Journal of Bioactive and Compatible Polymers recent issues

A Polyurethane-Gelatin Hybrid Construct for Manufacturing Implantable Bioartificial Livers

Wei Xu, , Xiaohong Wang, , Yongnian Yan, , Renji Zhang, — 2008-09-04

A novel 3D hybrid construct was developed for liver manufacturing by depositing biodegradable polyurethane (PU) and a naturally derived polymer gelatin simultaneously via a double nozzle rapid prototyping (RP) technique. A grid object was produced by precisely and simultaneously dispersing the PU and gelatin to form 3D constructs with interconnected macro-channels at a low temperature (-28°C). Micro-pores were formed by freeze-drying the constructs. The PU polymer provided mechanical support while gelatin provided accommodation for implant cells. The hydrophilicity of the hybrid constructs was between the pure PU and pure gelatin structures. The interconnected channels allow nutrients and oxygen to be supplied throughout the construct as well as provide space for the attachment of cells. The design and fabrication strategies, used to create complex physical objects directly from computer aided design (CAD) models, represent a promising technique for implantable bioartificial livers. It is anticipated that these PU-gelatin hybrid constructs will serve as a useful model for bioartificial liver manufacturing.

New Multicomponent Bioerodible Electrospun Nanofibers for Dual-controlled Drug Release

Piras, A.M., Chiellini, F., Chiellini, E., Nikkola, L., Ashammakhi, N. — 2008-09-04

The objective of this study was to evaluate the bioerodible polymer poly(maleic anhydride-alt-2-methoxyethyl vinyl ether) n-butyl hemiester, for multicomponent drug-loaded nanofibers produced by electrospinning. Diclofenac sodium (DS) and human serum albumin (HSA) were used as conventional drug and biopharmaceutical models. The influence of drug loading was correlated to beads presence, morphology and fibers diameter. When DS and HSA were loaded separately, a uniform distribution within fibers and beads was observed. However, when both components were loaded simultaneously, a heterogeneous distribution of DS was observed with a prominent amount in the cylindrical beads. The in vitro drug release evaluation from these nanomaterials displayed an independent delivery of the two components. These studies support the feasibility of multicomponent, bioerodible polymeric nanofibers preparation loaded with combination of traditional drugs and proteins.

An In Situ Gel-Forming Heparin-Conjugated PLGA-PEG-PLGA Copolymer

Lih, E., Yoon Ki Joung, , Jin Woo Bae, , Ki Dong Park, — 2008-09-04

Novel heparin-conjugated PLGA-PEG-PLGA hydrogels were prepared via Michael-type addition between thiolated heparin and PLGA-PEG-PLGA diacrylate. The thiolated heparin (HP-SH) was conjugated with thiolacid dihydrazide followed by reduction. The structure and the thiol determination of obtained HP-SH were characterized by ¹H NMR and the Ellman method. Anticoagulant activity and pK_a of the HP-SH were determined by aPTT test and UV absorbance measurement which were 79.3% and 10.5, respectively. The PLGA-PEG-PLGA diacrylate was synthesized by bulk ring-opening polymerization of D,L-lactide (DLLA) and glycolide (GA) with PEG and stannous 2-ethylhexanoate, followed by the acrylation of the terminal groups. HP—SH was then conjugated to PLGA-PEG-PLGA diacrylate by Michael addition. Phase diagrams of the hydrogels were obtained by vial tilting; the release of heparin from the hydrogels exhibited temperature dependent sol—gel transition behavior. These in situ-forming heparin-conjugated hydrogels are novel as injectable and tissue-compatible scaffold formation, thermo-sensitivity, and growth factor binding.

