Hydrophilicity delivery

The hydrophilic delivery system described in this review can be extended to drugs with a low water-solubility (e.g., doxorubicin). Such compounds may be incorporated in CT/TPP nanoparticles by means of dextran sulfate complex prior to entrapment [54] or by dissolving them in a polar solvent (acetone, ethanol or acetonitrile) as demonstrated for the relatively hydrophobic peptide cyclosporin A [26,81]. It is quite possible that this approach would work in a multicomponent polymer system as well. 

Associations can be of physical nature too. Chitosan blends with hydrophilic polymers including polyvinylalcohol, polyethyleneoxide and poly-vinylpyrrohdone, were investigated as candidates for oral gingival delivery systems. Chitosan blends were superior to chitosan alone in terms of comfort, ease of processing, film quality, and flexibihty [325]. 

Dendrimer micelles of this type have been formulated as drug delivery vehicles. Dendrimers with a hydrophobic interior have been used to entrap a hydrophobic drug such as indomethacin. This is retained because of the hydrophilic periphery containing ethylene glycol functional groups, and is released slowly because of the collapsed configuration of the interior, through which molecular diffusion is obstructed. 

Recently, unique vesicle-forming (spherical bUayers that offer a hydrophilic reservoir, suitable for incorporation of water-soluble molecules, as well as hydrophobic wall that protects the loaded molecules from the external solution) setf-assembUng peptide-based amphiphilic block copolymers that mimic biological membranes have attracted great interest as polymersomes or functional polymersomes due to their new and promising applications in dmg delivery and artificial cells [ 122]. However, in all the cases the block copolymers formed are chemically dispersed and are often contaminated with homopolymer. 

A unique method of formulating delivery systems based on starch/ PLA systems was studied (138). In that approach, the goal was to provide a better matrix for delivery of high molecular weight hydrophilic molecules. A hydrophilic material, starch, was combined through graft polymerization to PLA. The carbolactic polymers were then used to entrap bovine serum albumin in microspheres. 

In conclusion, delivery of liposome-encapsulated drugs in eye drops can improve the extent of uptake and the residence time compared to the free drug. In particular, lipophilic substances seem to benefit from this approach. The exact mechanism behind the improved biopharmaceutical behavior still has to be unraveled. Intra-vitreal injection of drug-containing liposomes increases the residence times of both hydrophilic and lipophilic drugs. 

Micellar nanocarriers have already been applied successfully for delivery of hydro-phobic drugs [86]. These carriers are usually the product of self-assembled block copolymers, consisting of a hydrophilic block and a hydrophobic block. Generally, an ELP with a transition temperature below body temperature is used as hydrophobic block and the hydrophilic block can be an ELP with a transition temperature above body temperature or another peptide or protein. The EPR effect also directs these types of carriers towards tumor tissue. 

In 2000, the first example of ELP diblock copolymers for reversible stimulus-responsive self-assembly of nanoparticles was reported and their potential use in controlled delivery and release was suggested [87]. Later, these type of diblock copolypeptides were also covalently crossUnked through disulfide bond formation after self-assembly into micellar nanoparticles. In addition, the encapsulation of l-anilinonaphthalene-8-sulfonic acid, a hydrophobic fluorescent dye that fluoresces in hydrophobic enviromnent, was used to investigate the capacity of the micelle for hydrophobic drugs [88]. Fujita et al. replaced the hydrophilic ELP block by a polyaspartic acid chain (D ). They created a set of block copolymers with varying... 

ELP-based triblock copolypeptides have also been used to produce stimulus-responsive micelles, and Chaikof and coworkers envisioned the possible application of these micelles as controlled drug delivery vehicles. These amphiphilic triblock copolymers were constructed from two identical hydrophobic ELP endblocks and a hydrophilic ELP midblock. Below the transition temperature, loose and monodispersed micelles were formed that reversibly contracted upon heating, leading to more compact micelles with a reduced size [90]. 

