves and roots of medical plants and inhalation of soot from the burning of medical substances are examples of drug delivery from the earliest times. However, these primitive approaches of delivering drugs lacked a very basic need in drug delivery; that is, consistency and uniformity (a required drug dose). This led to the development of different drug delivery methods in the later part of the eighteenth and early nineteenth century. Those methods included pills,

Colloids and Surfaces B: Biointerfaces, 2015

The analytical tools allow the detection of bioactive compounds, diagnostic agents and chemothera... more The analytical tools allow the detection of bioactive compounds, diagnostic agents and chemotherapeutics. Recently, new methods have been developed to analyze pharmaceutical samples and ingredients. In this attempt, analytical parameters, e.g., the lack of trueness, robustness and sensitivity, play a pivotal role to quantify and analyze molecules, both for diagnostic applications as well as therapeutic treatments. Spectrophotometers and spectrofluorometers are apparatus for easy and rapid quantification of molecular probes and chemotherapeutics into cells, plasma and tissues. However, they lack accuracy and precision. Conversely, HPLC provides the maximum resolution to detect and separate fluorescent probes and chemotherapeutics after their incubation in cells, plasma and tissues. The aim of this work was to develop an HPLC method that easily detects molecular and fluorescent probes, e.g., Nile Red, in biological samples. To improve the robustness of the method, Nile Red was analyzed before and after loading into niosomes made from Tween 20 and 21, respectively. A significant difference was further obtained by comparing the entrapment efficacy percentage of niosomes made from Tween 21 (42.23%) and Tween 20 (53.25%). The comparison between HPLC and spectrofluorometer assays showed differences between the two methods in terms of limit of detection, linearity and accuracy. The resulting data demonstrated that the HPLC-FLD provides a limit of detection for Nile Red of 0.1ng/mL, and a good linearity up to 62.5ng/mL. The HPLC-FLD analysis showed a limit of quantification value for a total mass of Nile Red 1200-folds better than data previously reported in studies; and 312-folds better than the spectrofluorometer analysis. Additionally, results show that the HPLC-FLD increases the sensitivity for biological samples compared to the spectrofluorometer. The Nile Red-loaded niosomes were also incubated at different times with HEK-293 cells. In vitro results demonstrated that the HPLC-FLD apparatus detects Nile Red-loaded niosomes at higher concentrations into HEK-293 cells than the spectrofluorometer. The intracellular uptake of Nile Red was increased at 120 and 24min using niosomes made from Tween 20 and 21, respectively, and its intracellular accumulation shows a time-dependent internalization over 120min of incubation time.

Journal of Drug Targeting

Biphenylylacetic acid (BPAA) was linked to the free hydroxyl group of 2,6-di-O-methyl-beta-Cyclod... more Biphenylylacetic acid (BPAA) was linked to the free hydroxyl group of 2,6-di-O-methyl-beta-Cyclodextrin (DM-beta-CyD) through an ester linkage to obtain the site specific release of the drug to the colon. The conjugate at 1:1 mole ratio was separated from the reaction mixture by semipreparative reverse-phase HPLC and characterized by 1H-NMR, 13C-NMR, IR spectroscopy, mass spectrometry and elemental analysis. Chemico-physical characteristics, such as water solubility and dissolution rate, were evaluated comparatively to the BPAA-DM-beta-CyD inclusion complex. Hydrolysis rates were investigated in media simulating gastro-intestinal fluids and at pH 7.4 in the presence of porcine liver esterase. A rapid release of the drug was observed at acid pH value. In all cases a first order kinetic was observed, characterized by t1/2 value of 1.19, 19 and 4 h for chemical hydrolysis at pH 1.1, at pH 7.4 and enzymatic hydrolysis, respectively. In vitro permeation studies through caco-2 cells confi...

Confocal laser scanning microscopy (CLSM) is a suitable tool used for investigating the physico-c... more Confocal laser scanning microscopy (CLSM) is a suitable tool used for investigating the physico-chemical features of pharmaceutics and analyzing their performance in numerous in vitro and in vivo models. Even though the applications of this technology are manifold, during the last decade it has been particularly applied in the field of drug delivery. In fact, CLSM allows the recognition of the interaction phenomena that occur between micro-/nano-systems and cells, the investigation of the localization of many colloids inside cells, and the exploration of the permeation/diffusion rates of these systems through biological barriers (i.e. blood brain barrier, gastrointestinal epithelium, pulmonary tissue, skin layers). In detail, CLSM is helpful in distinguishing the cell interaction/permeation profiles of fluorescent micro-and nano-pharmaceutics as a function of their technological properties and in furnishing the evidence of efficient selective targeting through the use of suitable co...

