Stimuli-Induced Architectural Transition as a Tool for Controlling the Enzymatic Degradability of Polymeric Micelles

Slor, Gadi; Tevet, Shahar; Amir, Roey J.

doi:10.1021/acspolymersau.2c00023

Cited by 8 publications

(4 citation statements)

References 43 publications

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“…As a control, we also monitored the enzymatic degradation of micelles made from only DBA, which showed faster degradation (Figures S18 and S19), providing further support for the formation of mixed micelles when the two types of amphiphiles are mixed. The results, which are in good agreement with our previous report of splittable TBA 49 and gemini amphiphiles, 50 indicate that the DBA could rapidly exchange between the micellar and unimer states, thus being highly accessible to the activating enzyme. 51 On the other hand, the higher molecular weight and architecture of the TBA, as was also described by Lodge and Bates for other TBAbased assemblies, 52,53 made the TBA exchange significantly slower and hence nearly unaffected by the degrading enzyme during the initial micellar state.…”

Section: T H Isupporting

confidence: 92%

Architecture-Based Programming of Polymeric Micelles to Undergo Sequential Mesophase Transitions

et al. 2023

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Di-and triblock amphiphiles can form different mesophases ranging from micelles to hydrogels depending on their chemical structures, hydrophilic to hydrophobic ratios, and their ratio in the mixture. In addition, their different architectures dictate their exchange rate between the assembled and unimer states and consequently affect their responsiveness toward enzymatic degradation. Here we report the utilization of the different reactivities of diand triblock amphiphiles, having exactly the same hydrophilic to lipophilic balance, toward enzymatic degradation as a tool for programming formulations to undergo sequential enzymatically induced transitions from (i) micelles to (ii) hydrogel and finally to (iii) dissolved polymers. We show that the rate of transition between the mesophases can be programmed by changing the ratio of the amphiphiles in the formulation, and that the hydrogels can maintain encapsulated cargo, which was loaded into the micelles. The reported results demonstrate the ability of molecular architecture to serve as a tool for programming smart formulations to adopt different structures and functions.

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Section: T H Isupporting

confidence: 92%

Architecture-Based Programming of Polymeric Micelles to Undergo Sequential Mesophase Transitions

et al. 2023

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“…When looking at the HPLC vial (Figure 1g), the formation of hydrogel was clearly observed, explaining the rapid decrease in TBA concentration. These results, which are in good agreement with our previous report of splittable TBA 47 and gemini-amphiphiles, 48 indicate that the DBA could rapidly exchange between the micellar and unimer states, thus being highly accessible to the activating enzyme. 49 On the other hand, the higher molecular weight and architecture of the TBA, as was also described by Lodge and Bates for other TBA based assemblies, 50,51 made the TBA exchange significantly slower and hence nearly unaffected by the degrading enzyme during the initial micellar state.…”

supporting

confidence: 92%

Polymeric architecture as a tool for programming sequential enzyme-induced mesophase transitions

Rathee

Edelstein-Pardo

Sitt

et al. 2022

Preprint

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Di- and tri-block amphiphiles can form different mesophases ranging from micelles to hydrogels depending on their chemical structures, hydrophilic to hydrophobic ratios, and their ratio in the mixture. In addition, their different architectures dictate their exchange rate between the assembled and unimer states, and consequently affect their responsiveness towards enzymatic degradation. Here we report the utilization of the different reactivities of di- and tri-block amphiphiles towards enzymatic degradation as a tool for programming formulations to undergo three sequential enzymatically induced transitions from: (i) micelles to (ii) hydrogel and finally to (iii) dissolved polymers. We show that the rate of transition between the mesophases can be programmed by changing the ratio of the amphiphiles in the formulation, and that the hydrogels can maintain encapsulated cargo, which was loaded into the micelles. The reported results demonstrate the ability of molecular architecture to serve as a tool for programming smart formulations to adopt different structures and functions.

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“…The in vitro release of DEX from the hydrogel-forming MN arrays was determined using PBS (pH 7.4) solution containing 1 mg/mL bovine serum albumin (BSA), which exhibits an affinity to hydrophobic entities. − Porcine liver esterase (PLE) was used as a model for esterase activity. Briefly, Tri-C9MNs with 10% w/w 35 kDa were placed in GeBaFlex tubes (8 MWCO kDa) containing 0, 15, or 45 μM of PLE enzyme, and then the tube was immersed in 40 mL of the release medium (PBS containing BSA).…”

Section: Materials and Methodsmentioning

confidence: 99%

Hydrogel Microneedles with Programmed Mesophase Transitions for Controlled Drug Delivery

Dawud,

Edelstein-Pardo,

Mulamukkil

et al. 2024

ACS Appl. Bio Mater.

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Microneedle-based drug delivery offers an attractive and minimally invasive administration route to deliver therapeutic agents through the skin by bypassing the stratum corneum, the main skin barrier. Recently, hydrogel-based microneedles have gained prominence for their exceptional ability to precisely control the release of their drug cargo. In this study, we investigated the feasibility of fabricating microneedles from triblock amphiphiles with linear poly(ethylene glycol) (PEG) as the hydrophilic middle block and two dendritic side-blocks with enzyme-cleavable hydrophobic end-groups. Due to the poor formation and brittleness of microneedles made from the neat amphiphile, we added a sodium alginate base layer and tested different polymeric excipients to enhance the mechanical strength of the microneedles. Following optimization, microneedles based on triblock amphiphiles were successfully fabricated and exhibited favorable insertion efficiency and low height reduction percentage when tested in Parafilm as a skin-simulant model. When tested against static forces ranging from 50 to 1000 g (4.9–98 mN/needle), the microneedles showed adequate mechanical strength with no fractures or broken segments. In buffer solution, the solid microneedles swelled into a hydrogel within about 30 s, followed by their rapid disintegration into small hydrogel particles. These hydrogel particles could undergo slow enzymatic degradation to soluble polymers. In vitro release study of dexamethasone (DEX), as a steroid model drug, showed first-order drug release, with 90% released within 6 days. Eventually, DEX-loaded MNs were subjected to an insertion test using chicken skin and showed full penetration. This study demonstrates the feasibility of programming hydrogel-forming microneedles to undergo several mesophase transitions and their potential application as a delivery system for self-administration, increased patient compliance, improved efficacy, and sustained drug release.

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Stimuli-Induced Architectural Transition as a Tool for Controlling the Enzymatic Degradability of Polymeric Micelles

Cited by 8 publications

References 43 publications

Architecture-Based Programming of Polymeric Micelles to Undergo Sequential Mesophase Transitions

Architecture-Based Programming of Polymeric Micelles to Undergo Sequential Mesophase Transitions

Polymeric architecture as a tool for programming sequential enzyme-induced mesophase transitions

Hydrogel Microneedles with Programmed Mesophase Transitions for Controlled Drug Delivery

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