Synthesis and characterization of an amphiphilic hyperbranched poly(amine‐ester)‐co‐D,L‐lactide (HPAE‐co‐PLA) copolymers and their nanoparticles for protein drug delivery

Abstract

A series of hyperbranched poly(amineester)-co-D,L-lactide (HPAE-co-PLA) copolymer were synthesized by ring-opening polymerization of D,L-lactide with Sn(Oct) 2 as catalyst to a fourth generation branched poly(amine-ester) (HPAE-OHs4). The chemical structures of copolymers were determined by FTIR, 1 H-NMR, 13C-NMR, and TGA. Double emulsion (DE) and nanoprecipitation (NP) method were used to fabricate the nanoparticles of these copolymers encapsulating bovine serum albumin (BSA) as a model. DSC thermo-grams indicated that the nanoparticles with BSA kept stable below 40 C. Different factors which influence on particular size and encapsulation efficiency (EE) were investigated. Their EE to BSA could reach 97.8% at an available condition. In vitro release behavior of NPs showed a continuous release after a burst release. The stability maintenance of BSA in the nanoparticle release in vitro was also measured via circular dichroism and fluorescence spectrometry. The results showed that the copolymer nanoparticles have a promising potential in protein delivery system.

Nanoparticle carriers based on copolymers of poly(ε-caprolactone) and hyperbranched polymers for drug delivery

“…HPAE-OHs were synthesized through a pseudo-one-step process by alcoholysis at 120°C using 1,1,1-trimethylol propane (as a molecular core) and N,N-diethylol-3-amine methylpropionate (as an AB 2 monomer) with Ti(OiPr) 4 as the catalyst [23][24][25]. The generation of HPAE-OHs was increased by repeatedly adding N,N-diethylol-3-amine methylpropionate monomer to the former generation product.…”

“…The cmc values of HPAE-co-PCL copolymer were listed in Table 2. From the Table 2, it can be seen that the cmc values of polymeric amphiphiles were lower than the critical micelle concentration (cmc) of low molecular weight surfactants [31] and other hyperbranched copolymers [24,25], indicating the stability of micelles from hyperbranched HPAE-co-PCL copolymer at dilute conditions. The increasing hydrophobicity by introduction of a large amount of hydrophobic groups further reduces the cmc values (Table 2).…”

“…The hydroxyl values of different generation HPAE-OHs were measured and calculated by the method described in the previous paper [24]. The molecular weights and polydispersity indexes of the HPAE-co-PCL copolymers were shown in Table 1.…”

Host–guest binding motifs based on hyperbranched polymers

“…124 A multi-nanoreservoir system can be formed by the DE method, while a single-layer nanosphere can be fabricated by the NP method. Hyperbranched poly(amine-ester) [124][125][126] and HPG 127,128 are the most widely used HBPs to encapsulated proteins. These protein-loaded HBPs showed enhanced encapsulation efficiency and the structural stability of protein was retained during the release process.…”

Production methods and stabilization strategies for polymer-based nanoparticles and microparticles for parenteral delivery of peptides and proteins

“…For example in a study by Ali and Lamprecht [31], PEG 400 was used as the organic phase for the preparation of Eudragit RL-BSA core/ shell-structured nanoparticles [31], which resulted in an EE of ~70%. In another study, hyperbranched poly(amine-ester) (HPAE)-co-poly(lactic acid) (PLA) nanoparticles with BSA encapsulated were produced by dissolving the protein in the aqueous phase instead of the organic phase [32], yielding an EE of ~60%. A similar EE was found for BSA and trypsin encapsulated in lactosylated poly(lactic-co-glycolic acid) (PLGA) by a comparable process.…”