In Vitro Evaluation of Polyisobutylcyanoacrylate Nanoparticles as a Controlled Drug Carrier for Theophylline

Abstract

Theophylline nanoparticles were prepared by emulsifier-free emulsion polymerization technique in continuos aqueous phase. The polymerization process was carried out at a pH 3. Different concentrations of isobutylcyacoacrylate (IBCA) were used to investigate the effect of monomer concentration. The in vitro release of theophylline in phosphate buffer was studied. An HPLC assay was used to follow the release of the drug from the nanospheres. This polymerization technique was able to hold 2349% of the drug initially dissolved in the aqueous medium. The percentage drug loading is a monomer concentration dependent. Increasing the monomer concentration above 40 μL per mL resulted in a less significant increase in the percentage drug loading. The percentage of drug retained in nanospheres up to 24 hr followed first order kinetics (r = 0.94-0.98). The release rate constant of theophylline from nanoparticles is inversely related to the monomer concentration in the initial solution (r = 0.996). In the mean time the release rate constant of theophylline from the nanoparticles was directly related to the amount of the drug added initially (r = 0.990).     

Poly(lactide-co-glycolide)-methoxy-poly(ethylene glycol) nanoparticles: drug loading and release properties

In this work, the drug loading and in vitro release properties of PLGA-mPEG nanoparticles were studied. Three methyl-xanthine derivatives differing significantly in aqueous solubility, i.e., caffeine, theophylline, and theobromine, were employed as model drugs. Two different PLGA-mPEG copolymer compositions, namely PLGA(40)mPEG(5) and PLGA(136)mPEG(5), were included in the study. The nanoparticles were prepared by a double emulsion technique. The drug release properties of the nanoparticles in phosphate buffered saline (PBS) and in human plasma were determined. An increase of the drug proportion in the feed led to increased drug loading. The composition of the PLGA-mPEG copolymer (PLGA/mPEG molar ratio) did not appear to affect drug loading and encapsulation. Caffeine exhibited higher loading in the nanoparticles than theobromine and this exhibited a little higher loading than theophylline. Solid-state solubility of the drug in PLGA-mPEG did not affect drug loading. Drug loading and encapsulation in the PLGA-mPEG nanoparticles appeared to be governed by the partition coefficient of the drug between the organic phase and the external aqueous phase employed in nanoparticle preparation. Relatively low loading and encapsulation values were obtained, suggesting that the physical entrapment of drugs in PLGA-mPEG nanoparticles could only be an option in the development of formulations of potent drugs. Only the release of the least water-soluble theobromine was efficiently sustained by its entrapment in the nanoparticles, indicating that the physical entrapment of drugs provides the means for the development of controlled-release PLGA-mPEG nanoparticulate formulations only in the case of drugs with low aqueous solubility.     

Interfacial Polymerization, A Useful Method for the Preparation of Polymethylcyanoacrylate Nanoparticles

An interfacial polymerization procedure was developed for the preparation of polymethylcyanoacrylate (PMCA) nanoparticles loaded with triamcinolone acetonide. The nanoparticles were characterized concerning their interior structure, size distribution, drug content, drug release and in vivo distribution. These results (except those for the in vivo distribution) were compared with those obtained with nanoparticles prepared by micell polymerization [5]. Both preparation procedures yielded particles with a mean diameter below 500 nm. The drug content of the nanoparticles prepared by interfacial polymerization ranged from 6,5% w/w to 1,9% w/w depending on the employed monomer concentration in contrast to 0,045% w/w for nanoparticles prepared by micell polymerization [5]. In comparison to microcrystalline substance the drug release from the nanoparticles could be sustained in all cases, but there was no difference in drug release between the nanoparticles prepared by both methods.

After removal of surface adherent drug from nanoparticles prepared by both methods those prepared by interfacial polymerization had an about 12 times higher drug content and the remaining drug amount was released more slowly by these particles. Furthermore, using increasing monomer concentrations during interfacial polymerization (125 - 500 mg/100 ml emulsion) drug release was slowed down, but no further improvement could be achieved for monomer concentrations exceeding 250 mg/100 ml emulsion.