Effects of Fungal-derived High Molecular Weight Chitosan on 5-Fluorouracil-induced Adverse Reactions

2008-09-04

The effects of fungal-derived high molecular weight chitosan (HMWC) on the prevention of 5-fluorouracil (5-FU)-induced side-effects were studied in a sarcoma-bearing mice model. 5-FU (12.5mg/kg) was gargled into the mice with or without HMWC (25, 75, and 150mg/kg) every 12 h for consecutive 8 or 16 days in different experiments. The HMWC (25—150 mg/kg) exerted no toxicity and did not interfere with the anti-tumor activity of 5-FU on sarcoma-bearing mice. HMWC in a higher dose (150 mg/kg) partially protected 5-FU-induced cytotoxicity on peripheral leukocytes, lymphocytes, and bone marrow CD-19 positive cells. HMWC reversed the 5-FU suppression of intestine sucrase activity and attenuated the 5-FU-induced diarrhea. Bone marrow cells micronucleus and DNA comet assays demonstrated that HMWC significantly reversed 5-FU-induced genome toxicity to marrow cells. These results suggested that fungal-derived HMWC attenuated the 5-FU-induced bone marrow and gastrointestinal toxicity, and has the potential for clinical applications in the future.

Syntheses and Evaluations of Antitumor and Antiangiogenic Compounds Conjugated with 5-Fluorouracil and Ascorbic Acid

Lee, S.-M., Kim, B.-G., Ha, C.-S., Chung, I., Dong Xie, — 2008-09-04

The new multifunctional antitumor conjugates containing ascorbic acid and 5-fluorouracil (5-FU) were synthesized from bicyclo[2.2.2]oct-7-ene-2,3,5,6-tetracarboxylic dianhydride, ascorbic acid and/or a chain spacer, followed by condensation with 5-FU. The synthesized conjugates were identified by ¹H and ¹³C NMR spectroscopies and elemental analysis. The in vitro cytotoxicities of these conjugates were determined and their antitumor activity was evaluated. The IC₅₀ values (drug concentration for 50% inhibition of tumor growth) indicated that the synthesized conjugates were better inhibitors against cancer cells and were lower in cytotoxicity than the free 5-FU. The in vivo antitumor activity of the conjugates was examined against mice bearing the sarcoma 180 tumor cells. The life spans (T/C) of mice treated with the conjugates were higher than for the free 5-FU. In addition, the synthesized conjugates showed excellent antiangiogenic activity, based on the embryo chorioallantoic membrane assay.

Microwave-assisted Preparation of Magnetic Albumin Microspheres

Chen, C.-Y., Qi Long, , Li, X.-H., Jiao Xu, — 2008-09-04

A new microwave-assisted method was used to prepare magnetic Fe₃ O₄ particles and magnetic bovine albumin microspheres. The microwave method produced smaller particles and is faster than traditional methods. The optimum conditions to prepare the Fe₃O₄ particles were three minutes at pH 13 and 80°C. Magnetic microspheres containing albumin were synthesized based on heating times and temperatures to form microspheres with different properties. For example, heating for 4min, at 160°C, yielded smaller sized microspheres (30 µm). Confirmed by XRD, SEM, and FT-IR that iron oxide particles were encapsulated in biocompatible proteins, The thermal stability of the microspheres were determined by DSC and TG. The magnetic properties were determined by UV—VIS spectraphotometry and a Guoy magnetic balance. This microwave process could become a preferred method for the synthesis of magnetized protein microspheres.

Pantoprazole-Na Release from Poly(acrylamide-co-crotonic acid) and Poly(acrylic acid-co-crotonic acid) Hydrogels

Pulat, M., Cetin, M. — 2008-06-03

Poly(acrylamide-co-crotonic acid) (PAAmCA), poly(acrylic acid-co-crotonic acid) (PAACA), PAA and PAAm hydrogels were prepared by free radical polymerization and ethylene glycol dimethacrylate (EGDMA) as a crosslinker. The variations of swelling values (%) with time, temperature, and pH were determined for four types of hydrogels. The PAACA hydrogel was swollen 2300% at pH = 7.4 and 37°C. The drug release from pantoprazole-Na loaded PAACA and PAAmCA hydrogels was followed at pH = 7.4, 37°C for 30 h. The release from PAACA hydrogel was faster than that from PAAmCA hydrogel; therapeutic levels for both hydrogels are obtained within 1 hour. Non-Fickian diffusion was determined for both hydrogels.

