Drug delivery macromolecules

Mahmud A, Xiong X-B, Lavasanifar A (2006) Novel self-associating poly(ethylene oxide)-block-poly(E-caprolactone) block copolymers with functional side groups on the polyester block for drug delivery. Macromolecules 39 9414-9428... 

Sezaki, FI. 1989. Biopharmaceutical aspects of a chemical approach to drug delivery macromolecule-drug conjugatesYakugaku Zassrti09 611-621. 

Figure 1 Applications of bioactive polymers, (a) Imaging Polymers can incorporate multiple copies of a dye, radiotracer, or other reporter, which can lead to signal enhancement in imaging, (b) Tumor targeting and drug delivery Macromolecules can preferentially accumulate in tumor tissue by enhanced permeation and retention, (c) Inhibition Polymers can function as potent inhibitors of biological processes, (d) Activation of cell signaling Polymers can act to cluster cell-surface receptors thereby activating cell signaling.

Ethylene vinyl acetate has also found major applications in drug delivery. These copolymers used in drug release normally contain 30-50 wt% of vinyl acetate. They have been commercialized by the Alza Corporation for the delivery of pilocarpine over a one-week period (Ocusert) and the delivery of progesterone for over one year in the form of an intrauterine device (Progestasert). Ethylene vinyl acetate has also been evaluated for the release of macromolecules such as proteins. The release of proteins form these polymers is by a porous diffusion and the pore structure can be used to control the rate of release (3). Similar nonbiodegradable polymers such as the polyurethanes, polyethylenes, polytetrafluoroethylene and poly(methyl methacrylate) have also been used to deliver a variety of different pharmaceutical agents usually as implants or removal devices. 

Another very important site for drug delivery is the central nervous system (CNS). The blood-brain barrier presents a formidable barrier to the effective delivery of most agents to the brain. Interesting work is now advancing in such areas as direct convective delivery of macromolecules (and presumably in the future macromolecular drug carriers) to the spinal cord [238] and even to peripheral nerves [239]. For the interested reader, the delivery of therapeutic molecules into the CNS has also been recently comprehensively reviewed... 

J. Kopecek and R. Duncan, Poly(/V-(2-hydro-xypropyl)methacrylamide) macromolecules as drug carrier systems, in Polymers in Controlled Drug Delivery (L. Ilium and S. S. Davis, eds.), Wright, Bristol, 1987, p. 152. 

The copolymer-based systems possessing the core-shell structure in solutions are known and studied rather well (see, e.g., [14-16]). These copolymers in aqueous media tend to form polymeric micelles, which are often considered as promising drug delivery nano-vehicles [ 17,18], i.e., these macromolecular systems are not only of scientific, but also of considerable applied significance. Among such systems there are interesting examples, whose properties are very similar to the properties that should be inherent in the protein-like copolymers. All of these macromolecules possess the primary structure of... 

Patton, J. 1996. Mechanisms of macromolecule absorption by the lungs. Advanced Drug Delivery Reviews 19, 3-36. 

H. Sezaki, M. Hashida, Macromolecules as Drug Delivery Systems , in Directed Drug Delivery - A Multidisciplinary Approach , Eds. R. T. Borchardt, A. J. Repta, V. J Stella, Humana Press, Chfton, N. J., 1985, p. 189-208. 

The failure in increasing residence time of mucoadhesive systems in the human intestinal tract has led scientists to the evaluation of multifunctional mucoadhesive polymers. Research in the area of mucoadhesive drug delivery systems has shed light on other properties of some of the mucoadhesive polymers. One important class of mucoadhesive polymers, poly(acrylic acid) derivatives, has been identified as potent inhibitors of proteolytic enzymes [72-74]. The interaction between various types of mucoadhesive polymers and epithelial cells has a direct influence on the permeability of mucosal epithelia by means of changing the gating properties of the tight jrmctions. More than being only adhesives, some mucoadhesive polymers can therefore be considered as a novel class of multifunctional macromolecules with a number of desirable properties for their use as delivery adjuvants [72,75]. 

There are several consequences of these anomalies in pressnre gradients for the delivery and distribution of drugs and macromolecules within the tnmonr interstitinm. First, high interstitial pressures mean that the central regions of the tnmonr, already poorly perfused, demonstrate low or non-existent convective flow into the interstitinm. Fnrthermore, interstitial convective flow will tend to radiate outward from the centre, towards the periphery and regions of lower interstitial pressure. Therefore, only small amonnts of drngs or macromolecules will reach cells in the centre of the tumour. At the tumour periphery, where convective transfer across the blood vessel wall might take place, further movement towards the centre of the tumour will be impeded by bulk flow in the opposite direction. 

In summary, in solid tumours the laws of hydrodynamics and transport of solutes mitigate against the successful delivery of drugs and macromolecules to tumour cells. 

RME shows particular promise in the recovery of proteins/enzymes [12-14]. In the past two decades, the potential of RME in the separation of biological macromolecules has been demonstrated [15-20]. RMs have also been used as media for hosting enzymatic reactions [21-23]. Martinek et al. [24] were the first to demonstrate the catalytic activity of a-chymotrypsin in RMs of bis (2-ethyl-hexyl) sodium sulfosuccinate (Aerosol-OT or AOT) in octane. Since then, many enzymes have been solubilized and studied for their activity in RMs. Other important applications of RME include tertiary oil recovery [25], extraction of metals from raw ores [26], and in drug delivery [27]. Application of RMs/mi-croemulsions/surfactant emulsions were recognized as a simple and highly effective method for enzyme immobilization for carrying out several enzymatic transformations [28-31]. Recently, Scheper and coworkers have provided a detailed account on the emulsion immobiUzed enzymes in an exhaustive review [32]. 

L.R.Brown, C.L.Wei and R.Langer,/ vivo and in v/ft-o release of macromolecules from polymeric drug delivery... 

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