After intravenous injection of ^99mTc labeled PMCA nanoparticles into rats they accumulated predominantly in liver, spleen and kidney, a distribution pattern usually found for colloidal particles.     

Enhancement of absorption of insulin-loaded polyisobutylcyanoacrylate nanospheres by sodium cholate after oral and subcutaneous administration in diabetic rats.

Polyisobutylcyanoacrylate (PIBCA) nanospheres were employed as biodegradable polymeric carriers for oral (p.o.) and subcutaneous (s.c.) delivery of insulin. The polymerization technique used was able to hold 65%-95% of insulin added 30 min after initiation of polymerization. The percentage drug loading was monomer concentration dependent. Insulin adsorption to the nanospheres was measured by radioimmunoassay. Although Pluronic F68 (0.5%) did not significantly alter the in vitro insulin degradation half-life T50%, sodium cholate (0.5%) increased the degradation T50% of insulin by 56% (from 13.6 +/- 1.6 to 22.1 +/- 2 min). This study also investigated the in vivo performance of insulin-loaded PIBCA in aqueous suspension with or without sodium cholate (0.5%) and Pluronic F68 (0.5%) surfactants after oral and subcutaneous administration to alloxan-induced diabetic rats. Insulin absorption was evaluated by its hypoglycemic effect. Insulin associated with PIBCA nanospheres retains its biological activity up to 15 h and 24 h after oral and subcutaneous administrations, respectively. Administered orally insulin-loaded (75 U/kg) nanospheres, in the presence of surfactants, significantly reduced the mean blood glucose level from 392 +/- 32 to 80 +/- 13 mg/dl within 2 h and maintained it at 100 mg/dl or less for more than 8 h. On the other hand, the subcutaneous administration of insulin-loaded (25 U/kg) nanospheres significantly decreased the blood glucose level from 406 +/- 33 to 88.5 +/- 12.8 mg/dl within 1 h, and the lowered glucose level was maintained at 100 mg/dl or less for more than 12 h; it returned to its initial value 24 h after administration. Insulin-loaded nanospheres with surfactants showed significant (P < .05) pharmacological availability (PA%) of 37.6% +/- 3.7% and 65.2% +/- 2.7% after oral and subcutaneous dosages, respectively. The existence of surfactants with PIBCA nanospheres improved the oral PA% by 49.2%. These findings suggest that the developed PIBCA, in the presence of surfactants, would be useful not only in improving insulin gastrointestinal absorption, but also in sustaining its systemic action by lowering the blood glucose to an acceptable level.     

Enhanced oral bioavailability of 10-hydroxycamptothecin through the use of poly (n-butyl cyanoacrylate) nanospheres

The article describes the preparation, physicochemical characterization, drug release, and in vivo behavior of 10-hydroxycamptothecin-loaded poly (n-butyl cyanoacrylate) (PBCA) nanospheres (HCPT-PBCA-NSs). HCPT-PBCA-NSs were successfully prepared via emulsion polymerization of n-butyl cyanoacrylate (BCA) monomer in acidic medium with the aid of two colloidal stabilizers (Poloxamer 188 and Dextran 70). The influence of pH, the time of polymerization, and the dosage of the drug on particle size and encapsulation efficiency (EE) were studied. HCPT-PBCA-NSs were of spherical shape and uniformly dispersed with a particle size of 135.7?nm, and zeta potential of ?18.18?mV. EE, drug loading (DL), and yield of HCPT-PBCA-NSs were 51.52, 0.63, and 88.25%, respectively. FTIR, ¹H NMR, and DSC showed complete polymerization of BCA monomer and HCPT existed in the form of molecular or amorphous in NSs. In vitro release of the drug from HCPT-PBCA-NSs exhibited sustained-release behavior with an initial burst release and about 60% of HCPT was released from the formulation within 24?h of dialysis. The pharmacokinetic study in healthy rats after oral administration showed that encapsulation of HCPT into PBCA-NSs increased the C_max about 3.84 times and increased AUC_0?t about 5.40 times compared with that of HCPT suspension. It was concluded that PBCA-NSs could be a promising drug carrier to load HCPT for oral drug delivery if efforts are made in the future to improve its poor DL capacity.     

