Thermosensitive poly(N-isopropyl acrylamide-co-N,N-dimethyl acryl amide)-block-poly(d,l-lactide) amphiphilic block copolymer micelles for prednisone drug release

Abstract

Novel amphiphilic block copolymers consisting of hydrophobic poly(D,L-lactide) segments and hydrophilic poly(N-isopropylacrylamide-co-N, N-dimethylacrylamide) blocks were designed and synthesized through a simple free radical copolymerization route based on a bifunctional initiator, followed by the ring-opening polymerization of D,L-lactide. The copolymers self-assembled into thermosensitive spherical-nanosized core–shell micelles in aqueous solution in the presence or the absence of the model drug prednisone. The chemical and physical characterizations of drug-loaded and unloaded micelles revealed a lower critical solution temperature of 40°C–47°C, and a critical micelle concentration less than 7.20 mg L−1, a transmission electron microscope mean particle size from 50 to 75 nm, and a narrow dynamic light scattering diameter below 180 nm. The prepared blank and drug-loaded micellar nanoparticles were thermodynamically stabile and employed in targeted drug delivery by responding to the higher temperature of the local microenvironment. Based on prednisone release kinetic studies, structural changes of the self-assembled micelles as well as temperature- or environment-induced diffusion controlled drug release and improved bioavailability. The copolymer micelles exhibited good biocompatibility as established by the MTT cytotoxicity assay. Therefore, an effective target therapy against lesion tissues is feasible using these polymeric micelles.

Thermo-triggered drug delivery from polymeric micelles of poly(N-isopropylacrylamide-co-acrylamide)-b-poly(n-butyl methacrylate) for tumor targeting

“…The cell viability is slightly higher for cells exposed to MTX-loaded micelles as compared to cells exposed to free MTX at 37°C. Similar findings were also reported by Chung et al 41 and Xu et al 17 It seems that the cellular uptake mechanism is different for micelles and the free drug. 41 The surface of the micelles changed from hydrophilic to hydrophobic above their LCST as shown above by the in vitro attachment experiments.…”

“…Site-specific drug release upon local heating requires the drugs to be loaded into a thermo-sensitive polymer matrix with a LCST between 37°C and 43°C. 16 Many hydrophilic comonomers with structures similar to isopropylacrylamide (NIPAAm), such as N,N′-dimethylacrylamide (DMAAm), 17 N-hydroxymethylacrylamide (HMAAm), 18 acrylic acid (AA), 15 and acrylamide (AAm), were copolymerized to adjust the LCST of the copolymers. 16 Many hydrophilic comonomers with structures similar to isopropylacrylamide (NIPAAm), such as N,N′-dimethylacrylamide (DMAAm), 17 N-hydroxymethylacrylamide (HMAAm), 18 acrylic acid (AA), 15 and acrylamide (AAm), were copolymerized to adjust the LCST of the copolymers.…”

“…14 By adjusting the nature of comonomers, it is possible to fine-tune the corresponding LCST and the sharpness of thermo-response. 16 Many hydrophilic comonomers with structures similar to isopropylacrylamide (NIPAAm), such as N,N′ -dimethylacrylamide (DMAAm), 17 N -hydroxymethylacrylamide (HMAAm), 18 acrylic acid (AA), 15 and acrylamide (AAm), were copolymerized to adjust the LCST of the copolymers. 16,19–21 The relationship between the inverse of the LCST of the polymer solution and the polymer volume fraction ( β ) is linear for NIPAAm copolymers in the experimental range of 0.65 < β < 1.…”

Synthesis and characterization of β-cyclodextrin-conjugated alginate hydrogel for controlled release of hydrocortisone acetate in response to mechanical stimulation

“…Cytotoxicity of either blank Alg-β-CD or Alg-β-CD loaded with HCA was assessed with MTT viability assay to mouse fibroblasts (L929). 26 Briefly, the lyophilized blank Alg-β-CD and Alg-β-CD loaded with HCA (Alg/β-CD-EDA = 27/23 in both cases) were sterilized by UV radiation for about 1 day on each side. Afterwards, the hydrogels were immersed (10 mg/mL) in a complete DMEM containing 10% FBS and placed in an incubator at 37°C for 48 h. Then, the remaining medium was extracted and stored at 4°C before use.…”

Biodegradable uniform microspheres based on solid-in-oil-in-water emulsion for drug delivery: A comparison of homogenization and fluidic device

“…There are many encapsulation methods suitable for each drug type. 6–9 For example, oil-in-water (O/W) emulsification methods are commonly used for hydrophobic drugs due to their high solubility in organic solvents. 10 In the cases of hydrophilic and insoluble drugs, water-in-oil-in-water (W/O/W) and solid-in-oil-in-water (S/O/W) emulsification methods have often been used in an effort to improve encapsulation efficiency and control drug release.…”