Synthesis of pH-Sensitive and Biodegradable CM-Cellulose/Chitosan Polyampholytic Hydrogels with Electron Beam Irradiation

Long Zhao, , Mitomo, H., Yosh, F. — 2008-06-03

A series of novel environment-conscious hydrogels were prepared from carboxymethylated cellulose (CM-cellulose) and chitosan using irradiation without any additives. Gel fraction, mechanical property, and swelling behavior of the hydrogel were studied. The hydrogel blend exhibited improved mechanical property and good swelling in water. The blend hydrogels also displayed typical pH-sensitive swelling behavior. A preliminary biodegradation study confirmed that the hydrogel blends undergo biodegradation by enzymatic degradation.

Preparation and Characterization of Triamcinolone Acetonide-loaded Poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHx) Microspheres

Bayram, C., Denkbas, E. B., Kilicay, E., Hazer, B., Cakmak, H. B., Noda, I. — 2008-06-03

Triamcinolone acetonide loaded in poly(3-hydroxybutyrate-co-3 hydroxyhexanoate) (PHBHx) microspheres were prepared to treat cystoid macular oedema (CMO) and acute posterior segment inflammation associated with uveitis. The PHBHx microspheres were prepared by solvent evaporation technique using methylene chloride as the solvent and aqueous poly(vinyl alcohol) emulsifier as the dispersion medium. The PHBHx microspheres obtained were well formed with narrow size distribution; the average size prepared ranged from 40—200 µm depending on the formulation used. The stirring rate of the dispersion medium, emulsifier concentration, and polymer/solvent ratio parameters were varied to determine their effect on the size and size distribution of the PHBHx microspheres. Increasing the stirring rate and emulsifier concentration decreased the size and the size distribution of the microspheres, while increasing the polymer/solvent ratio caused the opposite effect. The polymer/drug ratio was the most effective parameter for controlling drug loading and release properties. More than 90% of the loaded drug was released within the first 24 h; after that, the release rate was slower for all formulations.

Recombinant Human Bone Morphogenetic Protein-2 as an Osteoinductive Biomaterial and a Biodegradable Carrier in a Rabbit Ulnar Defect Model

2008-06-03

We investigated early local changes induced by recombinant human bone morphogenetic protein (rhBMP)-2 and a novel carrier, poly[L-lactide-co-glycolide] copolymer-coated gelatin sponge (PGS). A 1.5 cm segmental bone defect was created in the diaphysis of the right ulna of male Japanese white rabbit. Defects received PGS with or without rhBMP-2 (0, 0.4, or 1 mg/cm³) and were harvested at 3, 7, 14, 21, or 28 days post implantation for histological examination. Immuno-staining for vascular endothelial growth factor (VEGF) was also performed. Spindle-shaped cells were observed in the rhBMP-2-treated groups 3 and 7 days after implantation. Bone regeneration was detected after 14 days in the rhBMP-2-treated groups and the bone area increased with time and dose. Expression of VEGF was observed in all groups at 3 days and was maintained by 14 days only in the defects treated with rhBMP-2 at a dose of 1 mg. These results indicate that rhBMP-2 exert its osteo-inductive activities via the promotion of osteogenic cell mobilization, and possibly via angiogenesis based on VEGF induction. Foreign-body reactions to the implanted PGS were similar to those observed when either poly[L-lactide-co-glycolide] copolymer or gelatin was individually implanted. These results indicate that the PGS is a useful and safe carrier for rhBMP-2.

Chitosan Beads as Templates for Layer-by-Layer Assembly and their Application in the Sustained Release of Bioactive Agents

Grech, J. M.R., Mano, J. F., Reis, R. L. — 2008-06-03

Uncoated chitosan beads and chitosan beads coated with hyaluronic acid/chitosan (HA/Ch) multilayers, were used to investigate the controlled release of gentamicin sulphate (GS). Greater encapsulation efficiency was observed for the layer—by-layer multilayer coated beads. The in vitro drug release was in a slower sustained manner compared with noncoated chitosan beads. The differences in in vitro drug release results may be explained by the barrier effect of the coating that impedes diffusion of GS and supporting complementary water uptake. These findings indicated that a slower sustained release of gentamicin can be obtained using multilayer coatings of HA/Ch on chitosan beads and that this process could be used as a drug delivery system. In addition, agglomerates of these bead could provide a porous support in tissue engineering applications.

