Chemical conjugate

At present, the most frequently used methods for PEGylation are chemical conjugation between reactive groups in the drug, such as the primary amine of lysine in protein, and end-reactive PEG derivatives, such as the A-hydroxysuccinimide-... 

Polymeric micelles are mostly small (10-100 nm) in size and dmgs can be incorporated by chemical conjugation or physical entrapment. For efficient delivery activity, they shonld maintain their integrity for a sufficient amount of time after injection into the body. Most of the experience with polymeric micelles has been obtained in the field of passive targeting of anticancer drugs to tumours [33]. Attachment of antibodies or sugars, or introduction of a polymer sensitive to variation in temperature or pH has also been stndied [32]. 

NGF chemically conjugated to 0X26 6.2 pg/ injection i.v. injection 4x every 2 weeks Rat intraocular forebrain Survival of cholin-transplant ergic neurons ... 

NGF chemically conjugated to anti primate TfR mAh AK30 i.v. injection Non-human primate Upregulation of p75 NGF-receptor in striatum... 

The B block may consist of a water-soluble polymer, for example, poly(aspartic acid) P(Asp), that is rendered hydrophobic by the chemical conjugation of a hydrophobic drug (Yokoyama et al., 1992, 1993, 1996 Nakanishi et al., 2001), or is formed through the association of two oppositely changed polyions (polyion complex micelles) (Hatada etal., 1995,1998 Kataoka etal., 1996). Drugs used to couple the B block include cyclophosphamide, doxorubicin, cisplatin, pyrene, and iodine derivative of benzoic acid (Kwon and Kataoka, 1995 Trubetskoy et al., 1997 Yu etal., 1998). 

As compared with other types of carrier systems, the polymeric micelle systems possess several beneLts (Yokoyama, 1992, 1994) including the wide applicability of polymeric micelle systems to drugs, through either chemical conjugation or physical entrapment and the small size of polymeric micelles. In the case of physical entrapment, utilizing hydrophobic interactions can be applied to many kinds of drugs (Kwon et al., 1994) because most drugs contain hydrophobic moiety(ies) in their chemical structures. 

Yokoyama et al. (1998) reported the procedures for chemical conjugation of adriamycin (ADR) into polymeric micelles that was based on a reference (Yokoyama et al., 1994) with some modiLcations The copolymer used by Yokoyama et al. (1998) was polyethylene gljBept)ly(aspartic acid) block copolymer (PEG-P(Asp)). Molecular weight of the (PEG) chain and the (P(Asp)) chain was... 

Yokoyama M., S. Fukushima, R. Uehara, K. Okamoto, K. Kataoka, Y. Sakurai, and T. Okano. 1998. Characterization of physical entrapment and chemical conjugation of adriamycin in polymeric micelles and their design foin vivo delivery to a solid tumot). Control. Rel50 79-92. 

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