Advances in Colloid and Interface Science

Efficient and safe drug delivery has always been a challenge in medicine. The use of nanotechnolo... more Efficient and safe drug delivery has always been a challenge in medicine. The use of nanotechnology, such as the development of nanocarriers for drug delivery, has received great attention owing to the potential that nanocarriers can theoretically act as "magic bullets" and selectively target affected organs and cells while sparing normal tissues. During the last decades the formulation of surfactant vesicles, as a tool to improve drug delivery, brought an ever increasing interest among the scientists working in the area of drug delivery systems. Niosomes are self assembled vesicular nanocarriers obtained by hydration of synthetic surfactants and appropriate amounts of cholesterol or other amphiphilic molecules. Just like liposomes, niosomes can be unilamellar or multilamellar, are suitable as carriers of both hydrophilic and lipophilic drugs and are able to deliver drugs to the target site. Furthermore, niosomal vesicles, that are usually non-toxic, require less productio...

International Journal of Pharmaceutics, 2015

Ultradeformable liposomes represent useful formulations able to increase the skin permeation of d... more Ultradeformable liposomes represent useful formulations able to increase the skin permeation of drug compounds. In this study, resveratrol- and 5-fluorouracil-loaded ultradeformable liposomes were investigated for the potential treatment of non-melanoma skin cancer. The in vitro anticancer activity of ultradeformable liposomes was tested on human skin cancer cells through viability-, cell cycle- and apoptosis-analysis. Furthermore, we tested the percutaneous permeation of ultradeformable liposomes using human stratum corneum and viable epidermis. The co-encapsulation of resveratrol and 5-fluorouracil (multi-drug carrier) in ultradeformable liposomes improved their anticancer activity on skin cancer cells as compared to both the free drug form and the single entrapped agents. These multi-drug ultradeformable liposomes arrest cell proliferation in G1/S, thus modifying the action of 5-fluorouracil and increasing the activity of resveratrol. This effect might depend on the ultradeformable liposomes, which may accumulate in deeper skin layers, thus generating a cutaneous depot from which resveratrol and 5-fluorouracil are gradually released. Resveratrol and 5-fluorouracil co-loaded ultradeformable liposomes could be a new nanomedicine for the treatment of squamous cell carcinoma, i.e., actinic keratosis, Bowen&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease, and keratoacanthoma.

International journal of cosmetic science, 2008

The effects of different emulsifiers on the in vitro permeation through human skin of two sunscre... more The effects of different emulsifiers on the in vitro permeation through human skin of two sunscreen agents [octylmethoxycinnamate (OMC) and butylmethoxydibenzoylmethane (BMBM)] were investigated from O/W emulsions. The test formulations were prepared using the same oil and aqueous phase ingredients and the following emulsifier and coemulsifier systems: Emulgade SE((R)) (ceteareth-12 and ceteareth-20 and cetearyl alcohol and cetyl palmitate) and glycerylmonostearate (emulsion 1); Brij 72((R)) (steareth-2), Brij 721((R)) (steareth-21) and cetearyl alcohol (emulsion 2); Phytocream((R)) (potassium palmitoyl-hydrolysed wheat protein and glyceryl stearate and cetearyl alcohol) and glycerylmonostearate (emulsion 3); Montanov 68((R)) (cetearyl glucoside and cetearyl alcohol) (emulsion 4); Xalifin-15((R)) (C(15-20) acid PEG-8 ester) and cetearyl alcohol (emulsion 5). The cumulative amount of OMC that permeated in vitro through human skin after 22 h from the formulations being tested decrease...

International journal of pharmaceutics, Jan 11, 2006

We evaluated the ability of two modified cyclodextrins, hydroxypropyl-beta-cyclodextrin (HP-beta-... more We evaluated the ability of two modified cyclodextrins, hydroxypropyl-beta-cyclodextrin (HP-beta-Cyd) and 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-Cyd), to influence the percutaneous absorption through isolated human stratum corneum and epidermis (SCE) of celecoxib (CCB). Previous studies demonstrated that DM-beta-Cyd includes the drug, producing a significant increase of water solubility (0.5 mg/ml at 25 degrees C) and dissolution rate of CCB. In this work chemical-physical characterization studies were performed to evaluate the ability of HP-beta-Cyd to include CCB. We showed that only an external interaction could exist between CCB and HP-beta-Cyd that positively influences the water solubility of the drug (0.12 mg/ml at 25 degrees C for CCB-HP-beta-CyD system and 4.12 x 10(-3) mg/ml at 25 degrees C for free CCB). In vitro percutaneous experiments were performed using samples in solution and in suspension containing different Cyd concentrations. Both HP-beta-Cyd and DM-beta-Cyd...

