Dynamics of<i>in vitro</i>polymer degradation of polycaprolactone-based scaffolds: accelerated versus simulated physiological conditions

Lam, Christopher; Savalani, M. M.; Teoh, Swee‐Hin; Hutmacher, Dietmar W.

doi:10.1088/1748-6041/3/3/034108

Cited by 389 publications

(378 citation statements)

References 26 publications

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“…Unlike GB-PLGA and IgG-PLA, the release of lomustine from PCL in PBS was not studied long term. This is due to PCL's slow degradation rate, estimated at two to four years depending on the starting molecular weight [122][123][124]. Therefore, a method capable of accelerating the release of lomustine from PCL was investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, a method capable of accelerating the release of lomustine from PCL was investigated. These options included enzymatic, thermal, and base-promoted hydrolytic degradation [123,124].…”

Section: Discussionmentioning

confidence: 99%

“…Due to PCL's potential for long-term degradation, up to two to four years, an accelerated study was conducted using 5 M NaOH-DMSO 65-35 (v/v), as shown in Figure 3.13 [122][123][124]. Since lomustine degrades in aqueous solutions, the degradation rate of free lomustine in both PBS and 5 M NaOH-DMSO was determined (Figure 3.12) and applied as a correction to the release of lomustine from PCL microspheres.…”

Section: In Vitro Release Of Lomustine From Pcl Microspheresmentioning

confidence: 99%

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Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Floyd

Galperin

Ratner

2015

J Biomedical Materials Res

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Departments of Bioengineering and Chemical EngineeringThe grim prognosis for patients diagnosed with malignant gliomas necessitates the development of new therapeutic strategies for localized and sustained drug delivery to combat tumor drug resistance and regrowth. Here we introduced the novel formulation of drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy (DREAM BIG Therapy) that is applied post-resection. DREAM BIG Therapy consists of three types of microspheres [poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA), and poly(ε-caprolactone) (PCL)] containing various encapsulated chemotherapeutics, suspended in a degradable, aqueous poly(Nisopropylacrylamide) (PNIPAM) solution. The thermoresponsive PNIPAM solution is capable of suspending drug encapsulated microspheres at room temperature which can be "sprayed on" the post-surgical site. The physiological temperature of the treatment site (37°C) would cause PNIPAM solution to solidify and form an adherent gel layer with entrapped microspheres, providing intimate contact with remaining tumor cells. Over time, PLGA (rapid degradation), PLA (medium speed degradation), and then PCL (slow degradation) microspheres would break iv down, releasing their drug payloads in a sequential, multi-drug release directly to the tumor site, addressing cancerous regrowth and tumor drug resistance. This dissertation will address the development of DREAM BIG Therapy, from microsphere formulation to pilot in vivo studies.Initial work focused on developing blank and drug encapsulated microspheres using emulsion techniques. Preliminary studies utilized rhodamine B as a model drug for encapsulation in PLGA, PLA, and PCL particles and optimized formulation parameters to achieve a high encapsulation. Then, gefitinib, IgG, and lomustine were encapsulated in PLGA, PLA, and PCL microspheres, respectively, achieving encapsulation efficiencies greater than 80% and drug loadings greater than 0.3%. The in vitro release of gefitinib and IgG were also studied. Gefitinib released from PLGA microspheres over 40 days while the release of IgG from PLA microspheres was slower, over a year long period.The microsphere-PNIPAM system was tested for aerosolized application ex vivo. The aqueous PNIPAM solution suspended the microspheres and was aerosolized before phase transitioning to an adherent gel layer on the tissue, entrapping the microspheres on the tissue surface. Finally, when tested in vivo, the gefitinib encapsulated PLGA microspheres entrapped in PNIPAM slowed the tumor volume growth of a subcutaneous C6 glioma in comparison to blank PLGA microspheres entrapped in PNIPAM. Overall, this research confirms the potential of DREAM BIG therapy for future use with multiple chemotherapeutics and microsphere types to combat gliomas at a localized site.v

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: In Vitro Release Of Lomustine From Pcl Microspheresmentioning

confidence: 99%

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Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Floyd

Galperin

Ratner

2015

J Biomedical Materials Res

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“…The degradation rate of degradable polymers is controlled by numerous factors such as degree of crystallinity, chemical structure, molecular weight, porosity, surface/volume ratio, manufacturing methods, implantation site, applied load, degradation temperature and pH of the degradation medium [34][35][36][37]. The degradation temperature has a significant influence on the degradation of biodegradable polymers.…”

