Macromolecular carriers

Numerous experimental therapeutics have shown potency in vitro however, when they are tested in vivo, they often lack significant efficacy. This is often attributed to unfavorable pharmacokinetic properties and systemic toxicity, which limit the maximum tolerated dose. These limitations can be overcome by use of drug carriers. Two general types of carrier systems have been designed drug conjugation to macromolecular carriers, such as polymers and proteins and drug encapsulation in nanocarriers, such as liposomes, polymersomes and micelles. 

In cancer treatment, passive targeting of macromolecular carriers to tumors is a commonly used approach. This passive targeting is based on the enhanced permeability and retention (EPR) effect, which leads to an accumulation of the high molecular weight carrier in the tumor tissue. The EPR effect arises from the different physiology of tumor vasculature, where the vessel walls are highly porous and lack the tight junctions that are present in healthy tissue. As a result, macromolecular carriers extravasate and accumulate preferentially in tumor tissue relative to normal tissues [63, 64]. 

All the aforementioned advantages and several additional features apply to ELP-based macromolecular carriers. First, ELP-based carriers are thermally responsive. Second, ELP is a biopolymer and therefore is nontoxic and biodegradable. Third, the gene-based synthesis of ELP allows the creation of genetic fusions with functional peptides and proteins, such as targeting sequences. 

The choice of a macromolecular carrier depends on the intended clinical objectives and the nature of the therapeutic agents being used. In general, the properties of an ideal soluble carrier system include the following... 

Dextrans are also attractive as macromolecular carriers of paramagnetic chelates because of their hydrophilicity, the different available molecular weights with narrow polydispersity, and the versatility of activation methods applicable. Several DTPA- or DOTA-loaded carboxymethyl dextran (CMD) derivatives have been prepared and tested in blood pool MRI.136-139 The relaxivities reported for these compounds are, however, relatively moderate. 

Albmnin is one of the soluble macromolecular carriers available for drug targeting purposes. With a molecular weight of approximately 67 kDa, it is small in size as compared to other potential carriers. It can be derivatized with molecules that will determine its cell specificity, and with drug molecules. A maximum of about 60 molecules can be coupled to albumin through the e-NHj of the lysine residues. Table 4.1 shows the modified albmnins that have been used for targeting to SECs and KCs. 

Renal Delivery Using Macromolecular Carriers The Low Molecular Weight Protein Approach 135... 

The pharmacokinetic properties of macromolecular carrier systems for targeted drug delivery were reviewed by Takakura and Hashida [8]. 

Examples of polymeric carriers are presented in Table 1 and typical methods of covalent conjugation are shown below. Drugs may be bound to macromolecular carriers via, e.g., ester, amide, urethane, hydrazone, thioether, and disulfide... 

Targeting a drug to its site of action is useful to enhance its effectiveness and reduce toxicity. If accessible this can be achieved by direct local application, e.g. eye drops to treat ophthalmic conditions, inhalers to treat respiratory conditions, but currently strategies such as the development of targeting agents such as monoclonal antibodies or the use of the more permeable nature of tumour capillaries to allow accumulation of macromolecular carriers have also been employed. 

Iodophors are labile complexes of elemental iodine with macromolecular carriers that both increase the solubility and provide sustained release of iodine. Povidone-iodine is a water-soluble iodophor that is used as an antiseptic and is said to be free of the undesirable effects of iodine tincture. However, iodine can be absorbed from it through burned areas (17), vaginal mucosa (18), oral mucosa (19), and in children even with normal skin (20). Povidone-iodine is discussed in a separate monograph under the title Polyvidone. 

Rolland, A., I. E. O Mullane, P. Goddard, L. Brookman, and K. Pettrak. 1992. New macromolecular carriers for drugs, I. Preparation and characterization of poly(oxyethyl ra prene-boxyethylene) block copolymer aggregated. Appl. Polym. Sci44 1195-1203. 

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