Recent developments in micellar drug carriers featuring substituted poly(ε-caprolactone)s

Amphiphilic diblock copolymers bearing histone deacetylase inhibitors (HDACi) (4-phenyl butyric acid and valproic acid) were synthesized by the ring-opening polymerization of γ-4-phenylbutyrate-ε-caprolactone (PBACL), γ-valproate-ε-caprolactone (VPACL), and ε-caprolactone (CL) from a poly(ethylene glycol) macroinitiator (PEG). These amphiphilic diblock copolymers self-assembled into stable pro-drug micelles and demonstrated excellent biocompatibility. High loading of doxorubicin (DOX) up to 5.1 wt% was achieved. Optimized micelles enabled sustained drug release in a concentration-dependent manner over time to expand the therapeutic window of cytotoxic small molecule drugs.

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“…To date a large number of functionalized poly(ε-caprolactone)s have been reported for drug delivery applications. 26–29 …”

Section: Resultsmentioning

confidence: 99%

HDAC inhibitor conjugated polymeric prodrug micelles for doxorubicin delivery

et al. 2017

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“…Poly(ε‐caprolactone)s (PCLs) are an essential class of synthetic polymers widely used as biomaterials for medical devices, drug delivery and tissue engineering, as shape‐memory polymers, adhesives, and soft segments for polyurethane synthesis as well as in packaging and micro‐electronics . Such extensive application of PCLs is possible as a result of their tailorable mechanical properties, miscibility with a large range of other polymers and biodegradability . PCLs are hydrophobic, semi‐crystalline and have low melting points (typically 60 °C).…”

Section: Introductionmentioning

confidence: 99%

“…Functional groups have often been added to render PCLs more hydrophilic, adhesive, or biocompatible to diversify their applications, or for subsequent coupling or crosslinking reactions toward different macromolecular structures. The methodology for introduction of pendant functional groups along PCL chains consists of the synthesis and polymerization of functional CL substituted at the α‐ or γ‐position by a large series of functional groups such as halogen, acid, acyloxy, alcohol, amine, allyl, or an ATRP initiating group . Usually a multi‐step process involving protection and de‐protection of functional groups before and after polymerization was necessary, since the functional groups may coordinate with metal catalysts .…”

Section: Introductionmentioning

confidence: 99%

Synthesis of allyl end‐block functionalized poly(ε‐caprolactone)s and their facile post‐functionalization via thiol–ene reaction

Truong

Thai

Nguyên

et al. 2017

J. Polym. Sci. Part A: Polym. Chem.

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A simple and facile strategy for the functionalization of commercial poly(ε‐caprolactone) diols (PCLs) with pendant functionalities at the polymer chain termini is described. Well‐defined allyl‐functionalized PCLs with varying numbers of allyl end‐block side‐groups were synthesized by cationic ring‐opening polymerization of allyl glycidyl ether using PCL diols as macroinitiators. Further functionalization of the allyl‐functionalized PCLs was realized via the UV‐initiated radical addition of a furan‐functionalized thiol to the pendant allyl functional groups, showing the suitability for post‐modification of the PCL materials. Changes in polymer structure as a result of varying the number of pendant functional units at the PCL chain termini were demonstrated. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 928–939

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“…1-3 However, PCL degrades extremely slowly in vitro and in vivo due to its intrinsic hydrophobicity and crystallinity. 3,11 Basically, there are two approaches to functional poly(ε-caprolactone)s including postpolymerization modification and ring-opening polymerization (ROP) of substituted caprolactone monomers. In order to overcome these limitations, many reactive groups, like hydroxyl, 6, 7 carboxylic 6, 8 and amino groups, 9,10 have been introduced onto the PCL chain with the aim for regulating its physico-chemical and biological properties, such as hydrophilicity, biodegradation rate and bioadhesion.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of well-defined carboxyl poly(ε-caprolactone) by fine-tuning the protection group

Zhang

Xiao

et al. 2016

Polym. Chem.

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Introduction of reactive groups such as -NH2, -COOH etc onto poly(ε-caprolactone) (PCL) backbone was necessary for further modification but remained as a challenge of synthetic chemistry with a well-controlled approach. Carboxyl functionalized PCL was typically prepared via three steps involving synthesis of the corresponding monomer with a carboxyl-protecting group, polymerization and removal of the protection. Except for obtaining purified monomers and a decent polymerization, the most critical step in carboxyl PCL synthesis was deprotection from a degradable main chain. Therefore, electronic effect and steric hindrance of the protecting group were taken into account with the aim for controllable polymerization and feasible deprotection. Substituents including -CH3, H and NO2 with discriminative electronegativity on the para position of the benzyl protecting group have been selected to investigate their behavior in monomer preparation, polymerization and deprotection, respectively. It turned out that electron donating group (-CH3) displayed highest selectivity in monomer preparation, excellent control over polymerization degree and most efficient removal of protecting groups without the degradation of the backbone. In addition, the reactivity of pendant carboxyl groups on PCL was demonstrated by amidation with 4-amino-2,2,6,6-tetramethylpiperidinyloxy (4-amino-TEMPO). Our results also provide guidance information on preparing well-defined biodegradable polymers with pendant reactive groups such as polypeptides, expanding the library of novel biomaterials.

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Recent developments in micellar drug carriers featuring substituted poly(ε-caprolactone)s

Abstract: Synthetic modification of caprolactone monomers and polymers provides a route to self-assembling block copolymers for use in drug carrier applications.

Cited by 93 publications

References 71 publications

HDAC inhibitor conjugated polymeric prodrug micelles for doxorubicin delivery

HDAC inhibitor conjugated polymeric prodrug micelles for doxorubicin delivery

Synthesis of allyl end‐block functionalized poly(ε‐caprolactone)s and their facile post‐functionalization via thiol–ene reaction

Synthesis of well-defined carboxyl poly(ε-caprolactone) by fine-tuning the protection group

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