Nanoparticles made of microbial poly(gamma-glutamate)s for encapsulation and delivery of drugs and proteins.
This study focused on the preparation and evaluation of nanoparticles made of alkyl esters of microbial poly(gamma-glutamic acid) (PGGA) to be used as drugs and proteins carrier and delivery systems. Racemic PGGA of bacterial origin was fully methylated or partially esterified to render non-water-soluble polymers. A set of co-polymers containing poly(glutamic acid) and ethyl, hexyl, dodecyl and octadecyl glutamate units with alkyl contents of 50 and 75% was prepared. Spherical nanoparticles with a diameter of 200-250 nm and a narrow distribution were generated from the alkylated polymers by the precipitation-dialysis method. These nanoparticles readily degraded hydrolytically upon incubation in simulated physiological medium at a rate dependent on the alkylation degree and the length of the alkyl group. All these nanoparticles were able to encapsulate efficiently erythromycin. Those made of carboxyl containing polyglutamates were also effective to load alpha-chymotrypsin. The release of such compounds from nanoparticles upon incubation proceeded essentially following the same profile that is followed in the hydrolysis of the corresponding substrate polymers. The loss of enzyme activity of the incubated protein diminished significantly upon encapsulation in these systems.
Portilla-Arias
José A
JA
Departament d'Enginyeria Química, Universitat Politècnica de Catalunya, ETSEIB, Diagonal 647, 08028 Barcelona, Spain.
Camargo
Beatriz
B
García-Alvarez
Montserrat
M
de Ilarduya
Antxon Martínez
AM
Muñoz-Guerra
Sebastián
S
D000478:Alkylation; D000818:Animals; D001412:Bacillus subtilis / Q000737:chemistry*; D002417:Cattle; D002918:Chymotrypsin / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004917:Erythromycin / Q000737:chemistry / Q000378:metabolism; D004951:Esterification; D006868:Hydrolysis; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000138:chemical synthesis / Q000737:chemistry; D011506:Proteins / Q000008:administration & dosage*; D012995:Solubility; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry
D004337:Drug Carriers; D011506:Proteins; C511775:poly(gamma-glutamic acid); D014867:Water; D011099:Polyglutamic Acid; D004917:Erythromycin; D002918:Chymotrypsin; C117608:alpha-chymotrypsin