Synthesis and characterization of paclitaxel-imprinted nanoparticles for recognition and controlled release of an anticancer drug

Imprinted nanoparticles as drug delivery carriers have been considered because owing to their cross-linked network, they act as the drug reservoir for controlled release. In this study, selective MIPs nanoparticles of paclitaxel (PTX) were successfully developed for application in the biological molecular recognition and in the design of new anticancer drug delivery systems. The MIPs nanoparticles prepared by miniemulsion polymerization technique using methacrylic acid (MAA) and methyl methacrylate as non-covalent functional monomer, ethylene glycol dimethacrylate and trimethylolpropane trimethacrylate (TRIM) as cross-linker agent, azobisisobutyronitrile as initiator, and hexadecane as hydrophobic agent. In order to prepare of MIP nanoparticles, the synthesis conditions and effective parameters, such as: cross-linker agent, different molar ratios of template–functional monomer–cross-linker agent, were investigated. In addition, the effect of different molar ratios of template and monomers on polymers binding and morphology were characterized. Structure and thermal properties of MIPs were confirmed by FT-IR spectroscopy and thermogravimetric analysis. Imprinted nanoparticles showed significant drug loading and encapsulation efficiency, 17.8 and 100 %, respectively. The particle size of MIP nanoparticles varies between 187 and 726 nm, according the SEM images and laser light scattering data. The imprinted nanoparticles showed satisfactory affinity (84 %) to PTX with a binding of 12 times higher than non-imprinted nanoparticles in biological samples when MAA and TRIM were used as functional and cross-linker monomer, respectively. Results from release experiments of MIPs showed a very slow and controlled release of PTX which would be helpful for sustained drug delivery.     

Possibility for the development of cosmetics with PLGA nanospheres

The optimized preparation of Poly–(lactide-co-glycolic acid) (PLGA) nanospheres containing ubiquinone (UQ) for cosmetic products was pursued. By investigating various conditions for the preparation of UQ/PLGA nanospheres such as the molecular weight of PLGA, PLGA concentration, and UQ concentration, UQ/PLGA nanospheres with increased stability and slower drug release at a higher drug loading efficiency were prepared. Permeation tests on the prepared nanospheres using iontophoresis via electric dermal administration on membrane filters (200?nm pore size) and hairless mouse skin samples were also carried out. After iontophoresis, the nanospheres choked the membrane filter and remained on the horny layer of the hairless mouse skin, even after washing. Therefore, the prepared UQ/PLGA nanospheres and the established iontophoresis technique with the PLGA nanospheres in the present study can be applied to the future development of cosmetics.     

Platinum-nanoparticle-supported core--shell polymer nanospheres with unexpected water stability and facile further modification

Core-shell nanospheres (CSNSs) with hydrophobic cores and hydrophilic shells were fabricated via a simple mini-emulsion polymerization for the stabilization of platinum nanoparticles (Pt-NPs). The CSNSs showed extremely high loading capacity of Pt-NPs (the largest loading amount of the Pt-NPs was about 49.2 wt%). Importantly, the Pt-NPs/CSNSs nanocomposites had unexpected stability in aqueous solution. DLS results revealed that the CSNSs loaded with Pt-NPs exhibited almost no aggregation after standing for a long time . However, the Pt-NPs immobilized on the CSNSs were not straitlaced: they could transport and redistribute between CSNSs freely when the environmental temperature was higher than the melting point of the CSNS shell. Owing to their excellent stability in aqueous solution, the surface of the Pt-NPs/CSNSs nanocomposites could be further decorated easily. For example, polyaniline (PANI)-coated Pt-NPs/CSNSs, nickel (Ni)-coated Pt-NPs/CSNSs and PANI/Pt-NPs dual-layer hollow nanospheres were facilely fabricated from the Pt-NPs/CSNS nanocomposites.     

