1. Passive Drug Targeting: The EPR Effect Passive targeting is a drug delivery approach in which drugs are delivered to the targeted site by conjugating with polymer which releases the drug outside the targeted site due to altered environmental conditions (Figure 6(a)). Tumors and many inflamed areas of body have Sorafenib research buy hyperpermeable vasculature and poor lymphatic drainage which passively provides increased retention of macromolecules Inhibitors,research,lifescience,medical into tumor and inflamed area of body [27–30]. This phenomenon is called enhanced permeability and retention (EPR) effect [27]. It constitutes one of the practical carrier-based anticancer drug delivery strategies. EPR effect is primarily

utilized for passive targeting due to accumulation of prodrug

into tumor or inflamed area. Low molecular Inhibitors,research,lifescience,medical drugs covalently coupled with high-molecular-weight carriers are inefficiently eliminated due to hampered lymphatic drainage and therefore accumulate in tumors. While EPR effect enhances the passive targeting ability due to higher accumulation rate of drug in tumor and subsequently due to accumulation, prodrug slowly releases drug molecules which provide high bioavailability and low systemic toxicity [30]. Passive accumulation of macromolecules such as PEG and other nanoparticles Inhibitors,research,lifescience,medical in solid tumors is a phenomenon which was probably overlooked for several years as a potential biological target for tumor-selective drug delivery. The existence of the EPR effect was experimentally confirmed by David et al., for Inhibitors,research,lifescience,medical macromolecular anticancer drug delivery systems [31]. Furthermore, passive targeting increases the concentration of the conjugate in the tumor environment and therefore “passively” forces the polymeric drug to enter the cells Inhibitors,research,lifescience,medical by means of the concentration gradient between the intracellular and extracellular spaces and therefore is not very efficient. The more efficient way to provide targeting is by “active

targeting” [32]. 4.2. Active Targeting Active targeting approach is based on interaction between specific biological pairs (e.g., ligand receptor, antigen antibody, enzyme substrate) (Figure 6(a)) [33]. Active targeting is achieved by attaching targeting agents that bind to specific receptors on the cell surface—to the prodrug by a variety of conjugation chemistries. Most widely used targeting moieties are peptide 3-mercaptopyruvate sulfurtransferase ligands, sugar residues, antibodies, and aptamers specific to particular receptors, selectins, antigens, and mRNAs expressed in targeted cells or organs. The targeted anticancer LHRH-PEG-CPT conjugate is an example of such targeted anticancer drug delivery system [7]. In this system, LHRH peptide is used as a targeting moiety to the corresponding receptors overexpressed in several cancer cells, PEG polymer—as a carrier and CPT—as an anticancer drug.