Synthesis of Starch--Poly(Sodium Acrylate-co-Acrylamide) Superabsorbent Hydrogel with Salt and pH-Responsiveness Properties as a Drug Delivery System

Sadeghi, M., Hosseinzadeh, H. — 2008-06-03

The synthesis and swelling behavior of a superabsorbent hydrogel based on starch (St) and polyacrylonitrile (PAN) were investigated. The physical mixture of St and PAN was hydrolyzed with NaOH solution to yield St—poly(sodium acrylate-co-acrylamide) superabsorbent hydrogels. The nitrile groups of PAN were completely converted to a mixture of hydrophilic carboxamide and carboxylate groups during the basic hydrolysis followed by in situ crosslinking of the PAN chains by the starch alkoxide ions. A mechanism for hydrogel formation was proposed and the structure of the product was established using FTIR spectroscopy. The effect of reaction variables, such as, base concentration, hydrolysis time, and temperature were systematically optimized to achieve a hydrogel with swelling capacity as high as possible. The optimized swelling capacity in distilled water was found to be >500g/g. The absorbency of the hydrogels indicated that the swelling ratios decreased with ionic strength increases. The St—poly(sodium acrylate-co-acrylamide) hydrogel exhibited a pH-responsive swelling—deswelling behavior at pH's 2 and 8. This on—off switching behavior provides the hydrogel with the potential to control delivery of bioactive agents. Release profiles of ibuprofen (IBU), a poor watersoluble drug, from the hydrogels were studied under both simulated gastric and intestinal pH conditions. The release was much quicker at pH 7.4 than at pH 1.2. The swelling rates of the hydrogels with various particle sizes were investigated as well.

Light-Cured Dimethacrylate-Based Resins and Their Composites: Comparative Study of Mechanical Strength, Water Sorption, and Ion Release

O'Donnell, J.N.R., Langhorst, S.E., Fow, M.D., Skrtic, D., Antonucci, J.M. — 2008-05-14

This study explores how resin type affects selected physicochemical properties of complex methacrylate copolymers and their amorphous calcium phosphate (ACP)-filled and glass-filled composites. Two series of photo-polymerizable resin matrices are formulated employing 2,2-bis[p-(2'hydroxy-3'-methacryloxypropoxy)phenyl]propane (Bis-GMA) or an ethoxylated bisphenol A dimethacrylate (EBPADMA) as the base monomer, unfilled copolymers and composites filled with a mass fraction with 40, 35, and 30%, respectively, of ACP or the un-silanized glass were assessed for biaxial flexure strength (BFS), water sorption (WS), and mineral ion release upon immersion in HEPES-buffered saline solution for up to six months. Substituting EBPADMA for Bis-GMA significantly reduced the WS while only marginally affected the BFS of both dry and wet copolymers. Independent of the filler level, both dry and wet ACP composites formulated with either BTHM or ETHM resins were mechanically weaker than the corresponding copolymers. The BFS of ACP composite specimens after 1 month in saline did not further decrease with further aqueous exposure. The BFS of glass-filled composites decreased with the increased level of the glass filler and the time of aqueous exposure. After 6 months of immersion, the BFS of glass-filled BTHM and ETHM composites, respectively, remained 58 and 41% higher than that of the corresponding ACP composites. Ion release data indicated that a minimum mass fraction of 35% ACP was required to attain the desired solution supersaturation with respect to hydroxyapatite for both the BTHM and ETHM derived composites.