Facile synthesis of monodisperse superparamagnetic Fe3O4/PMMA composite nanospheres with high magnetization

Monodisperse superparamagnetic Fe(3)O(4)/polymethyl methacrylate (PMMA) composite nanospheres with high saturation magnetization were successfully prepared by a facile novel miniemulsion polymerization method. The ferrofluid, MMA monomer and surfactants were co-sonicated and emulsified to form stable miniemulsion for polymerization. The samples were characterized by DLS, TEM, FTIR, XRD, TGA and VSM. The diameter of the Fe(3)O(4)/PMMA composite nanospheres by DLS was close to 90 nm with corresponding polydispersity index (PDI) as small as 0.099, which indicated that the nanospheres have excellent homogeneity in aqueous medium. The TEM results implied that the Fe(3)O(4)/PMMA composite nanospheres had a perfect core-shell structure with about 3 nm thin PMMA shells, and the core was composed of many homogeneous and closely packed Fe(3)O(4) nanoparticles. VSM and TGA showed that the Fe(3)O(4)/PMMA composite nanospheres with at least 65% high magnetite content were superparamagnetic, and the saturation magnetization was as high as around 39 emu g(-1) (total mass), which was only decreased by 17% compared with the initial bare Fe(3)O(4) nanoparticles.     

Study of biodistribution of methotrexate-loaded bovine serum albumin nanospheres in mice

Nanospheres made from natural hydrophilic polymers have been proved efficient in terms of better drug-loading capacity, biocompatibility, and possibility less opsonization by reticuloendothelial system (RES) through an aqueous stearic barrier. Hence, nanospheres containing methotrexate were prepared from bovine serum albumin (BSA) by a novel pH coacervation method. A drug-to-polymer ratio study was carried out to determine the carrier capacity. The batch with the highest drug loading was subjected to in vitro analysis. It was found to provide a slow release after an initial burst release. Biodistribution of nanosphere-bound drug was compared with that of free drug in mice. It was observed that the percentage increase in drug distribution to the lungs, liver, and spleen was markedly high from the nanosphere when compared to free drug.     

Study of Biodistribution of Methotrexate-Loaded Bovine Serum Albumin Nanospheres in Mice

Nanospheres made from natural hydrophilic polymers have been proved efficient in terms of better drug-loading capacity, biocompatibility, and possibility less opsonization by reticuloendothelial system (RES) through an aqueous stearic barrier. Hence, nanospheres containing methotrexate were prepared from bovine serum albumin (BSA) by a novel pH coacervation method. A drug-to-polymer ratio study was carried out to determine the carrier capacity. The batch with the highest drug loading was subjected to in vitro analysis. It was found to provide a slow release after an initial burst release. Biodistribution of nanosphere-bound drug was compared with that of free drug in mice. It was observed that the percentage increase in drug distribution to the lungs, liver, and spleen was markedly high from the nanosphere when compared to free drug.     

Molecularly imprinted nanoparticles prepared by miniemulsion polymerization as selective receptors and new carriers for the sustained release of carbamazepine

Water-compatible imprinted nanoparticles were prepared for carbamazepine as a template and used for the selective extraction and controlled release of carbamazepine. Assay materials and drug delivery carriers were typically used in aqueous environments, so it is generally preferable to prepare solvent-free molecularly imprinted nanoparticles in water using the miniemulsion polymerization method. The present work investigates a bio-analytical strategy generically applicable to imprinted materials for molecular recognition studies, including equilibrium and non-equilibrium binding, and release experiments, increasing the knowledge of the molecular interactions between the template molecules and imprinted nanoparticles. The results showed that the imprinted nanoparticles exhibited a higher binding level and slower release rate than non-imprinted nanoparticles. The selectivity of imprinted nanoparticles for carbamazepine studied in comparison with an analogue compound, oxcarbazepine, the main metabolite of carbamazepine. The recovery and selectivity of carbamazepine in human serum was determined to be 100%, 1.7 times that of oxcarbazepine. The results indicated that carbamazepine-imprinted nanoparticles are appropriate for serum level determination of the drug in therapeutic range. The template to functional monomer ratio as a key factor controlling the recognition and release kinetic mechanism of imprinted nanoparticles is discussed. The imprinted nanoparticles prepared at the appropriate template to functional monomer mole ratio (2:8) exhibited the best drug affinity (5.1 times higher) and a slower drug release rate due to the interaction of carbamazepine with the imprinted cavities within the nanoparticles. Loaded imprinted nanoparticles as drug reservoirs were able to prolong carbamazepine release, in 1% wt sodium dodecyl sulfate aqueous solution, for more than 8 days.     

