Nanoformulation of auraptene with tb and pb biocompatible amphiphilic copolymers
,1,* Gholamreza dehghan
,2 Roya salehi
1. Drug applied research centre, Tabriz University of Medical Sciences,Tabriz, Iran
2. Faculty of natural sciences, University of Tabriz, Tabriz, Iran
3. Drug applied research centre, Tabriz University of Medical Sciences,Tabriz, Iran
The most abundant prenyl oxycumarin in the nature is granyl oxy-coumarin or aur(auraptene), which is well known today for many valuable pharmaceutical properties including: high anti-cancer, antimicrobial, anti-fungal, anti-inflammatory, antioxidant, anti-hypertension properties.poor water solubility of natural compounds, is one of the most important obstacles for drug delivery.in recent years, nanoscience, specially nano-size drug carriers has been widespread in order to increase the efficacy and bioavailability of drugs.
in this study, two, three block (tb) and penta block (pb) biodegradable copolymers were synthesized to prepare the appropriate carriers for delivery of aur
2.materials and methods
2.1 synthesis of copolymers
pentablock copolymer: poly (ethylene glycol)-poly (caprolactone)-poly (lactic acid) (pla-pcl-peg-pcl-pla), for preparation of nanocarriers was synthesized in two steps.
calculated amounts of peg mw1,000 (7.5g), ε-caprolactone (15 ml), and stannous octoate (1 wt%) were added in the round-bottomflask and degassed for 30 min. then the flask was purged with nitrogen, and the reaction was performed for 24 h at 130 °c. the resulting crude product was dissolved in methylene chloride and precipitated with cold petroleum ether to remove un-reacted monomers. after purification predetermined amount of triblock copolymer (5 g) and l-lactide (10 ml) monomer were added in the round-bottom flask, and stannous octoate(1 wt %) was added as a catalyst. then, the flask was purged with nitrogen, and a reaction was performed for 24 h at 130 °c. the final product was purified as was said above.
2.3. drug loading and efficiency
drug-polymer solution was added dropwise to deionized water solution of 0.25% pva while hemogenizing at 20000 rpm. then nanoparticles solutions were centrifuged at 12000 rpm for 1 hour and the supernatant was removed. the nanoparticle solutions were centrifuged twice more to eliminate organic solvent completely and then diluted with deionized water.
nanoformulated auraptene prepared with three proportion of the drug to the polymers.
then uv–vis spectrophotometer was applied to measure the amount of unloaded aur.
uv absorbance for aur was measured at ƛmax = 310 nm.
the encapsulation efficiency and loading capacity of aur on tb and pb nanocarriers were calculated by following equations:
encapsulation efficiency(%)=(w of initial drug-w of free drug)/(w of initial drug)×100
2.4.dynamic light scattering
to measure the average diameter and zeta-potential of nanoparticles, the laser scattering
technique was used at 25 °c.
2.5. scanning electron microscopy
the surface morphology and size of nanocarriers were observed by field emission microscop. particles size were achieved by measuring the diameters of at least 50 particles revealed through sem.
3.1.s size measurment
approximately the actual size of particle is 5 to 10 times smaller than the hydrodynamic size.
the greater surface charge and small size of the particles causes the suspension stablility and also causes penetration into the tissues and high intracellular uptake. in the images of sem, nanoparticles have spherical morphology and size of the nanoparticles varies from 10 nm to 50 nm.
3.3. auraptene loading result
loading capacity and loading efficiency parameteres of 3 types of formulation were measured. pb polymer prepared nanocarriers entrapment efficiency is more than 90 % in all types of formulations.maximum entrapment efficiency of pb prepared nanocarriers is 95 %.tb polymer prepared nanocarriers entrapment efficiency has increased from 71% in 1to10 drug polymer ratio to 89% in 1to5 ratio and then to 94% in 1 to 2 ratio.
in this study nanoformulation of aur was done for the firs time. prepared nanocarriers were desirable for delivery of aurapten in terms of size, pdi ,surface charge, morphology and loading efficiency parameters. also our findings showed the superioroty of pb copolymer to tb in delivery of auraptene.
Auraptene, nanoformulation.tb and pb copolymers