Dynamic Co-Seeding of Osteoblast and Endothelial Cells on 3D Polycaprolactone Scaffolds for Enhanced Bone Tissue Engineering

2008-05-14

Tissue engineered scaffolds must have an organized and repeatable microstructure which enables cells to assemble in an ordered matrix that allows adequate nutriental perfusion. In this work, to evaluate the reciprocal cell interactions of endothelial and osteoblast-like cells, human osteoblast-like cells (MG63) and Human Umbilical Vein Endothelial Cells (HUVEC) were co-seeded onto 3D geometrically controlled porous poly(-caprolactone) (PCL) and cultured by means of a rotary cell culture system (RCCS-4DQ). In our dynamic co-culture system, the lack of significant enhancement of osteoblast ALP activity and ECM production indicated that the microgravity conditions of the rotary system affected the cells by favoring their proliferation and cellular cross-talk. These results emphasize how osteoblasts increase endothelial cell proliferate and endothelial cells amplify the growth of osteoblasts but decrease their differentiation. This dynamic seeding of osteoblasts and endothelial cells onto a 3D polymeric scaffold may represent a unique approach for studying the mechanisms of interaction of endothelial and osteoblast cells as well as achieve a functional hybrid in which angiogenesis, furnished by neo-vascular organization of endothelial cells may further support osteoblasts growth. Furthermore, this in vitro model may be useful in examining the applicability of novel material structures for tissue engineering.

In Vitro Osteogenic Differentiation of Rat Mesenchymal Stem Cells in a Microgravity Bioreactor

Koc, A., Emin, N., Elcin, A. E., Elcin, Y. M. — 2008-05-14

Mesenchymal stem cells (MSCs) are multipotent progenitor cells with the ability to differentiate into osteoblasts, chondroblasts, myocytes, and adipocytes. They have potential for bone tissue engineering by the utilization of in vitro expanded cells with osteogenic capacity and their delivery to the appropriate sites via biomaterial scaffolds. The objective was to evaluate the potential of rat bone marrow MSCs to form 3D bone-like tissue by the use of mineralized poly(DL-lactic-co-glycolic acid) (PLGA) foam and osteoinductive medium under rotating culture conditions. PLGA foams were prepared by solvent casting and particulate leaching, then mineralized by incubating in simulated body fluid. MSCs isolated from the bone marrow of young Wistar rats were expanded and seeded on the mineralized scaffolds. The cell-polymer constructs were then cultured in a slow turning lateral vessel-type rotating bioreactor for 4 weeks under the effect of osteogenic inducers, β-glycerophosphate, ascorbic acid and dexamethasone. Mineralization was evaluated using FT-IR and increases in dry mass; morphology changes of the mineralized foams and cell adhesion was characterized by SEM; cell viability was monitored by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide). Osteogenic differentiation was determined by using immunohistochemistry (anti-osteopontin). Results indicate the feasibility of bone tissue engineering with MSCs and mineralized PLGA scaffolds supporting cell adhesion, viability and osteogenic differentiation properties of cells in hybrid structures under appropriate bioreactor conditions.

Synthesis, Characterization, and Antibacterial Effects of Trimethylated and Triethylated 6-NH2-6-Deoxy Chitosan

2008-05-14

Chitosan, a biodegradable and biocompatible polymer, has attracted great attention in the pharmaceutical and biomedical fields especially due to its properties to reversibly open the tight junctions of the epithelial tissues and to allow for paracellular transport of hydrophilic macromolecules. However, chitosan exhibits low solubility at pH values above 6 that may prevent its enhancing effects at the sites of intestinal absorption. Hence, a number of alkylated chitosan salts have been synthesized and characterized. These derivatives have been shown to have good solubility at neutral pH and act as effective permeation enhancers. In this study, two new derivatives of chitosan, C2—C6 trimethyl 6-amino-6-deoxy chitosan and C2—C6 triethyl 6-amino-6-deoxy chitosan were synthesized and characterized using ¹H-NMR and FTIR spectra. Moreover, the zeta potential and the antibacterial properties of these polymers were compared to chitosan, trimethyl chitosan (TMC) and triethyl chitosan (TEC). Our results suggest that both C2—C6 trimethyl and triethyl 6-amino-6-deoxy chitosan, as highly water soluble polymers, have higher positive surface charge than chitosan, TMC, and TEC. Moreover, the new synthesized polymers show higher antibacterial activity against Gram-positive Staphylococcus aureus bacteria. Consequently, these polymers with substitution degrees of 50—60% may be good candidates for the enhancement of peptides in mucosal drug delivery.

