A scalable platform to prepare multi-functional ocular lenses is demonstrated. Using rapidly diss... more A scalable platform to prepare multi-functional ocular lenses is demonstrated. Using rapidly dissolving polyvinylpyrrolidone (PVP) as the active stabilizing matrix, both sides of ocular lenses were coated using a modified scaled-up masking electrohydrodynamic atomization (EHDA) technique (flow rates variable between 5 and 10 µL/min, applied voltage 4-11 kV). Each side was coated (using a specially designed flip-able well) selectively with a pre-determined morphology and model drug substance. PVP nanoparticles (inner side, to be in contact with the cornea, mean size <ca.100 nm) were encapsulated with a probe (flourescein dye) and PVP nanofibres (outer side, to be exposed to air and eye lid, mean width size <ca.200 nm) were encapsulated with chloramphenicol (5 w/w% PVP). Release of the probe and anti-microbial activity (using Staphylococcus aureus NCTC 6571) were demonstrated based on rapid dissolution and contact of PVP model substance matrix. Adapting these findings further fo...
To synthesize pegylated stoichiometrically and structurally well-defined conjugates of fullerene ... more To synthesize pegylated stoichiometrically and structurally well-defined conjugates of fullerene (C60) with doxorubicin (DOX) and investigate their antiproliferative effect against cancer cell lines. Stoichiometric (1:1 and 1:2) pegylated conjugates of C60 with DOX were synthesized using the Prato reaction to create fulleropyrrolidines equipped with a carboxyl function for anchoring a polyethylene glycol (PEG) moiety and either a hydroxyl group for attaching one molecule of DOX or a terminal alkyne group for attaching two molecules of DOX through a click reaction. In both conjugates, the DOX moieties are held through a urethane-type bond. Drug release was studied in phosphate buffer (PBS, pH 7.4) and MCF-7 cancer cells lysate. The uptake of the conjugates by MCF-7 cancer cells and their intracellular localization were studied with fluorescence microscopy. The antiproliferative activity of the conjugates was investigated using the WST-1 test. One or two DOX molecules were anchored on pegylated C60 particles to form DOX-C60-PEG conjugates. Drug liberation from the conjugates was significantly accelerated in the presence of tumor cell lysate compared to PBS. The conjugates could be internalized by MCF-7 cells. DOX from the conjugates exhibited much delayed, compared to free DOX, localization in the nucleus and antiproliferative activity. Pegylated DOX-C60 conjugates (1:1) and (2:1) with well-defined structure were successfully synthesized and found to exhibit comparable, but with a delayed onset, antiproliferative activity with free DOX against MCF-7 cancer cells. The results obtained justify further investigation of the potential of these conjugates as anticancer nanomedicines.
ABSTRACT We investigated the behavior of the pH and thermo-responsive poly(2-(diethylamino)ethyl ... more ABSTRACT We investigated the behavior of the pH and thermo-responsive poly(2-(diethylamino)ethyl methacrylate-co-methacrylic acid)-b-(ethylene glycolmethylether methacrylate)-b-poly(2-(diethylamino)ethyl methacrylate-co-methacrylic acid) (P(DEAEMA-co-MAA)-b-PEGMA-b-P(DEAEMA-co-MAA)) triblock terpolymers in aqueous solution by means of static and dynamic light scattering, transmission electron microscopy and rheology. Association phenomena were observed at the isoelectric point region of the polyampholyte outer blocks leading to flower-like micelles and at higher polymer concentrations, to a three dimensional transient micellar network, exhibiting a compex thermo-response thanks to the thermo-sensitivity of the PEGMA middle block. Doxorubicin (DOX) drug was loaded in the terpolymer micelles and drug release studies were performed. Controlled drug delivery could be achieved by tuning pH. The terpolymer micelles exhibited satisfactory cytocompatibility towards human umbilical vein endothelial cells.
