Polymersomes: Soft Nanoparticles from Miktoarm Stars for Applications in Drug Delivery

Abstract

Self-assembly of amphiphilic macromolecules has provided an advantageous platform to address significant issues in a variety of areas, including biology. Such soft nanoparticles with a hydrophobic core and hydrophilic corona, referred to as micelles, have been extensively investigated for delivering lipophilic therapeutics by physical encapsulation. Polymeric vesicles or polymersomes with similarities in morphology to liposomes continue to play an essential role in understanding the behavior of cell membranes and, in addition, have offered opportunities in designing smart nanoformulations. With the evolution in synthetic methodologies to macromolecular precursors, the construction of such assemblies can now be modulated to tailor their properties to match desired needs. This review brings into focus the current state-of-the-art in the design of polymersomes using amphiphilic miktoarm star polymers through a detailed analysis of the synthesis of miktoarm star polymers with tuned lengths of varied polymeric arms, their self-assembly, and applications in drug delivery.

Stimuli‐Responsive Miktoarm Polymer‐Based Formulations for Fisetin Delivery and Regulatory Effects in Hyperactive Human Microglia

“…The developments in this nanotechnology for medicine are facilitated by introducing versatility in compositions of such soft nanoparticles which can help resolve key issues in nanocarrier‐based drug delivery. [ 22 ] In this study, we aimed to prepare fisetin (a flavonol with a broad spectrum of biological activity but with challenges in its administration due to poor aqueous solubility) loaded stimuli‐responsive nanoformulations and evaluate, for the first time, regulatory effects of fisetin in human microglia. Our synthetic design strategy was based on i) utilizing a combination of efficient Steglich esterification, ring opening polymerization, and copper‐catalyzed alkyne‐azide cycloaddition “click” (CuAAC) chemistry; and ii) incorporating stable but endogenous stimuli active chemical entities into the polymer architecture.…”

“…[ 12–15 ] There are examples of miktoarm polymer‐based polymersomes (vesicles) in drug delivery, [ 16–21 ] and a detailed analysis of their compositions and comparisons with linear diblock‐copolymer analogs has recently been reviewed. [ 22 ] Polymersomes have a number of similarities with intracellular vesicles and those pinching off plasma membranes. [ 23–25 ] A significant amount of effort continues to be devoted to designing nanocarriers (micelles and polymersomes) from linear amphiphilic diblock copolymers.…”

Proteinosomes via Self-Assembly of Thermoresponsive Miktoarm Polymer Protein Bioconjugates

“…The structure of this bioconjugate is similar to a miktoarm star copolymer. The self-assembly behavior of the miktoarm star copolymer is different from the linear one. − In the miktoarm star copolymer, several different polymer chains are connected at one point. The steric hindrance and the interactions between polymer chains greatly affect the self-assembly.…”

Single Functional Group Platform for Multistimuli Responsivities: Tertiary Amine for CO2/pH/ROS-Triggered Cargo Release in Nanocarriers

“…Polymeric nanoparticles (NPs) have advanced a viable approach in delivering poorly water-soluble drugs, reducing their undesired toxicity, and helping facilitate clinical translation. − To enhance the efficacy of drug delivery nanotechnologies, significant emphasis has been placed on exploiting pathological alterations at disease locations including low pH, elevated reactive oxygen species (ROS) concentrations, higher temperatures, and so forth by incorporating selective chemical entities into their macromolecular precursors to achieve targeted delivery. − Such nanocarriers typically respond well to specific endogenous cues to enhance drug release. , Due to insufficient biological understanding and complex double-edged behavior of biologically active gases, studies on gas-responsive polymers for drug delivery are progressing at a relatively slow pace. − As a regulator of blood pH, CO 2 exists mainly in three different forms in the body: in a hydrated state (HCO 3 – ), bound to hemoglobin (carbamate), and as dissolved CO 2 . At disease sites, especially tumor, the build-up of CO 2 (hypercapnia) tends to be associated with acidosis and hypoxia, which can confer chemoresistance in lung cancer cells, as well as aggravate pancreatic cancer. , On top of that, the overproduction of ROS, such as hydrogen peroxide (H 2 O 2 ), superoxide (O 2 – ), hydroxy radicals (•OH), and singlet oxygen ( 1 O 2 ) can cause dysfunctions that can be observed in pathologies such as cardiovascular and neurodegenerative diseases, diabetes, and aging. − As such, changes in CO 2 , pH, and ROS concentrations constitute important markers in the microenvironments at disease sites.…”