Synthesis, Characterization and Preliminary Investigation of Blood Compatibility of Novel Epoxy-modified Polyurethane Networks

Yeganeh, H., Orang, F., Solouk, A., Rafienia, M. — 2008-05-14

To prepare elastomers with acceptable physical properties and good blood compatibility, polyurethane networks were synthesized via crosslinking reaction of epoxy-terminated polyurethane prepolymers (EUPs) and hexamethylene diamine. EUPs were prepared by reacting glycidol and NCO-terminated polyurethanes. All new materials were characterized by conventional spectroscopic methods and properties were evaluated and correlated to their structure. Cytotoxcicity evaluation for the films of samples based on mouse fibroblasts (L929) revealed that these elastomers posed no threat to these cells. In vitro platelet-rich plasma contact test showed reduced number of adhered platelets on the surface of the films, particularly for those with maximum crystallinity and microphase structures and high hydrophilicity. The results obtained implied the potential for the utilization of these elastomers in biomedical applications.

Rapid Prototyping of Polyurethane for the Creation of Vascular Systems

Wei Xu, , Xiao Wang, , Yongnian Yan, , Renji Zhang, — 2008-02-04

A precise control over the internal architecture was essential for manufacture of complex organs. To create vascular systems that mimic human livers, we designed and fabricated complex 3D objects with an intrinsic network of interconnected channels. A new elastomeric polyurethane, mainly based on polycaprolactone and poly(ethylene glycol) with excellent biocompatibility and tunable biodegradation properties, was used to fabricate these vascular systems using a low temperature deposition system based on the layer-by-layer manufacturing principle. A specific model was selected via computer aided design (CAD), solid free form fabrication processes are conducted under computer direction. Two example object patterns were produced by precision controlled dispensing of a biodegradable polyurethane into 3D multi-micro-tunnels with multi-micro-pores at a low temperature (-28°C). The design and fabrication strategies used to create physical objects directly from CAD models represent a promising route for the establishment of complex organ vascular systems.

Preparation and in vitro Evaluation of Linear and Star-branched PLGA Nanoparticles for Insulin Delivery

2008-02-04

Biodegradable nanoparticles, as drug delivery paradigms, have been extensively used for delivery of a wide range of small molecules as well as macromolecules, such as peptides, proteins, and genes. The morphological modification may improve the physicochemical characteristics of the biodegradable polymers. In the current investigation, the synthesis and characterization of linear, poly(D,L-lactide-co-glycolide) (PLGA)-poly(ethylene glycol) (PEG-PLGA), star-branched β-cyclodextrin-PLGA (β-CD-PLGA), and glucose-PLGA (Glu-PLGA) copolymers containing insulin as a model peptide drug have been reported. Linear and star-branched copolymers of PLGA were synthesized by bulk melt polymerization of the lactones (lactide and glycolide) in the presence of PEG, glucose, or β-CD using Sn-octoate as catalyst. Nanoparticles were prepared by a modified (w₁/o/w₂) double emulsion method. Bovine insulin was successfully encapsulated into the linear and star-branched PLGA nanoparticles with retention of insulin stability and the nanoparticles preparation process was optimized to reduce the burst effect and provide in vitro sustained release. The average particle size of samples was 120—355 nm. The cumulative amount of 65—84% insulin was released from the samples after 24 days. The yield of encapsulation of insulin was superior to 95%. Based on these findings, it is suggested that the novel PLGA nanoparticles can be used as a carrier for prolonged delivery of protein—peptide drugs.

