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Controlled Delivery (controlled + delivery)
Selected AbstractsControlled Delivery Achieved with Bi-Layer Matrix Devices Produced by Co-Injection MouldingMACROMOLECULAR BIOSCIENCE, Issue 8 2004Cláudia M. Vaz Abstract Summary: The aim of this study was to design new soy protein-based bi-layered co-injection moulded matrix systems aimed to achieve controlled drug delivery. The devices consisted of a drug-free outer layer (skin) and a drug-containing core. The systems overcame the inherent disadvantage of non-linear release associated with diffusion-controlled single-layer matrix devices by providing additional releasing area with time to compensate for the decreasing release rate. As expected, the bi-layer devices presented a significant decrease in drug release rate when compared with a correspondent single layer matrix system. The skin thickness and the degree of crosslinking of the core appeared to be very important tools to tailor the release patterns. Furthermore, due to the amphoteric nature of the soy protein, the developed devices evidenced a pH-dependent behaviour. The mechanisms of drug release were also elucidated at two different pH values: i) pH 5.0, near the isoelectric point of soy (low matrix solubility); and ii) pH 7.4, physiological pH (high matrix solubility). Consequently, changing the release medium from pH 5.0 to pH 7.4 after two hours, led to an abrupt increase in drug release and the devices presented a typical controlled drug delivery profile: slow release/fast release. These evidences may provide for the development of individual systems with different release onsets that in combination may exhibit drug releases at predetermined times in a pre-programmed way. Another possibility is the production of three-layer devices presenting bimodal release profiles (fast release/slow release/fast release) by similar technologies. Scanning electron micrograph of a developed bi-layer device. [source] Controlling Affinity Binding with Peptide-Functionalized Poly(ethylene glycol) HydrogelsADVANCED FUNCTIONAL MATERIALS, Issue 14 2009Chien-Chi Lin Abstract Poly(ethylene glycol) (PEG) hydrogels functionalized with peptide moieties have been widely used in regenerative medicine applications. While many studies have suggested the importance of affinity binding within PEG hydrogels, the relationships between the structures of the peptide motifs and their binding to protein therapeutics remain largely unexplored, especially in the recently developed thiol-acrylate photopolymerization systems. Herein, Förster resonance energy transfer (FRET) and thiol-acrylate photopolymerizations are employed to investigate how the architectures of affinity peptides in crosslinked hydrogels affect their binding to diffusible proteins. The binding between diffusible streptavidin and biotinylated peptide immobilized to PEG hydrogel network was used as a model system to reveal the interplay between affinity binding and peptide sequences/architectures. In addition, peptides with different structures are designed to enhance affinity binding within PEG hydrogels and to provide tunable affinity-based controlled delivery of basic fibroblast growth factor (bFGF). This study demonstrates the importance of affinity binding in controlling the availability of hydrogel-encapsulated proteins and provides strategies for enhancing affinity binding of protein therapeutics to bound peptide moieties in thiol-acrylate photopolymerized PEG hydrogels. The results presented herein should be useful to the design and fabrication of hydrogels that retain and exhibit sustained release of growth factors for promoting tissue regeneration. [source] Antimicrobial Gallium-Doped Phosphate-Based Glasses,ADVANCED FUNCTIONAL MATERIALS, Issue 5 2008Sabeel P. Valappil Abstract Novel quaternary gallium-doped phosphate-based glasses (1, 3, and 5 mol % Ga2O3) were synthesized using a conventional melt quenching technique. The bactericidal activities of the glasses were tested against both Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Clostridium difficile) bacteria. Results of the solubility and ion release studies showed that these glass systems are unique for controlled delivery of Ga3+. 