Peptide Delivery

Recently, colloidal carrier systems, especially nanoparticles, have been receiving much attention in the field of drug targeting because of their high loading capacity for drugs, particularly macromolecules, as well as their unique disposition characteristics in the body [143, 144]. It is well known that the bioavailability of peptide and protein drugs after oral administration is very low because of their instability in the gastrointestinal (GI) tract and low permeability through the intestinal mucosa [145, 146]. Therefore, injectable dosage forms are currently used to obtain therapeutic effects. Due to poor compliance of these administration routes, it is indispensable to develop alternatives such as nasal, buccal, rectal, vaginal, pulmonary, and transdermal routes [147]. Oral administration is the most convenient route for drug delivery, and several approaches such as chemical modification to alter the physicochemical properties of peptide drugs [148], the use of an absorption enhancer to promote drug absorption [149-151], and the use of a protease inhibitor to protect drugs against degradation by enzymes [150] have been investigated in order to achieve oral peptide delivery. Many pharmaceutical scientists have also reported that particulate drug delivery systems such as nanoparticles [152-154], microcapsules [153, 155], liposomes [156], and emulsions [157] are useful in improving the absorption of peptide drugs via the GI tract.

Much of the research has focused on the absorption enhancement of peptide and protein drugs and vaccine antigens. Couvreur and co-workers have been studying whether nanoparticles composed of polyalkylcyanoacrylate derivatives enhance the absorption of orally administered insulin, using animal models [158-161]. They found that insulin encapsulated in polyisobutylcyanoacrylate nanocap-sules reduced glycemia by 50-60%, although free insulin did not affect glycemia when administered orally to diabetic rats. Kawashima et al. [162] reported that the absorption of elca-tonin, which is a calcitonin of eel, via the GI tract of rats was enhanced by poly(-lactide-glycolide) nanoparticles coated with chitosan, which is a mucoadhesive cationic polymer. They also studied the effect of chitosan-coated liposomes on the intestinal absorption of insulin in rats and reported that the blood glucose concentration decreased significantly after oral administration of insulin-loaded liposomes [163]. Sakuma et al. also demonstrated that nanoparticles composed of novel graft copolymers having a hydrophobic backbone and hydrophilic branches can improve the absorption of salmon calcitonin in rats [164-167].

In general, absorption of a drug via the GI tract is closely related to its solubility. Many drugs with poor absorption characteristics are highly water-soluble and this high polarity causes the low permeability through the intestinal membrane which is mainly composed of hydrophobic lipids. Numerous peptide and protein drugs fall into this category [168-170]. There are two ways to incorporate a hydrophilic drug in a nanoparticle. One is to encapsulate it into the nanoparticle core and the other is to adsorb it onto the nanoparticle surface [170].

0 0

Post a comment