Section: Introductionmentioning

confidence: 99%

In vitro degradation and mechanical properties of PLA-PCL copolymer unit cell scaffolds generated by two-photon polymerization

et al. 2016

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The manufacture of 3D scaffolds with specific controlled porous architecture, defined microstructure and an adjustable degradation profile was achieved using two-photon polymerization (TPP) with a size of 2 × 4 × 2 mm3. Scaffolds made from poly(D,L-lactide-co-ɛ-caprolactone) copolymer with varying lactic acid (LA) and ɛ -caprolactone (CL) ratios (LC16:4, 18:2 and 9:1) were generated via ring-opening-polymerization and photoactivation. The reactivity was quantified using photo-DSC, yielding a double bond conversion ranging from 70% to 90%. The pore sizes for all LC scaffolds were see 300 μm and throat sizes varied from 152 to 177 μm. In vitro degradation was conducted at different temperatures; 37, 50 and 65 °C. Change in compressive properties immersed at 37 °C over time was also measured. Variations in thermal, degradation and mechanical properties of the LC scaffolds were related to the LA/CL ratio. Scaffold LC16:4 showed significantly lower glass transition temperature (Tg) (4.8 °C) in comparison with the LC 18:2 and 9:1 (see 32 °C). Rates of mass loss for the LC16:4 scaffolds at all temperatures were significantly lower than that for LC18:2 and 9:1. The degradation activation energies for scaffold materials ranged from 82.7 to 94.9 kJ mol−1. A prediction for degradation time was applied through a correlation between long-term degradation studies at 37 °C and short-term studies at elevated temperatures (50 and 65 °C) using the half-life of mass loss (Time (M1/2)) parameter. However, the initial compressive moduli for LC18:2 and 9:1 scaffolds were 7 to 14 times higher than LC16:4 (see 0.27) which was suggested to be due to its higher CL content (20%). All scaffolds showed a gradual loss in their compressive strength and modulus over time as a result of progressive mass loss over time. The manufacturing process utilized and the scaffolds produced have potential for use in tissue engineering and regenerative medicine applications.

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“…PEG also enhances the stability of biomolecules and affects release characteristics [17]. In addition, if PCL is the predominant polymer in the fabricated electrospun fibers, diffusion through the polymeric matrix is expected to be the major mechanism [18]. The aim of this work was to fabricate fibrous scaffolds from a polymeric blend of PCL and PEG with an incorporated model drug, in order to create a drug delivery system (DDS), which would enable encapsulation and sustained delivery of the pharmaceutical agent.…”

Section: Introductionmentioning

confidence: 99%

Pcl/Peg Electrospun Fibers as Drug Carriers for the Controlled Delivery of Dipyridamole

Repanas¹,

Wf²,

O³

et al. 2015

J In Silico In Vitro Pharmacol

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Electrospinning is a versatile and diverse technology for the production of nano-and microfibers that can be used as a drug delivery system (DDS). The aim of this study was to create fibrous scaffolds from a mixture of polycaprolactone (PCL) and polyethylene glycol (PEG) and to evaluate the suitability of the fibers as DDS. Dipyridamole (DPA), an anti-thrombotic and anti-proliferative pharmaceutical agent, was used as a model drug. Two types of PEG with different chain length were used. The structural, mechanical and physicochemical characteristics of the fibers with and without DPA, were determined, and the release kinetics of DPA were studied. The obtained fibers loaded with DPA and with the higher molecular weight PEG were smooth and had an average diameter of 586.75 ± 204.79 nm and an average Young's modulus of 57.14 ± 4.35 MPa, whereas the tensile strain at break was 0.61 ±0.05 mm/mm and the ultimate tensile strength (UTS) was 16.79 ± 3.08 MPa. The cumulative release of DPA revealed two stages: an initial burst phenomenon followed by slower Fickian diffusion (release exponent n = 0.432).

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Dynamics ofin vitropolymer degradation of polycaprolactone-based scaffolds: accelerated versus simulated physiological conditions

Cited by 389 publications

References 26 publications

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

Drug encapsulated aerosolized microspheres as a biodegradable, intelligent glioma therapy

In vitro degradation and mechanical properties of PLA-PCL copolymer unit cell scaffolds generated by two-photon polymerization

Pcl/Peg Electrospun Fibers as Drug Carriers for the Controlled Delivery of Dipyridamole

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