Z. Panagi
University of Patras
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Featured researches published by Z. Panagi.
Journal of Controlled Release | 2002
Konstantinos Avgoustakis; A. Beletsi; Z. Panagi; P Klepetsanis; Andreas Germanos Karydas; Dionyssis S. Ithakissios
The in vitro nanoparticle degradation, in vitro drug release and in vivo drug residence in blood properties of PLGA-mPEG nanoparticles of cisplatin were investigated. The nanoparticles were prepared by a double emulsion method and characterized with regard to their morphology, size, zeta potential and drug loading. The rate of in vitro degradation of the PLGA-mPEG nanoparticles in PBS (pH 7.4) depended on their composition, increasing when the mPEG content (mPEG:PLGA ratio) of the nanoparticles increased. Sustained cisplatin release over several hours from the PLGA-mPEG nanoparticles in vitro (PBS) was observed. The composition of the nanoparticles affected drug release: the rate of release increased when the mPEG content of the nanoparticles increased. Within the range of drug loadings investigated, the drug loading of the nanoparticles did not have any significant effect on drug release. The loading efficiency was low and needs improvement in order to obtain PLGA-mPEG nanoparticles with a satisfactory cisplatin content for therapeutic application. The i.v. administration of PLGA-mPEG nanoparticles of cisplatin in BALB/c mice resulted in prolonged cisplatin residence in systemic blood circulation. The results appear to justify further investigation of the suitability of the PLGA-mPEG nanoparticles for the controlled i.v. delivery and/or targeting of cisplatin.
International Journal of Pharmaceutics | 2001
Z. Panagi; A. Beletsi; Gregory P. Evangelatos; Evangelia Livaniou; Dionyssis S. Ithakissios; Konstantinos Avgoustakis
The effect of nanoparticle dose on the biodistribution and pharmacokinetics of conventional PLGA and stealth poly(Lactide-co-glycolide)-monomethoxypoly(ethyleneglycol) (PLGA-mPEG) nanoparticles was investigated. The precipitation-solvent diffusion method was used to prepare PLGA and PLGA-mPEG nanoparticles labeled with 125I-cholesterylaniline. These were administered intravenously (i.v.) in mice and at predetermined time intervals the animals were sacrificed and their tissues were excised and assayed for radioactivity. Within the dose range applied in this study, blood clearance and mononuclear phagocyte system (MPS) uptake of the PLGA nanoparticles depended on dose whereas they were independent of dose in the case of the PLGA-mPEG nanoparticles. Increasing the dose, decreased the rates of blood clearance and MPS uptake of the PLGA nanoparticles, indicating a certain degree of MPS saturation at higher doses of PLGA nanoparticles. The dose affected the distribution of PLGA nanoparticles between blood and MPS (liver) but it did not affect the nanoparticle levels in the other tissues. Within the range of doses applied here, the PLGA nanoparticles followed non-linear and dose-dependent pharmacokinetics whereas the PLGA-mPEG nanoparticles followed linear and dose-independent pharmacokinetics. In addition to the prolonged blood residence, the dosage-independence of the pharmacokinetics of the PLGA-mPEG nanoparticles would provide further advantages for their application in controlled drug delivery and in drug targeting.
International Journal of Pharmaceutics | 2003
Konstantinos Avgoustakis; A. Beletsi; Z. Panagi; Pavlos Klepetsanis; Evangelia Livaniou; Gregory P. Evangelatos; Dionyssis S. Ithakissios
The physicochemical properties, the colloidal stability in vitro and the biodistribution properties in mice of different PLGA-mPEG nanoparticle compositions were investigated. The nanoparticles were prepared by a precipitation-solvent evaporation technique. The physical characteristics and the colloidal stability of the PLGA-mPEG nanoparticles were significantly influenced by the composition of the PLGA-mPEG copolymer used to prepare the nanoparticles. PLGA-mPEG nanoparticles prepared from copolymers having relatively high mPEG/PLGA ratios were smaller and less stable than those prepared from copolymers having relatively low mPEG/PLGA ratios. All PLGA-mPEG nanoparticle compositions exhibited prolonged residence in blood, compared to the conventional PLGA nanoparticles. The composition of the PLGA-mPEG copolymer affected significantly the blood residence time and the biodistribution of the PLGA-mPEG nanoparticles in liver, spleen and bones. The in vivo behavior of the different PLGA-mPEG nanoparticle compositions did not appear to correlate with their in vitro stability. Optimum mPEG/PLGA ratios appeared to exist leading to long blood circulation times of the PLGA-mPEG nanoparticles. This may be associated with the effects of the mPEG/PLGA ratio on the density of PEG on the surface of the nanoparticles and on the size of the nanoparticles.
