ABSTRACT
A conjugate of the antihypertensive drug, lisinopril, with triblock poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) copolymer was synthesized by the reaction of PLA-PEG-PLA copolymer with lisinopril in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. The conjugated copolymer was characterized in vitro by hydrogen nuclear magnetic resonance (HNMR), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) techniques. Then, the lisinopril conjugated PLA-PEG-PLA were self-assembled into micelles in aqueous solution. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM). The results revealed that the micelles formed by the lisinopril-conjugated PLA-PEG-PLA have spherical structure with the average size of 162 nm. The release behavior of conjugated copolymer, micelles and micelles physically loaded by lisinopril were compared in different media. In vitro release study showed that in contrast to physically loaded micelles, the release rate of micelles consisted of the conjugated copolymer was dependent on pH of media where it was higher at lower pH compared to the neutral medium. Another feature of the conjugated micelles was their more sustained release profile compared to the lisinopril-conjugated copolymer and physically loaded micelles.
Subject(s)
Drug Carriers , Drug Delivery Systems , Polyesters , Polyethylene Glycols , MicellesABSTRACT
Nanoparticles have outstanding compensate compared with other drug carriers, as a result of their small particle size and bulky and changeable surface. Recently, block copolymers have get imaginary movement on the continuing research in the area of drug delivery technology, because of their potential to afford a biomaterial having an extensive series of amphiphilic personality, in addition to targeting the drugs to specific position. Block copolymers are prepared up of blocks of different polymerized monomers. Between the block copolymers, amphiphilic block copolymers can self-assemble to form nano-sized vehicles, for example micelles, liposomes, polymerases and hydrogels in aqueous or non-aqueous media. This review evaluated the synthesis, construction, and major applications of amphiphilic block copolymer and analogous vehicles in order to provide an overview of the present features of functionalized block copolymers for drug delivery applications.
Subject(s)
Drug Delivery Systems/methods , Nanoparticles/chemistry , Polymers/chemistry , Polymers/chemical synthesis , Biodegradable Plastics/chemistryABSTRACT
Enalapril was used for hypertension and congestive heart failure. Di-block mPEG-PCL copolymers were synthesized and used to prepare of polymersomes for controlled release of enalapril as a hydrophilic drug. The various methods such as HNMR, FTIR, GPC, DSC, PCS and AFM performed for characterization of the polymersomes. The results of AFM showed that the polymersomes had spherical structure and the size of nanoparticles was 97 nm. Drug-loading efï¬ciency of nanoparticles from copolymers with compositions of mPEG1-PCL1, mPEG2-PCL2, and mPEG3-PCL3 were 14.43%, 19.8%, and 12.33% respectively. The release profile of enalapril for drug loaded nanoparticles prepared from mPEG3-PCL3 was very fast and release profile for the nanoparticles prepared from mPEG1-PCL1 and mPEG2-PCL2 was sustained. The IC50 value of enalapril was determined to be 8 µM while EPM/m-PEG-PCL nanoparticles did not show significant toxicity at equal concentrations in comparison with enalapril drug. Therapeutic preparations of mPEG-PCL micelle are calibrated by the mouse LD50 assay. A dose-finding scheme of the polymeric micelle showed a safe dose of mPEG-PCL micelles was approximately 330 mg/kg in mice. The relationship between the numbers of animals, number of doses, duration of the assay used to estimate the LD50 and the precision of the assay were investigated. Overall, the results was showed that m-PEG-PCL polymersomes can be considered as a promising carrier for hydrophilic drugs.
Subject(s)
Drug Carriers/chemistry , Enalapril/administration & dosage , Enalapril/pharmacology , Micelles , Nanoparticles/chemistry , Nanoparticles/toxicity , Polyesters/chemistry , Polyethylene Glycols/chemistry , Animals , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Carriers/administration & dosage , Drug Carriers/chemical synthesis , Drug Carriers/toxicity , Drug Liberation , Drug Stability , Enalapril/pharmacokinetics , Humans , Inhibitory Concentration 50 , Leukocytes, Mononuclear/drug effects , Mice , Nanoparticles/administration & dosage , Particle Size , Polyesters/administration & dosage , Polyesters/chemical synthesis , Polyesters/toxicity , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/chemical synthesis , Polyethylene Glycols/toxicity , Primary Cell CultureABSTRACT
Tri-block poly(lactide)-poly(ethylene glycol)-poly(lactide) (PLA-PEG-PLA) copolymers were synthesized and used to prepare polymersomes loaded separately by the hydrophobic and hydrophilic model drugs, atorvastatin and lisinopril, respectively. The resulting nanostructures were characterized by various techniques such as FTIR, DSC, PCS and AFM. The polymersomes exhibited high encapsulation efficiencies of almost 78% and 70.8% for atorvastatin and lisinopril, respectively. Investigation on FTIR and DSC results revealed that such a high encapsulation efficiency is due to strong interaction between atorvastatin and the copolymer. The impact of drug/copolymer ratio and copolymer composition on drug-loading efficiency and drug release behavior were also studied. The results showed that in case of lisinopril, polymersomes exhibited a triphasic drug release, while for atorvastatin a biphasic release profile was obtained. Overall, the results indicated that PLA-PEG-PLA polymersomes can be considered as a promising carrier for both hydrophilic and hydrophobic drugs.