Purpose of the study was to develop and assess a novel controlled drug delivery system of latanop... more Purpose of the study was to develop and assess a novel controlled drug delivery system of latanoprost acid (LA). Poly(lactide)/Monomethoxy-poly(ethyleneglycol) (PLA-PEG) nanoparticles (NPs) were prepared using an emulsification-solvent evaporation technique. NPs were characterized in vitro according to their size, z-potential, drug entrapment efficiency and LA release. LA-loaded NPs (equivalent to 8.5 mg LA) were administered into the subconjunctival space of normotensive rabbits (group A). A free LA solution of the same drug content was subconjunctivally injected in a second rabbit group (group B), while blank NPs were administered in a third group (group C). A group of untreated animals (group D) served as the control. Intraocular pressure (IOP) was monitored for 8 consecutive days, using the Tono-pen XL. Aqueous humor (AH) levels of LA were evaluated for 6 days post-administration, by means of HPLC. Mean nanoparticle size was 80 nm. The drug entrapment efficiency was 18.3%. NPs sustained the release of LA over several days in vitro. Non-significant differences in baseline IOP were found between groups (p ¼ 0.22). LA-loaded NPs exerted a significant hypotensive effect on group A, while IOP values remained significantly lower compared to the rest groups, throughout the study (p ¼ 0.04). LA AH concentrations in group B continuously decreased with time, while LA levels in group A steadily increased. On day 6, LA levels were higher in group A compared to group B (344 AE 73.5 ng/ml and 228 AE 41.01 ng/ml, respectively). No adverse effects were observed. In conclusion, after subconjunctival administration, the LAloaded NPs provided sustained LA delivery in vivo. They appear to be a promising system for the controlled subconjunctival delivery of LA.
the effectiveness of the drug (Allcock,1990). The properties of macromelecular drugs have been ex... more the effectiveness of the drug (Allcock,1990). The properties of macromelecular drugs have been exploited to reduce the side effects of the antitumour agent (NH3) 2 PtC12. Kidney damage, caused by the readily excreted drug, can be reduced by its reaction with poly(bis-methylaminophosphazene), in which a non-excretable coordination complex is formed (Allen et al., 1977).
The objective of this investigation was to explore the effects of drug solubility on the evolutio... more The objective of this investigation was to explore the effects of drug solubility on the evolution of matrix dimensions and gel layer's during drug release and investigate the relationship between these effects and the mechanism and the rate of drug release. Two hydrophilic swellable polymers Polyox (POL) and cross-linked Carbopol (CARB) were employed as carriers. Caffeine (CAF) and theophylline (THE), two drugs having similar chemical structure but different aqueous solubility, were used as model drugs. Both drug and polymer characteristics were found to influence the dimensional changes of matrices and the development of the gel layer formed around the glassy core. The dimensional expansion in CAF matrices was always more pronounced than the THE matrices. Also the CARB matrices demonstrated greater maximum expansion and lower drug release than the POL matrices, due to a smaller degree of erosion of CARB. The dimensions of CARB/CAF matrices, unlike all the other matrices studied, exhibited a biphasic increase at early times, which was attributed to the cross-linked structure of CARB and the high solubility of CAF. With both polymers, a thinner gel layer was developed in the matrices containing the less soluble THE compared to the CAF matrices. The thickness of the gel layer increased continuously with time in the CAF matrices whereas it increased initially and after reaching a maximum started to decrease in THE matrices. All formulations except those of CARB/THE exhibited burst release, which depended on drug and polymer characteristics. The gel layer thickness and erosion rate appeared to determine the rate of drug release from the CARB and POL formulations. The results clearly indicate that for these matrices gel thickness and fluctuation of gel thickness affect the release rate/h of drug proportionally. Analysis of the release kinetics indicated that CAF was released mainly through diffusion whereas, THE was released mainly through matrix erosion.
Abstract Spray dried poly(lactide-co-glycolide) powders were used to prepare phenobarbitone matri... more Abstract Spray dried poly(lactide-co-glycolide) powders were used to prepare phenobarbitone matrix tablets. The release of phenobarbitone was significantly sustained, indicating the suitability of using poly(lactide-co-glycolide) matrix tablets for long-term controlled drug delivery. Drug release profiles consisted of three regions: there were an initial region of relatively high release rate (burst effect), followed by an extended region of lower and essentially constant release rate from approx. 20 to 80% of drug release. This steady state release region was followed by a final one in which the rate of drug release fell off as exhaustion of the drug in the matrix approached. A composite mechanism of drug release is proposed involving diffusion of the drug through water-filled pores in the matrix and drug diffusion through the swollen polymer. The rate of drug release increased with an increase in the glycolide content of the polymers. Decreasing the polymer molecular weight caused initially an increase but later a decrease in the release rate. These results are discussed in terms of degradation, water uptake and swelling of the polymers upon immersion in aqueous media.