International Journal of Pharmaceutics | 2010
George Mattheolabakis; George Lagoumintzis; Z. Panagi; Evangelia Papadimitriou; Charalambos D. Partidos; Konstantinos Avgoustakis
We investigated the influence of antigen entrapment in PLA nanoparticles on the immune responses obtained after transcutaneous immunization. OVA-loaded PLA nanoparticles were prepared using a double emulsion process. Following application onto bare skin of mice in vivo, fluorescence-labeled nanoparticles were detected in the duct of the hair follicles indicating that the nanoparticles can penetrate the skin barrier through the hair follicles. Although the OVA-loaded nanoparticles elicited lower antibody responses than those induced by OVA in aqueous solution they were more efficient in inducing cytokine responses. In vitro re-stimulation of cultured splenocytes with OVA elicited a little higher levels of IFN-gamma (difference statistically insignificant, p>0.05) and significantly higher levels of IL-2 (p<0.001) in mice immunized with OVA-loaded nanoparticles compared to those immunized with OVA in solution. In the presence of CT, the OVA-loaded nanoparticles induced significantly higher IFN-gamma and IL-2 than all other formulations. Transcutaneous administration of OVA encapsulated in the PLA nanoparticles exhibited priming efficacy to a challenging dose of OVA given via different route. These findings indicate the potential of nanoparticles to deliver antigens via the transcutaneous route and prime for antibody and strong cellular responses. The co-administration of an adjuvant such as CT had the added advantage of modulating the immune response, a desirable characteristic within the context of vaccination against intracellular versus extracellular pathogens.
Current Eye Research | 2010
G. Blatsios; A. S. Tzimas; George Mattheolabakis; Z. Panagi; Konstantinos Avgoustakis; Sotirios P. Gartaganis
Purpose: To develop scleral controlled-release-systems of triamcinolone acetonide (TA) based on biodegradable poly(lactide) (PLA). Materials and Methods: (1) PLA microspheres containing TA were prepared by a single or double emulsification-solvent evaporation method. Morphology, size, effect of drug input and method of microsphere preparation on drug loading, and in vitro TA release of the microspheres were investigated. (2) Mini-tablets consisting of blank PLA-microspheres and TA (weight ratios of 1:1, 2:1, and 4:1, respectively) were developed and their release profile in vitro was evaluated. (3) The in vitro transscleral diffusion profile was evaluated by placing a PLA-TA (1:1) tablet in a donor chamber and measuring the TA concentration in a receptor chamber. Donor and receptor chambers were separated by rabbit sclera. (4) Two cadaver rabbit eyes received a 1:1 PLA-TA tablet episclerally, which was covered by a scleral patch. TA aqueous humor and vitreous concentrations were measured 5, 10, and 20 days post implantation. Results: (1) Microsphere average size was 2 μm. The double emulsification method and increasing drug input led to an increase in drug loading and encapsulation. Sustained release of TA over several days from the microspheres in vitro was observed, with the rate of release being affected by their TA content. (2) TA exhibited sustained release profile from the PLA-TA tablets, with the rate of release being affected by the PLA:TA ratio. (3) TA could slowly cross the sclera tissue in vitro, with approximately 21% of the drug loaded in the donor compartment being diffused through the sclera in 45 days. (4) Following scleral administration of the PLA-TA mini-tablets, TA accumulated in the vitreous and aqueous humor of cadaver eyes. Conclusions: The PLA-TA microspheres and mini-tablets appear promising for the controlled transscleral delivery of TA and justify further investigation.
International Journal of Pharmaceutics | 1999
Z. Panagi; Konstantinos Avgoustakis; Gregory P. Evangelatos; Dionyssis S. Ithakissios
The in vitro binding of the serum proteins human serum albumin (HSA), human serum immunoglobulin (IgG) or human serum high density lipoprotein (HDL) on unilamellar liposomes of different lipid composition was studied. HDL bound on liposomes at higher amounts than IgG and IgG at higher amounts than HSA. The protein binding on liposomes decreased when bovine brain monosialganglioside (GM1) or poly(ethyleneglycol)-distearoylphosphatidylethanolamine (DSPE-PEG) was included in liposome membrane. With all three proteins, an inverse relationship was found between the amount of protein bound on liposomes after 1 h liposome–protein incubation in vitro and the BLOOD/RES ratio of the same liposomes 2 min after i.v. administration in mice (Panagi et al., Drug Dev. Ind. Pharm., 22 (1996) 217–224). The potential value of this in vitro–in vivo correlation, provided it is extended to additional liposome compositions, is that it may provide an in vitro method to screen liposomes in terms of blood clearance rates.
Drug Development and Industrial Pharmacy | 1996
Z. Panagi; Christine Sawas-dimopoulou; Konstantinos Avgoustakis; Dionyssis S. Ithakissios
AbstractLabeling of preformed liposomes with 99mTc is a simple, quick, and highly versatile method, and its potential in the comparative screening of preformed liposomes with regard to their early biodistribution properties, such as the BLOOD/RES ratios at 2 and 30 min postadministration, was investigated. Liposomes differing in lipid composition and size were prepared and labeled under optimum conditions with 99mTc using a slight modijication of a previously described method (1). The amount of SnCl2 used to reduce pertechnetate affected liposome biodistribution. The labeling method employed was capable of detecting anticipated changes in liposome biodistribution caused by alterations in liposome composition or size. It could also reveal the effect of a relative immiscibility of monosialganglioside GM1 with di-myristoy1-phosphatidyl-choline:di-myristoyl-phosphatidyl-glycerol (DMPC:DMPG) on the biodistribution of DMPC:DMPG:GM, liposomes. It is proposed that 99mTc labeling of liposomes provides a tool for f...
International Journal of Pharmaceutics | 2005
A. Beletsi; Z. Panagi; Konstantinos Avgoustakis
Journal of Biomedical Materials Research Part A | 2005
N. Stivaktakis; K. Nikou; Z. Panagi; A. Beletsi; Leondios Leondiadis; Konstantinos Avgoustakis
Journal of Biomedical Materials Research Part A | 2004
N. Stivaktakis; K. Nikou; Z. Panagi; A. Beletsi; Leondios Leondiadis; Konstantinos Avgoustakis