Modulating drug release from poly(lactic-co-glycolic acid) thin films through terminal end-groups and molecular weight

Huang, Charlotte L.; Kumar, Saranya; Tan, John J. Z.; Boey, Freddy Yin Chiang; Venkatraman, Subbu S.; Steele, Terry W. J.; Loo, Say Chye Joachim

doi:10.1016/j.polymdegradstab.2012.11.012

Cited by 32 publications

(18 citation statements)

References 39 publications

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“…Moreover, they are recognized as an inherently robust platform since the film-forming polymer acts as a flexible carrier for the drug particles. More importantly, it was shown that the polymer films offer a promising delivery platform for poorly soluble drugs, leading to numerous papers on the incorporation of poorly water-soluble drugs into polymer films [4,7,8,[10][11][12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Impact of Mixing on Content Uniformity of Thin Polymer Films Containing Drug Micro-Doses

et al. 2021

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The impact of mixer type and critical process parameters (CPPs) on critical quality attributes (CQAs), including the drug content uniformity (CU) of slurry-cast polymer films loaded with micro-sized poorly water-soluble drugs were investigated. Previously untested hypothesis was that the best mixer at suitable CPPs promotes uniform drug dispersion within film precursors leading to acceptable dried-film CU at low, ~0.6 wt% drug concentrations. Taguchi design was utilized to select the best of three mixers; low-shear impeller, high-shear planetary, and high-intensity vibrational, for dried-film drug concentration of ~23 wt%. As-received fenofibrate, a model poorly water-soluble drug (~6 µm) was directly mixed with the hydroxypropyl methylcellulose (HPMC) and glycerin aqueous solution. Impeller and planetary mixers yielded desirable film relative standard deviation (RSD), while vibrational mixer could not. For the lowest dried-film drug concentration of ~0.6 wt%, only planetary mixer yielded RSD <6%. The precursor drug homogeneity was a sufficient but not a necessary condition for achieving dried-film RSD <6%. Thus, proper selection of mixer and its CPPs assured desirable film CQAs. However, minor drug particle aggregation was identified via re-dispersion testing which also led to incomplete drug release.

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Section: Introductionmentioning

confidence: 99%

Impact of Mixing on Content Uniformity of Thin Polymer Films Containing Drug Micro-Doses

et al. 2021

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“…The in-situ crosslinking processes and swelling behavior of fibrin glue were found to be challenging for the hydrated tissue environment [ 7 ]. Tissue adhesives need to be able to bond both natural materials and synthetic films for applications involving implantable biosensors and drug depots [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. Formation of covalent bonds between thin film or hydrogel adhesive formulations and soft tissue substrates is a promising strategy to achieve a reliable adhesion strength [ 3 , 15 , 16 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

On-Demand Bioadhesive Dendrimers with Reduced Cytotoxicity

et al. 2018

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Tissue adhesives based on polyamidoamine (PAMAM) dendrimer, grafted with UV-sensitive aryldiazirine (PAMAM-g-diazirine) are promising new candidates for light active adhesion on soft tissues. Diazirine carbene precursors form interfacial and intermolecular covalent crosslinks with tissues after UV light activation that requires no premixing or inclusion of free radical initiators. However, primary amines on the PAMAM dendrimer surface present a potential risk due to their cytotoxic and immunological effects. PAMAM-g-diazirine formulations with cationic pendant amines converted into neutral amide groups were evaluated. In vitro toxicity is reduced by an order of magnitude upon amine capping while retaining bioadhesive properties. The in vivo immunological response to PAMAM-g-diazirine formulations was found to be optimal in comparison to standard poly(lactic-co-glycolic acid) (PLGA) thin films.

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“…Our laboratory has previously published on both high-throughput drug release measurements and on tuning the drug release of fluorescein diacetate in polyester thin film using acidic terminal end-groups to control the rate of degradation [ 14 , 15 , 16 ]. However, the measurement of valganciclovir in drug release studies has only been conducted with time-consuming analytical methods such as HPLC.…”

Section: Introductionmentioning

confidence: 99%

High Throughput Screening of Valganciclovir in Acidic Microenvironments of Polyester Thin Films

et al. 2015

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Ganciclovir and valganciclor are antiviral agents used for the treatment of cytomegalovirus retinitis. The conventional method for administering ganciclovir in cytomegalovirus retinitis patients is repeated intravitreal injections. In order to obviate the possible detrimental effects of repeated intraocular injections, to improve compliance and to eliminate systemic side-effects, we investigated the tuning of the ganciclovir pro-drug valganciclovir and the release from thin films of poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), or mixtures of both, as a step towards prototyping periocular valganciclovir implants. To investigate the drug release, we established and evaluated a high throughput fluorescence-based quantification screening assay for the detection of valganciclovir. Our protocol allows quantifying as little as 20 ng of valganciclovir in 96-well polypropylene plates and a 50× faster analysis compared to traditional HPLC measurements. This improvement can hence be extrapolated to other polyester matrix thin film formulations using a high-throughput approach. The acidic microenvironment within the polyester matrix was found to protect valganciclovir from degradation with resultant increases in the half-life of the drug in the periocular implant to 100 days. Linear release profiles were obtained using the pure polyester polymers for 10 days and 60 days formulations; however, gross phase separations of PCL and acid-terminated PLGA prevented tuning within these timeframes due to the phase separation of the polymer, valganciclovir, or both.

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Modulating drug release from poly(lactic-co-glycolic acid) thin films through terminal end-groups and molecular weight

Cited by 32 publications

References 39 publications

Impact of Mixing on Content Uniformity of Thin Polymer Films Containing Drug Micro-Doses

Impact of Mixing on Content Uniformity of Thin Polymer Films Containing Drug Micro-Doses

On-Demand Bioadhesive Dendrimers with Reduced Cytotoxicity

High Throughput Screening of Valganciclovir in Acidic Microenvironments of Polyester Thin Films

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