Abstract A spray drying technique was adopted to prepare poly(lactide-co-glycolide) powders. Sign... more Abstract A spray drying technique was adopted to prepare poly(lactide-co-glycolide) powders. Significant difficulties were encountered with the relatively high molecular weight polymers, the spray drying of which produced threads rather than particles, unless very dilute solutions were used (less than 2% w/v). The important factor for the successful ‘spray powdering’ of poly(lactide-co-glycolide) polymers appeared to be the molecular weight of the polymer and not the viscosity of the sprayed solution. The spray dried particles were porous, almost spherical agglomerates of tiny spheres. The agglomerated and rather loose texture of the particles probably enhanced the powder compressibility. Soft and ductile powders were obtained with yield pressure values ranging from 28 to 33 MPa. No correlation was found between polymer properties and yield pressure. The contact angle values between polymer compacts and water were in the range of 72–78°, indicating a moderate polymer hydrophobicity. The molecular weight of the polymers did not have any effect on the contact angle value, whereas an increase in glycolide content tended to lower the contact angle. Water uptake by poly(lactide-co-glycolide) matrices increased steadily as matrix hydrophobicity increased with time due to polymer degradation. The weight of the matrix increased with time but, when mass loss due to degradation outweighed the gain from water absorption, the weight of the matrix began to fall. An increase in glycolide content or a decrease in polymer molecular weight caused an increase in both the percent water uptake rate. The polymers swelled considerably, although they absorbed relatively small amounts of water and this may have significant implications for drug release from poly(lactide-co-glycolide) matrix tablets.
The physicochemical properties, the colloidal stability in vitro and the biodistribution properti... more 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.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Jan 24, 2015
To investigate the application of water-dispersible poly(lactide)-poly(ethylene glycol) (PLA-PEG)... more To investigate the application of water-dispersible poly(lactide)-poly(ethylene glycol) (PLA-PEG) copolymers for the stabilization of graphene oxide (GO) aqueous dispersions and the feasibility of using the PLA-PEG stabilized GO as a delivery system for the potent anticancer agent paclitaxel. A modified Staudenmaier method was applied to synthesize graphene oxide (GO). Diblock PLA-PEG copolymers were synthesized by ring-opening polymerization of dl-lactide in the presence of monomethoxy-poly(ethylene glycol) (mPEG). Probe sonication in the presence of PLA-PEG copolymers was applied in order to reduce the hydrodynamic diameter of GO to the nano-size range according to dynamic light scattering (DLS) and obtain nano-graphene oxide (NGO) composites with PLA-PEG. The composites were characterized by atomic force microscopy (AFM), thermogravimetric analysis (TGA), and DLS. The colloidal stability of the composites was evaluated by recording the size of the composite particles with time an...
Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly ... more Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly M Cope D Coyne P Davis K Dworkin R Erdek M Finnerup N ... Furlan A Gálvez R Gatchel R Ghiasi H Goodchild C Habib A Hans G Hayes K Higa K Hulsebosch C Job C Johnson R ...
Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly ... more Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly M Cope D Coyne P Davis K Dworkin R Erdek M Finnerup N ... Furlan A Gálvez R Gatchel R Ghiasi H Goodchild C Habib A Hans G Hayes K Higa K Hulsebosch C Job C Johnson R ...
Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly ... more Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly M Cope D Coyne P Davis K Dworkin R Erdek M Finnerup N ... Furlan A Gálvez R Gatchel R Ghiasi H Goodchild C Habib A Hans G Hayes K Higa K Hulsebosch C Job C Johnson R ...
Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly ... more Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly M Cope D Coyne P Davis K Dworkin R Erdek M Finnerup N ... Furlan A Gálvez R Gatchel R Ghiasi H Goodchild C Habib A Hans G Hayes K Higa K Hulsebosch C Job C Johnson R ...
The effect of nanoparticle dose on the biodistribution and pharmacokinetics of conventional PLGA ... more 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.
