Enhanced oral absorption of salmon calcitonin-encapsulated PLGA nanoparticles by adding organic substances

Abstract

Two organic compounds with potential absorption enhancing effects, bile acids and transferrin, were examined by the gastro-intestinal (GI) absorption of therapeutic salmon calcitonin (sCT) as encapsulated by poly(lactide-co-glycolide) (PLGA) for the treatment of osteoporosis. The sCT-loaded PLGA nanocapsules were prepared by O/W emulsification approach. Either additive of a designated content was mixed with sCT dissolved in methanol. For bile acids, their content (0-7.5 mg to sCT 6 mg) was observed to have a substantial effect both on the emulsification process and the encapsulation efficiency. When 1.5 mg of bile acids was added, sCT-loaded PLGA nanocapsules of about 700 nm in diameter and with a fairly high encapsulation efficiency greater than 35% were produced. Accordingly, this formulation gave the most significant hypocalcemic effect in an in vivo experiment with SD rats. On the other hand, a too high bile acids loading resulted in a poor encapsulation efficiency of less than 7%. Two principal roles of bile acids were proposed: emulsifying agent and absorption enhancer. Transferrin, a human glycoprotein of 80 kDa molecular weight, turned out to have potential as absorption enhancer as well.

Salmon calcitonin-loaded Eudragit® and Eudragit®-PLGA nanoparticles:in vitroandin vivoevaluation

“…The particle sizes of all nanoparticle formulations decreased with the addition of NaTDC in the formulation due to its surfactant nature (p 5 0.05). Similar results were reported by Jung et al (2009). The zeta potentials of nanoparticles are given in Table 2.…”

“…This observation might be due to the used NaTDC amount and the ratio of drug:NaTDC and indicates that further research will need to investigate the optimum ratio of sCT to NaTDC for the enhancement of intestinal sCT absorption from the chosen nanoparticle formulation in terms of appropriate in vitro characteristics and hypocalcemic effect in this study. Similar results were reported by previous studies (Song et al, 2001(Song et al, , 2005Jung et al, 2009). Song et al (2005) showed that using proliposomes containing sCT and sodium taurodeoxycholate enhanced the intestinal absorption of sCT.…”

“…As indicated in Table 2, the encapsulation efficiencies of nanoparticle formulations had a negative relationship with the addition of NaTDC (p 5 0.05). Jung et al (2009) used bile salts of various contents (0.75-7.5 mg) for the preparation of sCT-loaded PLGA nanoparticles and showed that the EE of nanoparticles significantly decreased with increases in the amount of bile acid in formulations. They also reported that bile acids were very active as emulsifiers during the emulsification process, but not as active as an interfacial barrier in preventing sCT molecules from diffusing into the water phase.…”

“…Thus, coupling of drugs to the selective absorption of bile salts is a useful way to improve the bioavailability of drugs. Bile salts also increase the paracellular and transcellular transport by disturbing tight junctions in the epithelial lining (Samstein et al, 2008;Jung et al, 2009).…”

Functional PLGA NPs for Oral Drug Delivery: Recent Strategies and Developments

“…Jung et al (2009) [74] compared the effects of increased amounts of bile salts in NPs for the oral delivery of salmon calcitonin, measuring their hypocalcemic effect in rats. Particles, 1000-240 nm in diameter, were synthetized by a double w 1 /o/w 2 emulsion method.…”