Historically, after the development of oligopeptide-based vesicles, several groups developed and characterized vesicles using polypeptide hybrid systems consisting of polypeptide and synthetic polymer blocks [17-19]. Soon thereafter, vesicles formed entirely from polypeptides, such as poly(L-lysine)-h-poly(L-leucine) and poly(L-lysine)-h-poly(L-glutamate), were developed [20, 21]. This review will focus on recent developments in the formation of vesicles composed of polypeptide hybrid or polypeptide systems, as well as the potential promise of these systems as effective dmg delivery vehicles. A specific example of a polypeptide-based vesicle is shown in Fig. 1, where the hydrophobic segment is a-helical and the hydrophilic segment is a random coil. 

Solubilization of vinylpyrrolidone, acrylic acid, and A,A -methylene-bis-acrylamide in AOT-reversed micelles allowed the synthesis in situ of a cross-linked polymer with narrow size distribution confined in the micellar domain. These particles displayed high entrapment efficiency of small hydrophilic drugs and have been considered interesting drug delivery systems [239],... 

We have also determined the delivery sites of alkylbenzenes by NMR. As already described in Section III.A, PrBe are deeply transported to the chain tail region in the bilayer core and the delivery site can be classified into category III [46]. Benzene, however, cannot deeply penetrate into the hydrophobic core, zone III, but is trapped preferentially at the interfacial site of the bilayer, zone II the delivery site can be classified into category II. Although benzene is generally considered to be hydrophobic, the delivery site of benzene determined by NMR is reasonable in the sense of the 7r-electrons with some affinity for the hydrophilic sites of the bilayer. Both drug and lipid sides of the H NMR spectra show that alkylbenzenes can deeply penetrate into the bilayer interior in the order PrBe > ethylbenzene > toluene > benzene, which is consistent with the sequence of the insolubility in water. 

Amphipathic peptides contain amino acid sequences that allow them to adopt membrane active conformations [219]. Usually amphipathic peptides contain a sequence with both hydrophobic amino acids (e.g., isoleucine, valine) and hydrophilic amino acids (e.g., glutamic acid, aspartic acid). These sequences allow the peptide to interact with lipid bilayer. Depending on the peptide sequence these peptides may form a-helix or j6-sheet conformation [219]. They may also interact with different parts of the bilayer. Importantly, these interactions result in a leaky lipid bilayer and, therefore, these features are quite interesting for drug delivery application. Obviously, many of these peptides are toxic due to their strong membrane interactions. 

New drug delivery systems are of great scientific and commercial interest. Amphiphilic networks composed of about 50/50 hydrophobic PIB and hydrophilic poly(2-(-dimethylamino)ethyl methacrylate) (DMAEMA) polymer segments were found to be biocompatible and to a large extent avascular (7). These PHM-PDMAEMA networks (i, in line with propositions of Weber and Stadler (2), and Sperling (J), denotes PDMAEMA chains linked by PIB chains) gave pH dependent... 

Drug Release from PHEMA-l-PIB Networks. Amphiphilic networks due to their distinct microphase separated hydrophobic-hydrophilic domain structure posses potential for biomedical applications. Similar microphase separated materials such as poly(HEMA- -styrene-6-HEMA), poly(HEMA-6-dimethylsiloxane- -HEMA), and poly(HEMA-6-butadiene- -HEMA) triblock copolymers have demonstrated better antithromogenic properties to any of the respective homopolymers (5-S). Amphiphilic networks are speculated to demonstrate better biocompatibility than either PIB or PHEMA because of their hydrophilic-hydrophobic microdomain structure. These unique structures may also be useful as swellable drug delivery matrices for both hydrophilic and lipophilic drugs due to their amphiphilic nature. Preliminary experiments with theophylline as a model for a water soluble drug were conducted to determine the release characteristics of the system. Experiments with lipophilic drugs are the subject of ongoing research. 

MB Charro, GI Vilas, TB Mendez, MAL Q, JP Marty, RH Guy. Delivery of a hydrophilic solute through the skin from novel microemulsion systems. Eur J Pharm Biopharm 43(l) 37-42, 1997. 

Another method of delivery of drug to the anterior segment of the eye that has proved successful is prodrug administration [144]. Since the corneal surface presents an effective lipoidal barrier, especially to hydrophilic compounds, it seems reasonable that a prodrug that is more lipophilic than the parent drug will be more successful in penetrating this barrier. 

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