A scalable platform to prepare multi-functional ocular lenses is demonstrated. Using rapidly diss... more A scalable platform to prepare multi-functional ocular lenses is demonstrated. Using rapidly dissolving polyvinylpyrrolidone (PVP) as the active stabilizing matrix, both sides of ocular lenses were coated using a modified scaled-up masking electrohydrodynamic atomization (EHDA) technique (flow rates variable between 5 and 10 µL/min, applied voltage 4-11 kV). Each side was coated (using a specially designed flip-able well) selectively with a pre-determined morphology and model drug substance. PVP nanoparticles (inner side, to be in contact with the cornea, mean size <ca.100 nm) were encapsulated with a probe (flourescein dye) and PVP nanofibres (outer side, to be exposed to air and eye lid, mean width size <ca.200 nm) were encapsulated with chloramphenicol (5 w/w% PVP). Release of the probe and anti-microbial activity (using Staphylococcus aureus NCTC 6571) were demonstrated based on rapid dissolution and contact of PVP model substance matrix. Adapting these findings further fo...
To synthesize pegylated stoichiometrically and structurally well-defined conjugates of fullerene ... more To synthesize pegylated stoichiometrically and structurally well-defined conjugates of fullerene (C60) with doxorubicin (DOX) and investigate their antiproliferative effect against cancer cell lines. Stoichiometric (1:1 and 1:2) pegylated conjugates of C60 with DOX were synthesized using the Prato reaction to create fulleropyrrolidines equipped with a carboxyl function for anchoring a polyethylene glycol (PEG) moiety and either a hydroxyl group for attaching one molecule of DOX or a terminal alkyne group for attaching two molecules of DOX through a click reaction. In both conjugates, the DOX moieties are held through a urethane-type bond. Drug release was studied in phosphate buffer (PBS, pH 7.4) and MCF-7 cancer cells lysate. The uptake of the conjugates by MCF-7 cancer cells and their intracellular localization were studied with fluorescence microscopy. The antiproliferative activity of the conjugates was investigated using the WST-1 test. One or two DOX molecules were anchored on pegylated C60 particles to form DOX-C60-PEG conjugates. Drug liberation from the conjugates was significantly accelerated in the presence of tumor cell lysate compared to PBS. The conjugates could be internalized by MCF-7 cells. DOX from the conjugates exhibited much delayed, compared to free DOX, localization in the nucleus and antiproliferative activity. Pegylated DOX-C60 conjugates (1:1) and (2:1) with well-defined structure were successfully synthesized and found to exhibit comparable, but with a delayed onset, antiproliferative activity with free DOX against MCF-7 cancer cells. The results obtained justify further investigation of the potential of these conjugates as anticancer nanomedicines.
ABSTRACT We investigated the behavior of the pH and thermo-responsive poly(2-(diethylamino)ethyl ... more ABSTRACT We investigated the behavior of the pH and thermo-responsive poly(2-(diethylamino)ethyl methacrylate-co-methacrylic acid)-b-(ethylene glycolmethylether methacrylate)-b-poly(2-(diethylamino)ethyl methacrylate-co-methacrylic acid) (P(DEAEMA-co-MAA)-b-PEGMA-b-P(DEAEMA-co-MAA)) triblock terpolymers in aqueous solution by means of static and dynamic light scattering, transmission electron microscopy and rheology. Association phenomena were observed at the isoelectric point region of the polyampholyte outer blocks leading to flower-like micelles and at higher polymer concentrations, to a three dimensional transient micellar network, exhibiting a compex thermo-response thanks to the thermo-sensitivity of the PEGMA middle block. Doxorubicin (DOX) drug was loaded in the terpolymer micelles and drug release studies were performed. Controlled drug delivery could be achieved by tuning pH. The terpolymer micelles exhibited satisfactory cytocompatibility towards human umbilical vein endothelial cells.