Pharmaceutical research, 2003

The evaluation of nanosphere colloidal suspensions containing acyclovir as potential ophthalmic d... more The evaluation of nanosphere colloidal suspensions containing acyclovir as potential ophthalmic drug delivery systems was carried out. The influence of polymer molecular weight and type and concentration of various surfactants on nanosphere properties was studied. The ocular pharmacokinetics of acyclovir-loaded nanoparticles was evaluated in vivo and compared with an aqueous suspension of the free drug. Nanospheres were made up of poly-d,l-lactic acid (PLA). The colloidal suspension was obtained by a nanoprecipitation process. The surface properties of PLA nanospheres were changed by the incorporation of pegylated 1,2-distearoyl-3-phosphatidylethanolamine. The mean size and zeta potential of the nanospheres were determined by light scattering analysis. The acyclovir loading capacity and release were also determined. In vivo experiments were carried out on male New Zealand rabbits. The ocular tolerability of PLA nanospheres was evaluated by a modified Draize test. The aqueous humor a...

Pharmaceutical research, 2002

The protective antioxidant role of idebenone both as free drug and drug-loaded Tween 80-coated po... more The protective antioxidant role of idebenone both as free drug and drug-loaded Tween 80-coated polyethyl-2-cyanoacrylate (PECA) nanocapsules is reported. The relationship between oxidative damage and apoptotic or nonapoptotic cell death is evaluated in vitro. Idebenone-loaded nanocapsules were prepared with the interfacial polymerization method in the presence of Tween 80. Human nonimmortalized fibroblasts. under different stress conditions, either 0.5 mM diethylmaleate (DEM) for 60 min or 0.1 mM H2O2 for 30 min, were used as the experimental in vitro model. The production of reactive oxygen species, the cell viability, and the nuclear DNA damage were evaluated. The presence of apoptotic damage was evaluated both by the determination of caspase-3-like protein activity and by Promega's fluorescent apoptotic detection system. DEM and H2O2 affected the cultured cells in different ways. DEM induced a moderate cellular insult, which was efficaciously antagonized by idebenone-loaded P...

Journal of cosmetic science

The effects of different silicone emulsifiers on the in vitro permeation through human skin of tw... more The effects of different silicone emulsifiers on the in vitro permeation through human skin of two sunscreens (octylmethoxycinnamate, OMC, and butylmethoxydibenzoylmethane, BMBM) were investigated from cosmetic emulsions. The formulations being tested were prepared using the same oil and aqueous phase ingredients and the following silicone emulsifiers: dimethicone copolyol and cyclomethicone (emulsion 1), cetyldimethicone copolyol (emulsion 2), polyglyceryl-4-isostearate and cetyldimethicone copolyol and hexyllaurate (emulsion 3), lauryldimethicone copolyol (emulsion 4), and cyclomethicone and dimethicone copolyol (emulsion 5). The cumulative amount of OMC that permeated in vitro through human skin after 22 h from emulsions 1-5 decreased in the order 2 approximate, equals 1 > 5 > 4 approximate, equals 3 and was about twofold higher from emulsion 2 compared to emulsion 4. As for BMBM, no significant difference was observed in regard to its skin permeation from the emulsions bei...

Journal of Drug Delivery Science and Technology, 2006

Current drug targets, Jan 4, 2014

Nanomedicine involves the use of nanoparticles for therapeutic and diagnostic purposes. During th... more Nanomedicine involves the use of nanoparticles for therapeutic and diagnostic purposes. During the past two decades, a growing number of nanomedicines have received regulatory approval and many more show promise for future clinical translation. In this context, it is important to evaluate the safety of nanoparticles in order to achieve biocompatibility and desired activity. However, it is unwarranted to make generalized statements regarding the safety of nanoparticles, since the field of nanomedicine comprises a multitude of different manufactured nanoparticles made from various materials. Indeed, several nanotherapeutics that are currently approved, such as Doxil and Abraxane, exhibit fewer side effects than their small molecule counterparts, while other nanoparticles (e.g. metallic and carbon-based particles) tend to display toxicity. However, the hazardous nature of certain nanomedicines could be exploited for the ablation of diseased tissue, if selective targeting can be achieve...

BMC neuroscience, Jan 16, 2002

Oxidative stress has shown to contribute in the mechanisms underlying apoptotic cell death occurr... more Oxidative stress has shown to contribute in the mechanisms underlying apoptotic cell death occurring in AIDS-dementia complex. Here we investigated the role of peroxynitrite in apoptosis occurring in astroglial cells incubated with supernatants of HIV-infected human primary macrophages (M/M). Flow cytometric analysis (FACS) of human cultured astrocytes shortly incubated with HIV-1-infected M/M supernatants showed apoptotic cell death, an effect accompanied by pronounced staining for nitrotyrosine (footprint of peroxynitrite) and by abnormal formation of malondialdehyde (MDA). Pretreatment of astrocytes with the peroxynitrite decomposition catalyst FeTMPS antagonized HIV-related astrocytic apoptosis, MDA formation and nitrotyrosine staining. Taken together, our results suggest that inhibition of peroxynitrite leads to protection against peroxidative stress accompanying HIV-related apoptosis of astrocytes. Overall results support the role of peroxynitrite in HIV-related programmed dea...