Hydrophobic Drug Encapsulation

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... 

Fig. 30 Types of nanocarriers for drug delivery, (a) Polymeric nanoparticles polymeric nanoparticles in which drugs are conjugated to or encapsulated in polymers, (b) Polymeric micelles amphiphilic block copolymers that form nanosized core-shell structures in aqueous solution. The hydrophobic core region serves as a reservoir for hydrophobic drugs, whereas hydrophilic shell region stabilizes the hydrophobic core and renders the polymer water-soluble.

Nanospheres of PLGA were prepared by emulsion-evaporation by employing homogenization and a solvent system consisting of acetone in which both the drug and polymer were dissolved [95], The encapsulation of 5FU in these nanospheres was low compared to the more hydrophobic drug, indomethacin. It was reported that the hydrophilic 5FU leaked to the aqueous phase. PGL nanoparticles were prepared by aldol condensation loading 5FU with an efficiency of 14.32% [50]. 

Liu et al. (2003) recently applied classic Flory-Huggins solution theory to predict the solubility of the hydrophobic drug ellipticine in several block copolymers (Table 13.1). Solution theory predicted the solubility of ellipticine in block copolymers to be PBLAPCL> PDLA> PGA. Liu etal. found PEO-bPCLto encapsulate up to 21% w/w ellipticine, whereas PDLA encapsulated a maximum of 0.1% w/w. 

When the core is an oily liquid, the surrounding polymer is a single layer of polymer, and the vesicle is referred to as a nanocapsule. These systems have found utility in the encapsulation and delivery of hydrophobic drugs Polymers used for the formation of nanocapsules have typically included polyester homopolymers such as poly(D,L-lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA) and poly(caprolactone) PCL [112],... 

Figure 19.2 Schematic view of drug delivery with photosensitive liposomes and cyclodextrin cages (a) photoinduced lamellar-to-micellar phase transition in the liposome bilayer, (b) encapsulation of the drug (triangles) inside the liposome-containing photosensitizer (circles), (c) irradiation of the liposome, (d) drug release from the opened liposome, (e) hydrophobic photosensitizer encapsulated in a water-soluble cyclodextrin cage, and (f) liberation of the photosensitizer due to cleavage of the linker...

This technique, based on the precipitation of a hydrophobic polymer, is useful for the encapsulation of either hydrophilic or hydrophobic drugs because a variety of solvents, including polar (e.g., acetone or methanol) and non-polar (methylene chloride or chloroform) solvents can be chosen for dissolving the drug. This procedure is just like nanoprecipitation, however, the miscibility of both phases is prevented by the saturation of the external aqueous phase with PVA. Precipitation occurs when a sufficient amount of water is added to allow complete diffusion of the acetone into the aqueous phase. 

Silicone-based polymers bearing P-cyclodextrin as side chains have been prepared for the encapsulation of hydrophobic drugs that fit the cyclodextrin cavity. The example of the antifungal agent griseofulvin was detailed. 

Kojima et al. synthesized G3 and G4 PAMAM dendrimers with PEG grafts and examined their ability to encapsulate the hydrophobic drugs adriamycin and methotrexate. The modified PAMAM dendrimers were reported to have PEG grafted to every surface group and were estimated to have a hydrodynamic diameter of up to 14.7 nm. The purpose of the grafts... 

Phospholipids are essential components of cell membranes and liposomes, which are closed spherical vesicles with an inner aqueous core and an outer shell composed of phospholipid bilayer membranes. Depending on the level of hydrophobicity, moderately hydrophobic drugs can be solubilized by liposomes if the drug becomes encapsulated or intercalated within the liposome. The phospholipids in commercially available injectable formulations include hydrogenated soy phosphatidylcholine, dimyristoylphosphatidyl-choline, egg phosphatidylglycerol, distearoylphospha-tidylglycerol, and dimyristoylphosphatidylglycerol. 

Preparations of liposomes via SCF processing are designated as critical fluid liposomes (CFLs). CFLs have successfully encapsulated hydrophobic drugs such as taxoids, camptothecins, doxorubicin, vincristine, and cisplatin. In addition, stable paclitaxel liposomes with a size of 150-250 nm were obtained. Aphios Co. s patent (US Patent 5,776,486) on Super-Fluids CFL describes a method that is useful for the nanoencapsulation of paclitaxel and campothecin in aqueous liposomal formulations called Taxosomes and Camposomes , respectively. 

Using proprietary Superfluid CFL technology to prepare liposomes containing hydrophobic drugs. Taxosomes and Camposomes are nanometer-sized liposomes encapsulating taxol and camptothecin, respectively. 

---