Purpose of the study was to develop and assess a novel controlled drug delivery system of latanop... more Purpose of the study was to develop and assess a novel controlled drug delivery system of latanoprost acid (LA). Poly(lactide)/Monomethoxy-poly(ethyleneglycol) (PLA-PEG) nanoparticles (NPs) were prepared using an emulsification-solvent evaporation technique. NPs were characterized in vitro according to their size, z-potential, drug entrapment efficiency and LA release. LA-loaded NPs (equivalent to 8.5 mg LA) were administered into the subconjunctival space of normotensive rabbits (group A). A free LA solution of the same drug content was subconjunctivally injected in a second rabbit group (group B), while blank NPs were administered in a third group (group C). A group of untreated animals (group D) served as the control. Intraocular pressure (IOP) was monitored for 8 consecutive days, using the Tono-pen XL. Aqueous humor (AH) levels of LA were evaluated for 6 days post-administration, by means of HPLC. Mean nanoparticle size was 80 nm. The drug entrapment efficiency was 18.3%. NPs sustained the release of LA over several days in vitro. Non-significant differences in baseline IOP were found between groups (p ¼ 0.22). LA-loaded NPs exerted a significant hypotensive effect on group A, while IOP values remained significantly lower compared to the rest groups, throughout the study (p ¼ 0.04). LA AH concentrations in group B continuously decreased with time, while LA levels in group A steadily increased. On day 6, LA levels were higher in group A compared to group B (344 AE 73.5 ng/ml and 228 AE 41.01 ng/ml, respectively). No adverse effects were observed. In conclusion, after subconjunctival administration, the LAloaded NPs provided sustained LA delivery in vivo. They appear to be a promising system for the controlled subconjunctival delivery of LA.
the effectiveness of the drug (Allcock,1990). The properties of macromelecular drugs have been ex... more the effectiveness of the drug (Allcock,1990). The properties of macromelecular drugs have been exploited to reduce the side effects of the antitumour agent (NH3) 2 PtC12. Kidney damage, caused by the readily excreted drug, can be reduced by its reaction with poly(bis-methylaminophosphazene), in which a non-excretable coordination complex is formed (Allen et al., 1977).
The objective of this investigation was to explore the effects of drug solubility on the evolutio... more The objective of this investigation was to explore the effects of drug solubility on the evolution of matrix dimensions and gel layer's during drug release and investigate the relationship between these effects and the mechanism and the rate of drug release. Two hydrophilic swellable polymers Polyox (POL) and cross-linked Carbopol (CARB) were employed as carriers. Caffeine (CAF) and theophylline (THE), two drugs having similar chemical structure but different aqueous solubility, were used as model drugs. Both drug and polymer characteristics were found to influence the dimensional changes of matrices and the development of the gel layer formed around the glassy core. The dimensional expansion in CAF matrices was always more pronounced than the THE matrices. Also the CARB matrices demonstrated greater maximum expansion and lower drug release than the POL matrices, due to a smaller degree of erosion of CARB. The dimensions of CARB/CAF matrices, unlike all the other matrices studied, exhibited a biphasic increase at early times, which was attributed to the cross-linked structure of CARB and the high solubility of CAF. With both polymers, a thinner gel layer was developed in the matrices containing the less soluble THE compared to the CAF matrices. The thickness of the gel layer increased continuously with time in the CAF matrices whereas it increased initially and after reaching a maximum started to decrease in THE matrices. All formulations except those of CARB/THE exhibited burst release, which depended on drug and polymer characteristics. The gel layer thickness and erosion rate appeared to determine the rate of drug release from the CARB and POL formulations. The results clearly indicate that for these matrices gel thickness and fluctuation of gel thickness affect the release rate/h of drug proportionally. Analysis of the release kinetics indicated that CAF was released mainly through diffusion whereas, THE was released mainly through matrix erosion.
Abstract Spray dried poly(lactide-co-glycolide) powders were used to prepare phenobarbitone matri... more Abstract Spray dried poly(lactide-co-glycolide) powders were used to prepare phenobarbitone matrix tablets. The release of phenobarbitone was significantly sustained, indicating the suitability of using poly(lactide-co-glycolide) matrix tablets for long-term controlled drug delivery. Drug release profiles consisted of three regions: there were an initial region of relatively high release rate (burst effect), followed by an extended region of lower and essentially constant release rate from approx. 20 to 80% of drug release. This steady state release region was followed by a final one in which the rate of drug release fell off as exhaustion of the drug in the matrix approached. A composite mechanism of drug release is proposed involving diffusion of the drug through water-filled pores in the matrix and drug diffusion through the swollen polymer. The rate of drug release increased with an increase in the glycolide content of the polymers. Decreasing the polymer molecular weight caused initially an increase but later a decrease in the release rate. These results are discussed in terms of degradation, water uptake and swelling of the polymers upon immersion in aqueous media.