Enhancement of Absorption of Insulin-Loaded Polyisobutylcyanoacrylate Nanospheres by Sodium Cholate After Oral and Subcutaneous Administration in Diabetic Rats

Polyisobutylcyanoacrylate (PIBCA) nanospheres were employed as biodegradable polymeric carriers for oral (p.o.) and subcutaneous (s.c.) delivery of insulin. The polymerization technique used was able to hold 65%–95% of insulin added 30 min after initiation of polymerization. The percentage drug loading was monomer concentration dependent. Insulin adsorption to the nanospheres was measured by radioimmumoassay. Although Pluronic F68 (0.5%) did not significantly alter the in vitro insulin degradation half-life T_50%, sodium cholate (0.5%) increased the degradation T_50% of insulin by 56% (from 13.6 ± 1.6 to 22.1 ± 2 min). This study also investigated the in vivo performance of insulin-loaded PIBCA in aqueous suspension with or without sodium cholate (0.5%) and Pluronic F68 (0.5%) surfactants after oral and subcutaneous administration to alloxan-induced diabetic rats. Insulin absorption was evaluated by its hypoglycemic effect. Insulin associated with PIBCA nanospheres retains its biological activity up to 15 h and 24 h after oral and subcutaneous administrations, respectively. Administered orally, insulin-loaded (75 U/kg) nanospheres, in the presence of surfactants, significantly reduced the mean blood glucose level from 392 ± 32 to 80 ± 13 mg/dl within 2 h and maintained it at 100 mg/dl or less for more than 8 h. On the other hand, the subcutaneous administration of insulin-loaded (25 U/kg) nanospheres significantly decreased the blood glucose level from 406 ± 33 to 88.5 ± 12.8 mg/dl within 1 h, and the lowered glucose level was maintained at 100 mg/dl or less for more than 12 h; it returned to its initial value 24 h after administration. Insulin-loaded nanospheres with surfactants showed significant P < 05) pharmacological availability (PA%) of 37.6% ± 3.7% and 65.2% ± 2.7% after oral and subcutaneous dosages, respectively. The existence of surfactants with PIBCA nanospheres improved the oral PA% by 49.2%. These findings suggest that the developed PIBCA, in the presence of surfactants, would be useful not only in improving insulin gastrointestinal absorption, but also in sustaining its systemic action by lowering the blood glucose to an acceptable level.     

Development and In-Vitro Evaluation of a Multiparticulate Sustained Release Theophylline Formulation

A multiparticulate sustained release formulation of theophylline was developed and evaluated in-vitro. The formulation comprised spherical pellets of high drug loading, coated with a rate controlling membrane. The pellets were prepared using an extrusion spheronisation method, whilst coating was performed with an aqueous dispersion of ethylcellulose using a fluidized bed coating technique. When ethylcellulose was used alone as the coating polymer, the drug release profile was unsatisfactory, but could be improved by incorporating a coating additive. Several additives were evaluated and methylcellulose of high Viscosity grade was found most satisfactory. The in-vitro theophylline release was relatively linear and pH independent, and could be varied in a predictable manner by manipulating the coat thickness. In addition, when the coated pellets were subjected to additional thermal treatment, the drug release was stable after storage for one year.     

Influence of Drug Loading and Gel Structure on in-Vitro Release Kinetics from Photopolymerized Gels

Precious work has shown that stabls and homogenous poly HEMA gels can be prepared using a visible light sensitive initiator system. Gels were prepared from solutions of water and poly-2-hydroxyethyl methacrylate monomer. At concentrations of water greater than 10% v/v, translucent gel resulted. However, polymerization solvents such as glycerol and tertiary butyl alcohol (T.B.T.A) gave transparent, flexible gels over a wider range of concentrations. Subsequent work showed that changes in polymerization solvent and monomer concentration brought about changes in the mechanical and structural properties of the gels.

