International Journal of Pharmaceutics 334 (2007) 48–55 ABA and BAB type triblock copolymers of PEG and PLA: A comparative study of drug release properties and “stealth” particle characteristics Guosen He, Lwin Lwin Ma, Jie Pan, Subbu Venkatraman ∗ Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue N4.1, Singapore 639798, Singapore Received 15 July 2006; received in revised form 30 August 2006; accepted 10 October 2006 Available online 21 October 2006 Abstract We synthesized two types of triblock copolymers containing PEG and PLA as controlled release carriers of hydrophobic drugs: these are the ABA type (PLA–PEG–PLA) and the BAB type (PEG–PLA–PEG). These polymers are amphiphilic and can form nanomicelles (40–200 nm) in aqueous medium. On the surface of PLA–PEG–PLA (ABA) type nanomicelles, the PEG content was enhanced somewhat over the bulk amount; whereas in the PEG–PLA–PEG (BAB type), surface segregation was much higher. The copolymers tested can entrap 35% of paclitaxel by weight on the average. In general, the diffusion-controlled release of paclitaxel is slower for the BAB polymers; furthermore, the actual release rates are influenced by the PLLA lengths in the BAB copolymers. Surface PEG contents influence the “stealth” characteristics of the nanomicelles. Compared with PLA particles, all nanomicellar particles tested, of both BAB and ABA types, showed a four-fold reduction in monocyte cell uptake, with the BAB type copolymer exhibiting a lesser uptake. © 2006 Elsevier B.V. All rights reserved. Keywords: Block; Copolymer; Drug carriers; Paclitaxel release; Immuno-cellular uptake; Opsonization 1. Introduction Biodegradable materials have been attracting increasing interest for use in biomedical devices (Reis and Roman, 2004; Sachlos and Czernuszka, 2003; Laurencin et al., 1999; Vats et al., 2003). Although earlier applications focused on homopolymers of poly(l-lactide) (PLLA) or poly(glycolide) (PGA) and their random copolymers (PLGA), increasing attention is focused on the development of diblock copolymers such as PLA–PEG and PLGA–PEG, and their corresponding triblocks as drug carri- ers for controlled drug release (Kanjickal and Lopina, 2005; Bala et al., 2005; Pan et al., 2005). The amphiphilic character of these copolymers enables the formation of micelles in water through a self-assembly process at low concentration, with the hydrophobic PLA or PLGA serving as core reservoirs for drug and the hydrophilic PEG as the shell projecting into the aque- ous environment. The use of PEG in the copolymers is also to reduce particle uptake by the mononuclear phagocytic system, sometime also referred to as the “stealth function”, compared ∗ Corresponding author. Tel.: +65 67904259; fax: +65 67909081. E-mail address: Assubbu@ntu.edu.sg (S. Venkatraman). with the particles without PEG attachment (Gref et al., 1994, 2000). The opsonization-inhibiting property of PEG enables long circulation times of drug in vivo. In addition, proteins and plasmid DNA may also be incorporated into PEG-“coated” par- ticles, indicating the potential application of the copolymers in immuno- and gene therapies (Vila et al., 2002; Jeong et al., 1997). Besides possessing physical properties and functions simi- lar to the PLA/PLGA–PEG–PLGA/PLA (ABA type) copoly- mers, mPEG–PLA/PLGA–mPEG (BAB type, also written as PEG–PLA/PLGA–PEG) copolymers were recently reported to undergo sol–gel transition from aqueous solutions at body tem- perature (Jeong et al., 1999; Li et al., 2003). The hydrogel of PEG–PLGA–PEG once formed in the body (in mice) can retain its integrity for more than 1 month, suggesting that it is ideal for slow-release systems to treat chronic diseases such as cancer and hypertension. One of the most successful cancer drugs, paclitaxel, has shown its potency against a broad spectrum of cancers (Rowinsky et al., 1992; Rowinsky and Donehover, 1995; Lopes et al., 1993; Redhead et al., 2001). Paclitaxel is strongly hydrophobic and Taxol ® , the dosage form of paclitaxel for administration, contains 50% Cremophor ® EL to increase its 0378-5173/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.ijpharm.2006.10.020