Preparation and in vitro Evaluation of Linear and Star-branched PLGA Nanoparticles for Insulin Delivery

Abstract

Biodegradable nanoparticles, as drug delivery paradigms, have been extensively used for delivery of a wide range of small molecules as well as macromolecules, such as peptides, proteins, and genes. The morphological modification may improve the physicochemical characteristics of the biodegradable polymers. In the current investigation, the synthesis and characterization of linear, poly(D,L-lactide-co-glycolide) (PLGA)-poly(ethylene glycol) (PEG-PLGA), star-branched β-cyclodextrin-PLGA (β-CD-PLGA), and glucose-PLGA (Glu-PLGA) copolymers containing insulin as a model peptide drug have been reported. Linear and star-branched copolymers of PLGA were synthesized by bulk melt polymerization of the lactones (lactide and glycolide) in the presence of PEG, glucose, or β-CD using Sn-octoate as catalyst. Nanoparticles were prepared by a modified (w1/o/w 2) double emulsion method. Bovine insulin was successfully encapsulated into the linear and star-branched PLGA nanoparticles with retention of insulin stability and the nanoparticles preparation process was optimized to reduce the burst effect and provide in vitro sustained release. The average particle size of samples was 120—355 nm. The cumulative amount of 65—84% insulin was released from the samples after 24 days. The yield of encapsulation of insulin was superior to 95%. Based on these findings, it is suggested that the novel PLGA nanoparticles can be used as a carrier for prolonged delivery of protein—peptide drugs.

Shikonin-loaded antibody-armed nanoparticles for targeted therapy of ovarian cancer

“…[16][17][18] Given the fact that biodegradable polymeric NPs elicit negligible side effects, they have been widely investigated for efficient and safe delivery of encapsulated/entrapped chemotherapeutics to the target cells. 17 Of these, poly(lacticco-glycolic acid) (PLGA) is the most studied polymer; [19][20][21] it is also a safe biocompatible polymer in comparison with synthetic polymers/lipids used as delivery systems. [22][23][24] PLGA polymer has previously been used for delivery of insulin 21 and doxorubicin (Adriamycin).…”

“…17 Of these, poly(lacticco-glycolic acid) (PLGA) is the most studied polymer; [19][20][21] it is also a safe biocompatible polymer in comparison with synthetic polymers/lipids used as delivery systems. [22][23][24] PLGA polymer has previously been used for delivery of insulin 21 and doxorubicin (Adriamycin). 19 In the current work, we aimed to engineer SHK-loaded, surface-modified PLGA NPs (eg, SHK-loaded, polyethylene glycol [PEG] …”

“…In comparison with toxic non-biodegradable polymer-/ lipid-based drug delivery systems, 22,[31][32][33][34] biodegradable polymers such as PLGA appear to be a safer biocompatible system for delivery of anticancer agents. 17,19,21 In the current study, we capitalized on the engineering of Ab-armed PEGylated PLGA NPs for delivery of SHK, which is known as cytostatic, cytotoxic and immunomodulatory secondary metabolite in a concentration-dependent manner.…”

Self-assembled nanomicelles using PLGA–PEG amphiphilic block copolymer for insulin delivery: a physicochemical investigation and determination of CMC values

“…Appropriate solubilization of insulin as well as low initial burst release are the main factors in the development of nanomicelles containing insulin. There are some reports in the literature revealing the efforts on optimization of the above two parameters [12,23] but there still needs to do more for obtaining better and reasonable results.…”

A fluorescence-based assay for octreotide in kinetic release from depot formulations

“…4 To date, there is no official monograph for octreotide acetate in the main (US, European, British, and Brazilian) pharmacopeias. A depot formulation for intramuscular injection, based on polymeric microparticles comprising branched star-glucose PLGA [5][6][7] (US5922682) became available in the 1990', which allowed the continued release of the octreotide for up to one month (US5538739). 7 With the proximity of patent expiration (2011 for some countries), pharmaceutical laboratories are becoming motivated in the development of a generic or similar formulation (US2010086597).…”