Nanocontainers Formed by Self-Assembly of Poly(ethylene oxide)-b-poly(glycerol monomethacrylate)−Drug Conjugates

Abstract

The synthesis, self-assembly behavior, and delivery properties of poly(ethylene oxide)-b-poly-(glycerol monomethacrylate)-(PEO-b-PG2MA-) drug conjugates is herein described. Double hydrophilic PEOb-PG2MA copolymers synthesized by atom transfer radical polymerization (ATRP), using a PEO-based macroinitiator, were used for post-polymerization conjugation to the hydrophobic nonsteroidal anti-inflammatory agent indomethacin (IND). IND contents ranging from 15 to 49% w/w p were attached to the same polymer precursor via Steglich esterification, leading to amphiphilic block copolymer-drug conjugates (PEO-b-(PG2MA-IND)). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) experiments revealed that PEO-b-(PG2MA-IND) copolymer chains self-assemble into spherical nanoparticles in water, whose hydrodynamic size (2R H ) 24-100 nm) and morphology (micelles or vesicles) are dictated by both the amount of IND and the PG2MA block length. Interestingly, such a particular system was also proven to be able to stabilize, transport and deliver physically encapsulated (free) IND (F-IND). The maximum F-IND loadings ranged from 13 to 20% w/w p , thus reaching remarkable IND payloads (i.e., covalently bound B-IND + physically entrapped F-IND) as high as 58% w/w p . However, self-organization for F-IND loaded samples with more than 50% w/w p IND originated vesicular morphologies instead of micelles and provoked a huge increase in the size of the objects. The release of IND is a pH-dependent process, which is governed by intrinsic molecular characteristics of F-IND (aqueous dissociation behavior) and pH-sensitivity of ester linkages in the conjugates. At approximately neutral pH, the ester bound linkages are stable and the diffusion of F-IND out of the carrier is favored, whereas sustained release with slow kinetics takes place under acidic pH conditions.

Preparation of Polymeric Micelles of Poly(Ethylene Oxide-b-Lactic Acid) and their Encapsulation With Lavender Oil

“…33 The radius of gyration (Rg) was calculated from the elastic part (I(q)) of the scattering intensity using the Guinier approximation as follows, where I is the scattering intensity and I 0 is the scattering intensity at q = 0 (equation 3). …”

“…38 In fact, the nanoparticles obtained from the PEO 5KDa -b-PLA 4.5KDa copolymer (lower PLA content) were significantly larger than those obtained from the PEO 5KDa -b-PLA 10KDa system, suggesting a dependence on the PEO. 33 The size distribution and polydispersity of the nanoparticle suspensions were evaluated considering the angular dependence associated with the light scattering intensity. Considering that the nanoparticle suspensions are in permanent movement, the fluctuation intensity of the scattered light is directly related to Brownian movement.…”

Elucidation of Acceleration Mechanisms by a Photosensitive Onium Salt for Nitroxide-Mediated Photocontrolled/Living Radical Polymerization

“…The controlled/living radical polymerization (CLRP) has been an indispensable technique to design and create highly functional and efficient materials supporting today's cutting-edge technologies in many fields, such as drug and gene deliveries [1]- [4] and anti-bacterial treatment [5] in medical care, photolithography in electronics [6]- [8], water purification in environmental engineering [9], and surface modifications of wettability in the textile and vehicle industries [10]- [12]. The significance of the CLRP is the improvement of the functions by unifying the physical properties based on strict control of the molecular weight related to the structure of the polymers.…”

Biodegradable polymersomes for drug delivery : circulation kinetics and biodistribution, modulated drug delivery and cellular uptake

“…Degradable polymers undergo hydrolytic cleavage of their ester or carbonate linkages in the main chains with a rate of hydrolysis depending on the character of the block, the molecular weight of the block, the pH and sometimes the presence of enzymes [78][79][80][81]. Poly (acrylic acid) (PAA) [60,62,82], poly(L-glutamic acid) (PGA) [31,63,71,83] and PEG [11,12,18,41,48,74,76,77,[84][85][86][87][88] have been frequently selected as water-soluble blocks. PEG has been used most frequently as a hydrophilic block because of the resistance it provides in surface layers to blood protein adsorption [89][90][91][92][93].…”

“…Ps based on PEG-b-poly(2,4,6-trimethoxybenzylidenepentaerythritol carbonate) (PEG-PTMBPEC) were reported by Chen et al and in vitro studies demonstrated that the release of paclitaxel (PTX) as well as doxorubicin (DOX) from these Ps was faster at mildly acidic conditions than at physiological pH due to the faster degradation of PTMBPEC at mildly acidic conditions [12]. The pH-dependent release of indomethacin (IND) from Ps based on PEGb-poly(glycerol monomethacrylate)-IND conjugates (PEG-(PG2MA-IND)) was also demonstrated [85]. IND was bound to the copolymer via an ester bond and rapid release of IND was detected at acidic conditions, owing to hydrolysis of ester bonds.…”