In this work, the effects of drug loading and polymerization solvents on in vitro drug release rate from the photopolymerized polyHEMA gels were studied. Polymerization solvents used included glycerol and tertiary butyl alcohol. Results indicated that the release rate in vitro was a diffusion-controlled process except at high drug concentrations in poly HEMA - T.B.T.A. gels when a departure from root-time kinetics occurred. Poly HEMA T.B.T.A. gels presented greater hindeirance to the mobility of the drug than polyHEMA - glycerol gels. Higuch's model for release from incoluble homogenous matrices containing dispersed solute was found to be inappropriate for the analysis of the release of the drug from the gels. A simple equation based on the modelling of desorption in diffusion was found more appropriate. Estimates of drug release rates in vitro may be made from measurements of the physical crosslinking density of the polymer (if matrix-diffusion controlled release is operative). Quantitative drug loading was achieved in the gels as evidenced from variation in crosslinking density and in vitro release rate with drug loading.     

Physico-chemical properties investigation of cisplatin loaded polybutyladipate (PBA) nanoparticles prepared by w/o/w

cis-Diamminedichloroplatinum(II) (cisplatin) is used against different kinds of cancers. Unfortunately, because of the severe side-effects like nephrotoxicity, ototoxicity, etc., they are administered in small doses at low concentrations. The purpose of this work is to improve injectional controlled release (ICR) of cisplatin that releases drug in the extended temporal periods. In order to access this aim, biodegradable polymeric nanoparticles containing cisplatin as anticancer drug of various ranges from 71 to 661 nm were prepared by a w/o/w double emulsion solvent evaporation technique. Influences of process parameters such as solvent removal technique, type and concentration of polymer, volume of oil phase, volume of external aqueous phase, concentration of stabilizer, drug concentration in the internal and external aqueous phases and power of sonication on morphology, characteristics of the nanoparticles and release profile were investigated. Morphology of the nanoparticles was studied by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) and the images indicated that spherical shape of the nanoparticles can be tailored to rod-like shape by changing the reaction parameters. Size of the nanoparticles decreased as polymer concentration decreases. Volume of oil phase, power of sonication and drug concentration in the internal water phase affected the size of nanoparticles. Drug release profiles indicate that polymer concentration in the oil phase and stabilizer concentration in the external water phase have critical role in the drug release process from the nanoparticles. The in-vitro release of the encapsulated drug was observed by using the diffusion models of release from a sphere carrier and the release pattern was shown to be a complex process.     

Preparation and Preliminary Evaluation of Eudragit RL and RS Pseudolatices for Controlled Drug Release

Eudragit RL and RS pseudolatices were prepared by the solvent change technique, which consisted of dissolving the polymer in a water miscible organic solvent or in a mixed water miscible organic solvent system, followed by dispersian in deionized water under mild agitation. The organic solvent (s) was removed from the aqueous organic solution to leave a stable Eudragit latex.

Eudragit pseudolatex coated theophylline pellets were prepared in a fluidized-bed coating machine. The effects of polymer type and coating level, plasticizer concentration, and PH of the dissolution medium on drug release were investigated. The higher content of quaternary ammonium groups attached to the polymer backbone make the coatings produced from Eudragit RL too water sensitive; and hence unsuitable for controlling theophylline release. On the other hand, Eudragit RS films retarded theophylline release. On the other hand, Eudragit RS films retarded theophylline release over a wide pH range. Release of the drug was found to be a function of the polymer coating level, plasticizer concentration and dependent on pH of the dissolution medium.     

