Block copolymer micelles as long-circulating drug vehicles

Patha, Aravind Sai; Patil, Tanvi; Pandey, Pinki; Kuche, Kaushik; Ghadi, Rohan; Jain, Sanyog

doi:10.1016/b978-0-323-91248-8.00008-8

Cited by 6 publications

(10 citation statements)

References 114 publications

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“…PEG is a hydrophilic, polyether, biocompatible, nontoxic polymer with strong surface adherence property, suitable in functionalization of various nanoparticles like silica, polystyrene, and so forth. [41][42][43] PEGylation (Table 1) involves functionalizing the nanoparticles by the formation of covalent and noncovalent bonds. PEG imparts stealth properties to nanoparticles by formation of an intermittent barrier layer between nanoparticulate surface and the external environment.…”

Section: Pegmentioning

confidence: 99%

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Evasion of opsonization of macromolecules using novel surface‐modification and biological‐camouflage‐mediated techniques for next‐generation drug delivery

Mehta,

Shende

2023

Cell Biochemistry & Function

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Opsonization plays a pivotal role in hindering controlled drug release from nanoformulations due to macrophage‐mediated nanoparticle destruction. While first and second‐generation delivery systems, such as lipoplexes (50–150 nm) and quantum dots, hold immense potential in revolutionizing disease treatment through spatiotemporal controlled drug delivery, their therapeutic efficacy is restricted by the selective labeling of nanoparticles for uptake by reticuloendothelial system and mononuclear phagocyte system via various molecular forces, such as electrostatic, hydrophobic, and van der Waals bonds. This review article presents novel insights into surface‐modification techniques utilizing macromolecule‐mediated approaches, including PEGylation, di‐block copolymerization, and multi‐block polymerization. These techniques induce stealth properties by generating steric forces to repel micromolecular‐opsonins, such as fibrinogen, thereby mitigating opsonization effects. Moreover, advanced biological methods, like cellular hitchhiking and dysopsonic protein adsorption, are highlighted for their potential to induce biological camouflage by adsorbing onto the nanoparticulate surface, leading to immune escape. These significant findings pave the way for the development of long‐circulating next‐generation nanoplatforms capable of delivering superior therapy to patients. Future integration of artificial intelligence‐based algorithms, integrated with nanoparticle properties such as shape, size, and surface chemistry, can aid in elucidating nanoparticulate‐surface morphology and predicting interactions with the immune system, providing valuable insights into the probable path of opsonization.

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Section: Pegmentioning

confidence: 99%

Section: Polymersmentioning

confidence: 99%

Evasion of opsonization of macromolecules using novel surface‐modification and biological‐camouflage‐mediated techniques for next‐generation drug delivery

Mehta,

Shende

2023

Cell Biochemistry & Function

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“…The opsonization process for polymersomes can vary depending on variables such as route of administration, biological events, surface coating, charge, and particle size. The molecular weight, surface concentration, and molecular conformation of the hydrophilic block, predominantly PEG, determine the surface coating of polymersomes. ,− Polymersomes are reportedly taken up by the liver. However, modifying the surface charge of polymersomes to a slightly negative or positive charge can affect the protein binding and circulation time. , The charge and size of polymersomes can significantly impact the fate of nanoparticles.…”

Section: Introduction To Amphiphilic Block Copolymersmentioning

confidence: 99%

Amphiphilic Block Copolymer Nanostructures as a Tunable Delivery Platform: Perspective and Framework for the Future Drug Product Development

Sinsinbar,

Bindra,

Liu

et al. 2024

Biomacromolecules

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Nanoformulation of active payloads or pharmaceutical ingredients (APIs) has always been an area of interest to achieve targeted, sustained, and efficacious delivery. Various delivery platforms have been explored, but loading and delivery of APIs have been challenging because of the chemical and structural properties of these molecules. Polymersomes made from amphiphilic block copolymers (ABCPs) have shown enormous promise as a tunable API delivery platform and confer multifold advantages over lipid-based systems. For example, a COVID booster vaccine comprising polymersomes encapsulating spike protein (ACM-001) has recently completed a Phase I clinical trial and provides a case for developing safe drug products based on ABCP delivery platforms. However, several limitations need to be resolved before they can reach their full potential. In this Perspective, we would like to highlight such aspects requiring further development for translating an ABCP-based delivery platform from a proof of concept to a viable commercial product.

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“…Polymeric micelles formed from polycaprolactone (PCL)-based amphiphilic diblock copolymers can be employed in drug delivery applications due to their biocompatibility and (bio)degradability. ( Shah and Vasava, 2019 ; Ahmad Shariff et al, 2022 ; Kuperkar et al, 2022 ; Bhadran et al, 2023a ; Patha et al, 2023 ). The micelles can physically pack poorly water-soluble drugs in their hydrophobic core and stabilize them in aqueous solutions with the help of their hydrophilic shell.…”

Section: Introductionmentioning

confidence: 99%

Effect of aromatic substituents on thermoresponsive functional polycaprolactone micellar carriers for doxorubicin delivery

Wang,

Polara,

Bhadran

et al. 2024

Front. Pharmacol.

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Amphiphilic functional polycaprolactone (PCL) diblock copolymers are excellent candidates for micellar drug delivery. The functional groups on the backbone significantly affect the properties of PCL. A systematic investigation of the effect of aromatic substituents on the self-assembly of γ-functionalized PCLs and the delivery of doxorubicin (DOX) is presented in this work. Three thermoresponsive amphiphilic diblock copolymers with poly(γ-benzyloxy-ε-caprolactone) (PBnCL), poly(γ-phenyl- ε-caprolactone) (PPhCL), poly(γ-(4-ethoxyphenyl)-ε-caprolactone) (PEtOPhCL), respectively, as hydrophobic block and γ-tri(ethylene glycol) functionalized PCL (PME3CL) as hydrophilic block were prepared through ring-opening polymerization (ROP). The thermoresponsivity, thermodynamic stability, micelle size, morphology, DOX-loading, and release profile were determined. The LCST values of amphiphilic diblock copolymers PME3CL-b-PBnCL, PME3CL-b-PPhCL, and PME3CL-b-PEtOPhCL are 74.2°C, 43.3°C, and 37.3°C, respectively. All three copolymers formed spherical micelles in phosphate-buffered saline (PBS, 1×, pH = 7.4) at low concentrations ranging from 8.7 × 10−4 g/L to 8.9 × 10−4 g/L. PME3CL-b-PBnCL micelles showed the highest DOX loading capacity of 3.01 ± 0.18 (wt%) and the lowest drug release, while PME3CL-b-PEtOPhCL micelles exhibited the lowest DOX loading capacity of 1.95 ± 0.05 (wt%) and the highest drug release. Cytotoxicity and cellular uptake of all three micelles were assessed in vitro using MDA-MB-231 breast cancer cells. All three empty micelles did not show significant toxicity to the cells at concentrations high up to 0.5 mg/mL. All three DOX-loaded micelles were uptaken into the cells, and DOX was internalized into the nucleus of the cells.

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Block copolymer micelles as long-circulating drug vehicles

Cited by 6 publications

References 114 publications

Evasion of opsonization of macromolecules using novel surface‐modification and biological‐camouflage‐mediated techniques for next‐generation drug delivery

Evasion of opsonization of macromolecules using novel surface‐modification and biological‐camouflage‐mediated techniques for next‐generation drug delivery

Amphiphilic Block Copolymer Nanostructures as a Tunable Delivery Platform: Perspective and Framework for the Future Drug Product Development

Effect of aromatic substituents on thermoresponsive functional polycaprolactone micellar carriers for doxorubicin delivery

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