Encapsulation hydrophilic drugs

In an attempt to encapsulate hydrophilic drugs (e.g., peptides and proteins), the following alternative methods have been proposed ... 

Modification of the conventional SEDDS led to the development of SDEDDS to provide great opportunity for overcoming bioavailability challenges for BCS class III drugs (Qi et al., 2011). On dilution, these systems produce w/o/w-type fine double thermodynamic stable emulsions, which can encapsulate hydrophilic drugs in the inner aqueous phase. Generally, SDEDDS are a mixture of hydrophilic surfactant and w/o emulsions and may also contain some viscosity modifiers and stabilizers. Qi et al. (2011) demonstrated a nearly 2.56-fold increased absorption of pidotimod when encapsulated in SDEDDS vis-a-vis the pidotimod solution. 

Liposomes are very attractive as components of DDSs since they may encapsulate hydrophilic drugs in their aqueous core, while the liposomal bilayer may solubilize hydrophobic substances. Liposomes are the most clinically established nanometer-scale delivery systems of cytotoxic and antifungal drugs, genes, vaccines, and imaging agents. The cationic polymers may play different roles in the liposomal DDSs. 

Figure 37.3 Liposomes. Liposomes are small artificial vesicles that are formed when phospholipids and water are subjected to high-shear mixing or to vigorous agitation by an ultrasonic probe. Liposomes can be used to encapsulate hydrophilic drugs and are used for the delivery of some anticancer drugs. They are also used to deliver cosmetics.

Nanosize particles of polyacrylic acid were synthesized in w/o microemulsions using azobisisobutyronitrile as lipophilic radical initiator, which were considered suitable for encapsulation of peptides and other hydrophilic drugs [195],... 

Fig. 1 Schematic illustration of a liposome encapsulating a hydrophilic drug. The membrane contains phospholipid and cholesterol molecules. (Reprinted with permission from Ref. 3 with slight modification. Copyright 1998 Adis International.)... 

Weidenauer, U., Bodmeier, D., and Kissel,T. (2003), Microencapsulation of hydrophilic drug substances using biodegradable polyesters. Part I Evaluation of different techniques for the encapsulation of pamidronate di-sodium salt, J. Microencapsul., 20, 509-524. 

Ethanol Injection Small unilamellar vesicles (with diameter of 30 nm) can be prepared with the ethanol injection technique [128], Lipids are dissolved in ethanol and injected rapidly in the aqueous solution under stirring (final concentrations up to 7.5% (v/v) ethanol can be applied).The method is very easy, having the advantage of avoiding chemical or physical treatment of lipids. However, there is an extra step to remove ethanol and the concentration of vesicles produced is rather low. Also encapsulation of hydrophilic drugs is also low, due to the high volumes used. 

A liquid crystal is a general term used to describe a variety of anisotropic structures formed by amphiphilic molecules, typically but not exclusively at high concentrations. Hexagonal, lamellar, and cubic phases are all examples of liquid crystalline phases. These phases have been examined as drug delivery systems because of their stability, broad solubilization potential, ability to delay the release of encapsulated drug, and, in the case of lamellar phases, their ability to form closed, spherical bilayer structures known as vesicles, which can entrap both hydrophobic and hydrophilic drug. This section will review SANS studies performed on all liquid crystalline phases, except vesicles, which will be considered separately. Vesicles will be considered separately because, with a few exceptions, generally mixed systems, vesicles (unlike the other liquid crystalline phases mentioned) do not form spontaneously upon dispersal of the surfactant in water and because there have been many more SANS studies performed on these systems. 

Water-soluble drugs cannot be encapsulated with the 0/W-emulsion technique because the drug would be lost to the external aqueous phase. Two methods have been described for the encapsulation of hydrophilic drugs one is based on using an external oil phase and the other one on the formation of the microparticles by a w/o/w-melt dispersion technique. 

Key words DRV, Protein, Peptide, Hydrophilic drug. Encapsulation yield. Vaccine, DNA, Particulate, Bacteria, Cyclodextrin... 

From 1984, when they were first developed, DRV liposomes have been used for liposomal encapsulation of various active substances which may be divided into three main categories (1) Low MW drug molecules (mainly hydrophilic drugs) (3-20) (2) Proteins or peptides and enzymes (21-26), and (3) DNA or oligonucleotides (26-32). From these categories, the last two are primarily used as liposomal vaccines. Some examples of substances entrapped in DRV liposomes from the last 10 year literature are presented in Table 1. 

In this section of the chapter, the general methodology used to encapsulate any type of material (mostly applying for hydrophilic drugs, peptides or proteins) will be described in detail. 

For convenience in the assay, calcein was used as a hydrophilic drug stand-in. It registers the fraction of the aqueous entrapped phase and hence provides a good measure of how much of a hydrophilic drug would be encapsulated by echo-genic liposomes. 

Liposomes are predominantly used as carriers for hydrophilic molecules that are encapsulated within the aqueous inner volume which is confined by the lipid bilayer. These molecules generally do not interact with the lipid moiety of the vesicle. Long circulating liposomes modified with poly (ethylene glycol) (PEG) and other formulations carrying encapsulated cytotoxic drugs such as doxoru-bicine, paclitaxel, vincristine, lurtotecan and others are clinically approved chemotherapeutic liposome formulations (1-5). 

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