71Ga NMR measurements showed that the gallium is mostly octahedrally coordinated by oxygen atoms, whilst FTIR spectroscopy provided evidence for the presence of a small proportion of tetrahedral gallium in the samples with the highest gallium content. FTIR and Raman spectra also afford an insight into the correlation between the structure and the observed dissolution behavior via an understanding of the atomic-scale network bonding characteristics. The results confirmed that the net bactericidal effect was due to Ga3+, and a concentration as low as 1 mol % Ga2O3 was sufficient to mount a potent antibacterial effect. The dearth of new antibiotics in development makes Ga3+ a potentially promising new therapeutic agent for pathogenic bacteria including MRSA and C. difficile. [source] The optimal mode of delivery for the haemophilia carrier expecting an affected infant is caesarean deliveryHAEMOPHILIA, Issue 3 2010A. H. JAMES Summary., While a majority of affected infants of haemophilia carriers who deliver vaginally do not suffer a head bleed, the outcome of labour cannot be predicted. A planned vaginal delivery puts a woman at risk of an abnormal labour and operative vaginal delivery, both of which predispose to intracranial haemorrhage. Furthermore, vaginal delivery does not eliminate the risk to the haemophilia carrier herself. Overall, maternal morbidity and mortality from planned vaginal delivery are not significantly different from those from planned caesarean delivery. Caesarean delivery is recommended or elected now in conditions other than haemophilia carriage, where the potential benefits are not nearly as great. Additionally, vaginal delivery of the haemophilia carrier poses medical/legal risks if the infant is born with cephalohaematoma or intracranial haemorrhage. Caesarean delivery allows for a planned, controlled delivery. Caesarean delivery reduces the risk of intracranial haemorrhage by an estimated 85% and the risk can be nearly eliminated by performing elective caesarean delivery before labour. Therefore, after a discussion of the maternal and foetal risks with planned vaginal delivery versus planned caesarean delivery, haemophilia carriers should be offered the option of an elective caesarean delivery. [source] Enhanced flexor tendon healing through controlled delivery of PDGF-BBJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 9 2009Stavros Thomopoulos Abstract A fibrin/heparin-based delivery system was used to provide controlled delivery of platelet derived growth factor BB (PDGF-BB) in an animal model of intrasynovial flexor tendon repair. We hypothesized that PDGF-BB, administered in this manner, would stimulate cell proliferation and matrix remodeling, leading to improvements in the sutured tendon's functional and structural properties. Fifty-six flexor digitorum profundus tendons were injured and repaired in 28 dogs. Three groups were compared: (1) controlled delivery of PDGF-BB using a fibrin/heparin-based delivery system; (2) delivery system carrier control; and (3) repair- only control. The operated forelimbs were treated with controlled passive motion rehabilitation. The animals were euthanized at 7, 14, and 42 days, at which time the tendons were assessed using histologic (hyaluronic acid content, cellularity, and inflammation), biochemical (total DNA and reducible collagen crosslink levels), and biomechanical (gliding and tensile properties) assays. We found that cell activity (as determined by total DNA, collagen crosslink analyses, and hyaluronic acid content) was accelerated due to PDGF-BB at 14 days. Proximal interphalangeal joint rotation and tendon excursion (i.e., tendon gliding properties) were significantly higher for the PDGF-BB-treated tendons compared to the repair-alone tendons at 42 days. Improvements in tensile properties were not achieved, possibly due to suboptimal release kinetics or other factors. In conclusion, PDGF-BB treatment consistently improved the functional but not the structural properties of sutured intrasynovial tendons through 42 days following repair. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [source] Time-Resolved Small-Angle Neutron Scattering as a Tool for Studying Controlled Release from Liposomes using Polymer-Enzyme ConjugatesMACROMOLECULAR RAPID COMMUNICATIONS, Issue 19 2010Elaine L. Ferguson Abstract The action of phospholipase A2 (PLA2) on 1,2-dipalmitoyl- sn -glycero-3-phosphocholine (DPPC) liposomes (vesicles) , an integral component in the polymer enzyme liposome therapy (PELT) mechanism (R. Duncan et al., J. Controlled Release2001, 74, 135) for the controlled delivery of poorly soluble therapeutic molecules within liposomes , may be "masked" by conjugation to the biodegradable polymer dextrin and subsequently regenerated by the