Matrix-based delivery

Selective Genetics (San Diego, CA) Matrix-based delivery of DNA for various applications Preclinical... 

PLL and its derivatives have not been as extensively used in vivo as other cationic polymers to deliver therapeutically relevant genes however, they have found some success in systemic delivery to the liver [141] and matrix-based delivery to enhance angiogenesis [120]. Tables 7.3-5,7.3-6 (systemic), and 7.3-7 (matrix) summarize the in vivo studies involving nonviral vectors and their therapeutic outcome. 

Matrix-based delivery has been investigated mostly for regenerative medicine applications. Regenerative medicine aims to regenerate tissue by implanting biocompatible and biodegradable scaffolds at sites of injury or disease. The implanted scaffold must provide the mechanical support for the growing tissue and the bio-... 

A unique method of formulating delivery systems based on starch/ PLA systems was studied (138). In that approach, the goal was to provide a better matrix for delivery of high molecular weight hydrophilic molecules. A hydrophilic material, starch, was combined through graft polymerization to PLA. The carbolactic polymers were then used to entrap bovine serum albumin in microspheres. 

R. U. Agu, M. Jorissen, T. Willems, P. Augustijns, R. Kinget, and N. Verbeke. In-vitro nasal drug delivery studies Comparison of derivatised, fibrillar and polymerised collagen matrix-based human nasal primary culture systems for nasal drug delivery studies. J Pharm Pharmacol 53 1447-1456 (2001). 

Fig. 2.3 Reservoir- (top) and matrix-based (bottom) drug delivery systems. The matrix system degrades during drug delivery, releasing the drug and matrix through either matrix erosion or degradation.

In polymeric membrane and matrix-based micropumps, the membrane or the matrix makes the essential component of the delivery device that controls the rate of release. In matrix controlled delivery, the rate of the hydrolytic breakdown of the matrix is the governing process. In polymeric membrane-controlled release, the rate of hydration of the membrane and the subsequent diffusion of drug are the rate-controlling steps. 

Varma MVS, Kaushal AM, Garg A, Garg S. Factor affecting mechanism and kinetics of drug release from matrix-based oral controlled drug delivery systems. Am J Drug Deliv 2004 2(1 ) 43-67. 

Until recently, hot-melt extrusion had not received much attention in the pharmaceutical literature. Pellets comprising cellulose acetate phthalate were prepared using a rudimentary ram extruder in 1969 and studied for dissolution rates in relation to pellet geometry. More recently, production of matrices based on polyethylene and polycaprolactone were investigated using extruders of laboratory scale. Mank et al. reported in 1989 and 1990 on the extrusion of a number of thermoplastic polymers to produce sustained release pellets.A melt-extrusion process for manufacturing matrix drug delivery systems was reported by Sprockel and coworkers.As one can see, a review of the pharmaceutical scientific literature does not elucidate many applications for hot-melt extrusion in this field. 

Figure 7.3-2. Matrix-based DNA delivery can be divided into encapsulation and release approaches, where the nucleic acid is encapsulated for later release, and matrix-tethered delivery, where nucleic acid polyplexes or lipoplexes are immobilized directly to a matrix that also supports cell adhesion. These approaches are typically used for applications in tissue engineering where the delivery of nucleic acids is used to augment tissue formation.

In general, acellular products fabricated from human tissue that are not HCT/Ps and all acellular products derived from animal tissue fall under the Class II or Class III designation. These products for which there is a predicate device are designated as Class II and are cleared via the 510K pathway. Those products for which there is not an applicable predicate device are Class III devices and require premarket approval. A notable example is InFuse, an approved Class III device that contains a bovine collagen-based delivery matrix for rhBMP-2 (Burkus et al., 2002). 

Dmg loading in micro- and nanoparticulate systems is generally carried out by one of two methods, i.e. during the preparation of particles (incorporation) or after their formation (incubation). The dmg delivery properties are also essentially dependent on the chemical and textural properties of the matrices, the porosity, wettability, erosion and the surface area. The matrix equally has an impact on the discharge profile for the bioavailability of the entrapped dmg. Nanoparticle-based delivery systems have the potential power to improve dmg stability, increase the duration of the therapeutic effect and permit enteral or parenteral administration, which may prevent or minimize dmg degradation and metabolism as well as cellular efflux [70, 71]. Protein nanoparticles can conveyance medications transversely across the blood-brain barrier that are not usually passed across after injection. A number of authors have demonstrated a considerable tendency for an accumulation of protein nanoparticles in certain tumours. The binding of a variety of cytotoxic dmgs, such as 5-fluorouracil,... 

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