Hydrophilicity drug carriers

Recently, many studies have focused on self-assembled biodegradable nanoparticles for biomedical and pharmaceutical applications. Nanoparticles fabricated by the self-assembly of amphiphilic block copolymers or hydrophobically modified polymers have been explored as drug carrier systems. In general, these amphiphilic copolymers consisting of hydrophilic and hydrophobic segments are capable of forming polymeric structures in aqueous solutions via hydrophobic interactions. These self-assembled nanoparticles are composed of an inner core of hydrophobic moieties and an outer shell of hydrophilic groups [35, 36]. 

An important group of surface-active nonionic synthetic polymers (nonionic emulsifiers) are ethylene oxide (block) (co)polymers. They have been widely researched and some interesting results on their behavior in water have been obtained [33]. Amphiphilic PEO copolymers are currently of interest in such applications as polymer emulsifiers, rheology modifiers, drug carriers, polymer blend compatibilizers, and phase transfer catalysts. Examples are block copolymers of EO and styrene, graft or block copolymers with PEO branches anchored to a hydrophilic backbone, and star-shaped macromolecules with PEO arms attached to a hydrophobic core. One of the most interesting findings is that some block micelle systems in fact exists in two populations, i.e., a bimodal size distribution. 

In terms of biodistribution, Zhang et al. (1997) were not able to demonstrate any difference between the biodistribution of paclitaxel loaded into MePEGQLLA micelles versus paclitaxel solubilized in Cremophor EL (a conventional surfactant). These two formulations also showed similar in vitro distribution between the lipoprotein and lipoprotein-deLcient fraction of plasma (Ramaswamy et al., 1997). As for other drug carriers, plasma half-life and uptake of polymeric micelles by the MPS depend on the molecular weight (Kwon et al., 1994) and density of the hydrophilic shell (Hagan et al., 1996). 

Small size (10-100 nm) is one ofthe most interesting features of polymeric micelles. Besides allowing the extravasation of the carriers, it permits the sterilization of the preparation to be done simply by Lltration and minimizes the risks of embolism in capillaries, contrary to larger drug carriers (Kwon and Okano, 1996). Micellar size seldom exceeds 100 nm, but depends on several factors including copolymer molecular weight, relative proportion of hydrophilic and hydrophobic chains, and aggregation number (Yokoyama etal., 1990 Trubetskoy and Torchilin, 1996 Shin etal., 1998). 

FIGURE 22.6 Permeability and permselectivity of vaginal and buccal epithelia in the rabbit, (a) Flux of 6-carboxyfluoroscein, a hydrophilic molecule, by in vitro perfusion studies steady-state flux ( xg/cm2/h x 106), (b) resistance (fl cm2 x 10 2), (c) thickness (p,m x 10-2), and (d) ratio of potassium transport number to chloride transport number, which is calculated from electrical measurements, used as indicative of the epithelium selectivity for positively charged molecules. (Modified from Sayani, A.P. and Chien, Y.W., Crit. Rev. Ther. Drug Carrier Syst. 13, 85, 1996.)... 

Polyelectrolyte complexes of retinoic acid have been well investigated, they are pharmaceutically active surfactants. In the following, we will therefore discuss the physicochemical properties of drug carriers formed by synthetic polyamino acids, polyethyleneimine, double hydrophilic block copolymers and retinoic acid. 

Highly disperse silica is widely used in pharmaceutical formulations as a filler, adsorbent, thickener etc.5 Their high hydrophilicity and the absence of emulsifying ability restrict their application. In contrast to hydroxylated silica, partially or fully hydrophobized silica may exhibit improved properties as a drug carrier. The main goal of this work is to study hydrophobized silica nanocomposites with immobilized vitamins C and E. Investigations of adsorption-desorption processes which involve silica nanoparticles and the antioxidants are described. Factors affecting the antioxidant stability have also been carefully considered. 

Micellar systems based on amphipathic block-copolymers have gained most attention as intravenously administered drug carrier systems over the years. These block-copolymers are composed of a hydrophilic PEG block and a hydrophobic block based on doxorubicin conjugated poly(aspartic acid) or poly(/i-bcnzyl L-aspartate). 

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