A Novel Salted-out and Subsequently Crosslinked Poly(Lactic-co-Glycolic Acid) Polymeric Scaffold Applied to Monolithic Drug Delivery

Sibambo, S. R., Pillay, V., Choonara, Y. E., Penny, C. — 2008-02-04

This study involved a statistical approach to develop a mechanistic understanding of the salting-out of poly(lactic-co-glycolic acid) (PLGA) and to evaluate the capacity to modulate the physicochemical and physicomechanical properties of PLGA by incorporating electrolytes that produce stochastic fluctuations. The correlation between the three types of salts used and the extent of PLGA chain transitions were established by structural-thermal analysis. Drug-loaded monolithic matrices are prepared by direct compressing salted-out PLGA and a model drug (melatonin). PLGA scaffolds possess fiber diameters and volumes ranging between 0.1—15 µm and 0.0075—14,000 µm³ , respectively. Texture profile analysis reveal a significant increase in the energy absorbed and matrix resilience with increased NaCl₂ and AlCl₃ concentrations. In vitro drug release studies were performed in phosphate buffered saline (pH 7.4; 37°C); the release media was sampled at pre-determined intervals and analyzed by UV spectroscopy. Ideal zero-order drug release profiles were observed with 20% melatonin over a 30-day period. Monolithic matrices prepared by crosslinking melatonin with PLGA reveal a superior capability to control drug release. The salting-out and subsequent crosslinking of PLGA significantly modified the physicochemical and physicomechanical properties of native PLGA and demonstrated the ability to achieve controlled drug release.

Synthesis of an Amphiphilic Polysaccharide Derivative and Its Micellization for Drug Release

Lu, H.-W., Zhang, L.-M., Liu, J.-Y., Chen, R.-F. — 2008-02-04

A new route for the synthesis of novel amphiphilic polysaccharides was developed, in which a synthetic biodegradable poly(-caprolactone) was capped with a phenylalanine group (PCL-phenylalanine). The ring-opening polymerization of -caprolactone (-CL) was carried out in the absence of a metal catalyst with L-phenylalanine as the initiator; this was followed by a coupling reaction with biodegradable dextran in the presence of carbonyldimidazole. The FTIR and ¹H NMR analyses confirm the coupling reaction. Fluorescence, transmission electron microscopy (TEM), and dynamic light scattering (DLS) confirm that in aqueous solution the amphiphilic polysaccharides self-assemble into the nanoscale spherical micelles with good stability. The in vitro drug release behavior of the nonsteroidal indomethacin drug exhibits sustained drug release profile as described by the Higuchi model without a burst effect.

A Microspheric System: Hemicellulose-based Hydrogels

Edlund, U., Albertsson, A.-C. — 2008-02-04

Hydrogel microspheres were prepared from the major softwood hemicellulose polysaccharide acetylated galactoglucomannan. The dry and swollen morphology was assessed by scanning electron microscopy. The microspheres were loaded with either a small hydrophilic substance (caffeine) or a macromolecular model protein (bovine serum albumin) and afforded diffusion controlled release in vitro. Statistical multivariate analysis was used to systematically determine the influence and significance of the hydrogel composition, the crosslinking density, and the dimensions of the incorporated substance on the microsphere size and release rate.

Effect of Chitosans and Other Excipients on the Permeation of Ketotifen, FITC-Dextran, and Rhodamine 123 through Caco-2 Cells

Bejugam, N.K., Sou, M., Uddin, A.N., Gayakwad, S.G., D'Souza, M.J. — 2008-02-04

The determination of drug permeability is an important part of formulation, development, and studying the effect of excipients on drug delivery processes. Ketotifen, FITC-labeled dextran, and Rhodamine 123 permeation was evaluated across Caco-2 cells grown on permeable inserts in the presence of chitosan, N,O-carboxymethyl chitosan (NOCC), Carbopol 934P, Polysorbate 80, and Disodium edetate. Samples with chitosan decrease in transepithelial electrical resistance in a concentration dependent manner not seen with the other excipients used. This corresponds with significant improvement of paracellular permeation of FITC-dextran and Rhodamine 123 compared to the control (p<0.005) but Ketotifen permeation with chitosan does not show statistically significant improvement as compared to the control. Although Rhodamine 123 is a known p-glycoprotein substrate, this data would indicate that the p-glycoprotein transport system is not the rate limiting factor in Rhodamine 123 permeation. Ketotifen permeation is improved slightly in the presence of NOCC, Polysorbate 80, and Disodium edetate. These excipients have been associated with improved transcellular permeation. Carbopol 934P does not improve any of the drug models' permeation. These results clearly show the effectiveness of using Caco-2 cells for screening formulations and excipients for drug development.