Synthesis of biocompatible, mesoporous Fe(3)O(4) nano/microspheres with large surface area for magnetic resonance imaging and therapeutic applications

This article reports the fabrication of mesoporous Fe(3)O(4) nano/microspheres with a high surface area value (163 m(2)/g, Brunauer-Emmett-Teller) and demonstrates their use for drug loading, release, and magnetic resonance imaging (MRI). These monodispersed, mesoporous Fe(3)O(4) nano/microspheres with controllable average sizes ranging from 50 to 200 nm were synthesized using a Fe(3)O(4)/poly(acrylic acid) hybrid sphere template and subsequent silica shell formation and removal. We found that the SiO(2) coating is a crucial step for the successful synthesis of uniform mesoporous Fe(3)O(4) nano/microspheres. The as-synthesized mesoporous Fe(3)O(4) nanospheres show a high magnetic saturation value (M(s) = 48.6 emu/g) and could be used as MRI contrast agents (r(2) = 36.3 s(-1) mM(-1)). Trypan blue exclusion and MTT assay (see Supporting Information ) cytotoxicity analyses of the nanospheres based on HepG2 and MDCK cells showed that the products were biocompatible, with a lower toxicity than lipofectamine (positive control). Hydrophilic ibuprofen and hydrophobic zinc(II) phthalocyanine drug loading into mesoporous Fe(3)O(4) nanospheres and selected release experiments were successfully achieved. The potential use of mesoporous Fe(3)O(4) nanospheres in biomedical applications, in light of the nano/microspheres' efficient drug loading and release, MRI, and low cytotoxicity, has been demonstrated. It is envisaged that mesoporous Fe(3)O(4) nanospheres can be used as drug carriers and MRI contrast agents for the reticuloendothelial system; they can also be delivered locally, such as via a selective catheter.     

Influence of Drug Loading and Gel Structure on in-Vitro Release Kinetics from Photopolymerized Gels

Abstract

Precious work has shown that stabls and homogenous poly HEMA gels can be prepared using a visible light sensitive initiator system. Gels were prepared from solutions of water and poly-2-hydroxyethyl methacrylate monomer. At concentrations of water greater than 10% v/v, translucent gel resulted. However, polymerization solvents such as glycerol and tertiary butyl alcohol (T.B.T.A) gave transparent, flexible gels over a wider range of concentrations. Subsequent work showed that changes in polymerization solvent and monomer concentration brought about changes in the mechanical and structural properties of the gels.

In this work, the effects of drug loading and polymerization solvents on in vitro drug release rate from the photopolymerized polyHEMA gels were studied. Polymerization solvents used included glycerol and tertiary butyl alcohol. Results indicated that the release rate in vitro was a diffusion-controlled process except at high drug concentrations in poly HEMA - T.B.T.A. gels when a departure from root-time kinetics occurred. Poly HEMA T.B.T.A. gels presented greater hindeirance to the mobility of the drug than polyHEMA - glycerol gels. Higuch's model for release from incoluble homogenous matrices containing dispersed solute was found to be inappropriate for the analysis of the release of the drug from the gels. A simple equation based on the modelling of desorption in diffusion was found more appropriate. Estimates of drug release rates in vitro may be made from measurements of the physical crosslinking density of the polymer (if matrix-diffusion controlled release is operative). Quantitative drug loading was achieved in the gels as evidenced from variation in crosslinking density and in vitro release rate with drug loading.     

Poly(vinyl alcohol) hydrogels as hydrophilic matrices for the release of lipophilic drugs loaded in PLGA nanoparticles

Poly(vinyl alcohol) (PVA) hydrogels prepared by a freeze-thawing procedure were evaluated as matrices for the release of water-insoluble drugs such as dexamethasone. As it is impossible to directly entrap a lipophilic drug into a hydrophilic matrix, a novel mechanism has been designed based on producing biodegradable nanoparticles loaded with the drug, that could then be entrapped into the hydrogels. Nanoparticles were prepared by a solvent evaporation technique using a biodegradable copolymer of poly(lactic acid)-poly(glycolic acid) (PLGA). The effects of several processing parameters on particle properties were investigated. The drug release from free nanoparticles was compared to that from the nanoparticles entrapped into the PVA matrices. It was observed that the release profile of the drug is not significantly affected by the PVA matrix. A correlation was found between the amount of drug released and the PVA concentration in the hydrogels: the percentage of drug released, as a function of time, decreased by increasing PVA concentration, indicating that PVA concentration can be used as a tool in modulating the release of the drug.