Abstract A spray drying technique was adopted to prepare poly(lactide-co-glycolide) powders. Sign... more Abstract A spray drying technique was adopted to prepare poly(lactide-co-glycolide) powders. Significant difficulties were encountered with the relatively high molecular weight polymers, the spray drying of which produced threads rather than particles, unless very dilute solutions were used (less than 2% w/v). The important factor for the successful ‘spray powdering’ of poly(lactide-co-glycolide) polymers appeared to be the molecular weight of the polymer and not the viscosity of the sprayed solution. The spray dried particles were porous, almost spherical agglomerates of tiny spheres. The agglomerated and rather loose texture of the particles probably enhanced the powder compressibility. Soft and ductile powders were obtained with yield pressure values ranging from 28 to 33 MPa. No correlation was found between polymer properties and yield pressure. The contact angle values between polymer compacts and water were in the range of 72–78°, indicating a moderate polymer hydrophobicity. The molecular weight of the polymers did not have any effect on the contact angle value, whereas an increase in glycolide content tended to lower the contact angle. Water uptake by poly(lactide-co-glycolide) matrices increased steadily as matrix hydrophobicity increased with time due to polymer degradation. The weight of the matrix increased with time but, when mass loss due to degradation outweighed the gain from water absorption, the weight of the matrix began to fall. An increase in glycolide content or a decrease in polymer molecular weight caused an increase in both the percent water uptake rate. The polymers swelled considerably, although they absorbed relatively small amounts of water and this may have significant implications for drug release from poly(lactide-co-glycolide) matrix tablets.
The physicochemical properties, the colloidal stability in vitro and the biodistribution properti... more 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.
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, Jan 24, 2015
To investigate the application of water-dispersible poly(lactide)-poly(ethylene glycol) (PLA-PEG)... more To investigate the application of water-dispersible poly(lactide)-poly(ethylene glycol) (PLA-PEG) copolymers for the stabilization of graphene oxide (GO) aqueous dispersions and the feasibility of using the PLA-PEG stabilized GO as a delivery system for the potent anticancer agent paclitaxel. A modified Staudenmaier method was applied to synthesize graphene oxide (GO). Diblock PLA-PEG copolymers were synthesized by ring-opening polymerization of dl-lactide in the presence of monomethoxy-poly(ethylene glycol) (mPEG). Probe sonication in the presence of PLA-PEG copolymers was applied in order to reduce the hydrodynamic diameter of GO to the nano-size range according to dynamic light scattering (DLS) and obtain nano-graphene oxide (NGO) composites with PLA-PEG. The composites were characterized by atomic force microscopy (AFM), thermogravimetric analysis (TGA), and DLS. The colloidal stability of the composites was evaluated by recording the size of the composite particles with time an...
Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly ... more Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly M Cope D Coyne P Davis K Dworkin R Erdek M Finnerup N ... Furlan A Gálvez R Gatchel R Ghiasi H Goodchild C Habib A Hans G Hayes K Higa K Hulsebosch C Job C Johnson R ...
Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly ... more Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly M Cope D Coyne P Davis K Dworkin R Erdek M Finnerup N ... Furlan A Gálvez R Gatchel R Ghiasi H Goodchild C Habib A Hans G Hayes K Higa K Hulsebosch C Job C Johnson R ...
Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly ... more Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly M Cope D Coyne P Davis K Dworkin R Erdek M Finnerup N ... Furlan A Gálvez R Gatchel R Ghiasi H Goodchild C Habib A Hans G Hayes K Higa K Hulsebosch C Job C Johnson R ...
Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly ... more Atchison J Aurilio C Baastrup C Barbarisi M Baron R Brett B Canavero S Coates B Cohrs R Connolly M Cope D Coyne P Davis K Dworkin R Erdek M Finnerup N ... Furlan A Gálvez R Gatchel R Ghiasi H Goodchild C Habib A Hans G Hayes K Higa K Hulsebosch C Job C Johnson R ...
The effect of nanoparticle dose on the biodistribution and pharmacokinetics of conventional PLGA ... more 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.
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Papers by K Avgoustakis