endogenous enzyme , -amylase that degrades the dextrin; that is, incorporating the so-called polymer-unmasked-masked protein therapy (PUMPT) approach (R. Duncan, et al. Biomacromolecules2008, 9, 1146). Small-angle neutron scattering (SANS) has been used to quantify the detailed structure of DPPC liposomes and any perturbation in that structure induced by the presence of PLA2 in native, "masked" (dextrin,PLA2 conjugate) and an in situ , -amylase-unmasked form. A time-dependent degradation of the vesicular structure was observed for the two active PLA2 cases, but not for the masked case. This study demonstrates that the PLA2 -induced hydrolysis of the DPPC , and the associated rupture of the liposome and the release of the enclosed material , may be controlled through masking with dextrin. Accordingly, the viability of using such a combinatorial nanomedicine approach as a general route for the controlled delivery of poorly soluble therapeutic molecules is shown. [source] Parameters Influencing the Release of Tertiary Alcohols from the Surface of "Spherical" Dendrimers and "Linear" Stylomers by Neighbouring-Group-Assisted Hydrolysis of 2-CarbamoylbenzoatesCHEMISTRY - A EUROPEAN JOURNAL, Issue 12 2009Alain Trachsel Abstract Size is not all! Investigation of the controlled release of tertiary alcohols from the surface of dendrimers and "stylomers" as polymer model systems (see scheme) showed that the polarity of the conjugates and structural modifications in close proximity to the release unit have a stronger influence on the rates of hydrolysis than the size (generation) or shape (linear or spherical) of the macromolecules. The influence of structural and physico-chemical parameters on the release of a volatile tertiary alcohol (2-methyl-1-phenyl-2-propanol) by neighbouring-group-assisted cyclisation of 2-carbamoylbenzoates at neutral pH was investigated by comparing the covalent-bond cleavage from the surface of linear, comblike poly(propylene imine) "stylomers" and their corresponding spherical, globular dendrimers. Determination of the kinetic rate constants for the stepwise intramolecular cyclisation of the 2-carbamoylbenzoate moiety by using HPLC showed that the polarity of the conjugates, and thus their solubility in the aqueous reaction medium, has a stronger influence on the rates of hydrolysis than the size (generation) or shape (linear or spherical) of the macromolecules. Furthermore, structural modifications in close proximity to the release unit, such as the presence of functionalities with catalytic activity, have a strong impact on the release efficiency of the active molecules. An understanding of the physico-chemical parameters determining the local environment of the covalent-bond cleavage site is therefore an important prerequisite to transfer the characteristics of small molecules to larger structures such as oligomers and polymers and thus to design efficient macromolecular conjugates for the controlled delivery of bioactive compounds. L'influence des paramètres structurels et physico-chimiques sur le relargage à pH neutre d'un alcool tertiaire volatil (2-méthyl-1-phényl-2-propanol) par cyclisation de 2-carbamoylbenzoates assistée par un groupe voisin a été étudiée. Les ruptures de liaisons covalentes depuis la surface de poly(propylene imines) en forme de peigne ("stylomères") d'une part et de leurs analogues sphériques et globulaires (dendrimères) correspondants d'autre part ont été comparées. La détermination par CLHP des constantes cinétiques pour la cyclisation intramoléculaire des unités 2-carbamoylbenzoate par étapes a montré que la polarité des conjugués, et par conséquent leur solubilité dans le milieu de réaction aqueux, a une influence plus forte sur les vitesses d'hydrolyse que la taille (génération) ou la forme (linéaire ou sphérique) des macromolécules. De plus, des modifications structurelles à proximité immédiate de l'unité de relargage telles que la présence de groupes fonctionnels avec une activité catalytique ont un fort impact sur l'efficacité de relargage des molécules actives. La compréhension des paramètres physico-chimiques qui déterminent l'environnement local du site de rupture de la liaison covalente est par conséquent une condition préalable importante lors du transfert de caractéristiques de petites molécules à des structures plus grandes telles que des oligomères et des polymères, et donc à la conception de conjugués macromoléculaires efficaces pour le relargage contrôlé de composés bioactifs. [source] | ||||||||||