Injectable, long-acting PLGA formulations: Analyzing PLGA and understanding microparticle formation

Park, Kinam; Skidmore, Sarah; Hadar, Justin; Garner, John; Park, Haesun; Otte, Andrew; Soh, Bong Kwan; Yoon, Gwangheum; Di-jia, YU; Yun, Yeonhee; Lee, Byung Kook; Jiang, Xiaohui; Wang, Yan

doi:10.1016/j.jconrel.2019.05.003

Cited by 298 publications

(204 citation statements)

References 37 publications

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“…Indeed, given the modular fabrication strategy, other synthetic and natural polymeric materials can be used for realizing DPNs, including polycaprolactone, chitosan, hyaluronic acid, and a variety of block-copolymers. PLGA and PEG were selected for their wellknown biodegradation and excretion profiles, even in human subjects (Bobo et al, 2016;Park et al, 2019). The geometrical and mechanical configurations of DPNs have been selected to enhance lodging within the malignant tissue by taking advantage of the high vascular tortuosity and low perfusion of tumor capillaries.…”

Section: Introductionmentioning

confidence: 99%

Optimizing the Pharmacological Properties of Discoidal Polymeric Nanoconstructs Against Triple-Negative Breast Cancer Cells

Ferreira

Rizzuti

Palange

et al. 2020

Front. Bioeng. Biotechnol.

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Fine-tuning loading and release of therapeutic and imaging agents associated with polymeric matrices is a fundamental step in the preclinical development of novel nanomedicines. Here, 1,000 × 400 nm Discoidal Polymeric Nanoconstructs (DPNs) were realized via a top-down, template-based fabrication approach, mixing together poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol)-diacrylate (PEG-DA) chains in a single polymer paste. Two different loading strategies were tested, namely the "direct loading" and the "absorption loading." In the first case, the agent was directly mixed with the polymeric paste to realize DPNs whereas, in the second case, DPNs were first lyophilized and then rehydrated upon exposure to a concentrated aqueous solution of the agent. Under these two loading conditions, the encapsulation efficiencies and release profiles of different agents were systematically assessed. Specifically, six agents were realized by conjugating lipid chains (DSPE) or polymeric chains (PEG) to the near-infrared imaging molecule Cy5 (DSPE-Cy5 A and DSPE-Cy5 B); the chemotherapeutic molecules methotrexate (DSPE-MTX and PEG-MTX) and doxorubicin (LA-DOX and DSPE-DOX). Moderately hydrophobic compounds with low molecular weights (MW) returned encapsulation efficiencies as high as 80% for the absorption loading. In general, direct loading was associated with encapsulation efficiencies lower than 1%. The agent hydrophobicity and MW were shown to be critical also in tailoring the release profiles from DPNs. On triple-negative breast cancer cells (MDA-MB-231), absorption loaded DOX-DPNs showed cytotoxic activities comparable to free DOX but slightly delayed in time. Preliminary in vivo studies demonstrated the high stability of Cy5-DPNs. Collectively, these results demonstrate that the pharmacological properties of DPNs can be finely optimized by changing the loading strategies (direct vs. absorption) and compound attributes (hydrophobicity and molecular weight).

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Section: Introductionmentioning

confidence: 99%

Optimizing the Pharmacological Properties of Discoidal Polymeric Nanoconstructs Against Triple-Negative Breast Cancer Cells

Ferreira

Rizzuti

Palange

et al. 2020

Front. Bioeng. Biotechnol.

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“…Vanoxerine is a potent and selective dopamine reuptake inhibitor (DRI). Vanoxerine binds to the target site on the dopamine transporter (DAT) ~50 times more strongly than cocaine but simultaneously inhibits the release of dopamine [21]. This combined effect only slightly elevates dopamine levels and block the rewarding effects of cocaine.…”

Section: Introductionmentioning

confidence: 99%

A Multicenter, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Long-Acting Injectable Formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) for Cocaine Relapse Prevention

Kadric¹,

Möhler²,

Kallioniemi³

et al. 2019

WJNS

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“…These results indicate that, for these polymers under the conditions used, the difference in solvation is unlikely to be a driving factor in the difference between measured M n by NMR and GPC. It is worth noting that, for long‐chain PLGAs, drastic differences between results obtained by GPC–4D and GPC–ES were observed . It is possible that the PEG–block itself interferes with the solvation of PLGA, altering the hydrodynamic radius, and this effect may be relatively small for molecular weight block copolymers.…”

Section: Discussionmentioning

confidence: 97%

Narrow molecular weight margins for the thermogelling property of polyester–polyether block copolymers in aqueous solutions

Garner

Hadar

Skidmore

et al. 2019

J of Applied Polymer Sci

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Polyester–polyether block copolymers with thermogelling properties have been widely used in pharmaceutical and biomedical applications for their biocompatibility and degradation to nontoxic components. The biodegradable polymers, such as poly(lactide‐co‐glycolide) and poly(lactide‐co‐caprolactone) (PLCL), have been used as the polyester block. The most commonly used polyether has been poly(ethylene glycol) (PEG). The thermogelling polymers dissolve in cold water, but become a semisolid gel at higher temperatures, for example, body temperature. This thermogelling property, however, occurs only within very narrow molecular weight ranges of the polyester at given polyether blocks. Only a few hundred Dalton differences in the polyester block can turn a thermogelling polymer into a water‐insoluble polymer. This study describes the hydrophilic and hydrophobic block sizes for endowing the thermogelling property and a simple, water‐free, synthesis of new thermogelling PLCL–PEG–PLCL triblock polymers. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020, 137, 48673.

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Injectable, long-acting PLGA formulations: Analyzing PLGA and understanding microparticle formation

Cited by 298 publications

References 37 publications

Optimizing the Pharmacological Properties of Discoidal Polymeric Nanoconstructs Against Triple-Negative Breast Cancer Cells

Optimizing the Pharmacological Properties of Discoidal Polymeric Nanoconstructs Against Triple-Negative Breast Cancer Cells

A Multicenter, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Long-Acting Injectable Formulation of Vanoxerine (Vanoxerine Consta 394.2 mg) for Cocaine Relapse Prevention

Narrow molecular weight margins for the thermogelling property of polyester–polyether block copolymers in aqueous solutions

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