Changes in morphology of in situ forming PLGA implant prepared by different polymer molecular weight and its effect on release behavior

Astaneh, Reyhaneh; Erfan, Mohammad; Moghimi, Hamidreza; Mobedi, Hamid

doi:10.1002/jps.21415

Cited by 74 publications

(52 citation statements)

References 29 publications

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“…This is crucial because it alters hydrophilicity, diffusion and degradation via non-enzymatic autocatalysis. Moreover it affects the viscosity of polymer solution and sol–gel phase inversion induced by precipitation following solvent removal, both of which have a bearing on release rates of encapsulated payload (8,9). It is therefore important to evaluate and define the influence of polymer MW on delivery of either single, or multiple TA.…”

Section: Introductionmentioning

confidence: 99%

Optimization of Stability, Encapsulation, Release, and Cross-Priming of Tumor Antigen-Containing PLGA Nanoparticles

et al. 2012

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Purpose In order to investigate Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP) as potential vehicles for efficient tumor antigen (TA) delivery to dendritic cells (DC), this study aimed to optimize encapsulation/release kinetics before determining immunogenicity of antigen-containing NP. Methods Various techniques were used to liberate TA from cell lines. Single (gp100) and multiple (B16-tumor lysate containing gp100) antigens were encapsulated within differing molecular weight PLGA co-polymers. Differences in morphology, encapsulation/release and biologic potency were studied. Findings were adopted to encapsulate fresh tumor lysate from patients with advanced tumors and compare stimulation of tumor infiltrating lymphocytes (TIL) against that achieved by soluble lysate. Results Four cycles of freeze-thaw + 15 s sonication resulted in antigen-rich lysates without the need for toxic detergents or protease inhibitors. The 80KDa polymer resulted in maximal release of payload and favorable production of immunostimulatory IL-2 and IFN-γ. NP-mediated antigen delivery led to increased IFN-γ and decreased immunoinhibitory IL-10 synthesis when compared to soluble lysate. Conclusions Four cycles of freeze-thaw followed by 15 s sonication is the ideal technique to obtain complex TA for encapsulation. The 80KDa polymer has the most promising combination of release kinetics and biologic potency. Encapsulated antigens are immunogenic and evoke favorable TIL-mediated anti-tumor responses.

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Section: Introductionmentioning

confidence: 99%

Optimization of Stability, Encapsulation, Release, and Cross-Priming of Tumor Antigen-Containing PLGA Nanoparticles

et al. 2012

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“…Typically the release profile has distinct regions of burst release, diffusion facilitated release, degradation facilitated release, and finally a period of drug depletion [11]. One of the greatest challenges in translating ISFI systems from the research phase to a clinical setting is the relatively large burst release [7].…”

Section: Introductionmentioning

confidence: 99%

Effect of injection site on in situ implant formation and drug release in vivo

Patel

Solorio

et al. 2010

Journal of Controlled Release

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In situ forming drug delivery implants offer an attractive alternative to pre-formed implant devices for local drug delivery due to their ability to deliver fragile drugs, simple manufacturing process, and less invasive placement. However, the clinical translation of these systems has been hampered, in part, by poor correlation between in vitro and in vivo drug release profiles. To better understand this effect, the behavior of poly(D,l-lactide-co-glycolide) (PLGA) in situ forming implants was examined in vitro and in vivo after subcutaneous injection as well as injection into necrotic, non-necrotic, and ablated tumor. Implant formation was quantified noninvasively using an ultrasound imaging technique. Drug release of a model drug agent, fluorescein, was correlated with phase inversion in different environments. Results demonstrated that burst drug release in vivo was greater than in vitro for all implant formulations. Drug release from implants in varying in vivo environments was fastest in ablated tumor followed by implants in non-necrotic tumor, in subcutaneous tissue, and finally in necrotic tumor tissue with 50% of the loading drug mass released in 0.7, 0.9, 9.7, and 12.7 h respectively. Implants in stiffer ablated and non-necrotic tumor tissue showed much faster drug release than implants in more compliant subcutaneous and necrotic tumor environments. Finally, implant formation examined using ultrasound confirmed that in vivo the process of precipitation (phase inversion) was directly proportional to drug release. These findings suggest that not only is drug release dependent on implant formation but that external environmental effects, such as tissue mechanical properties, may explain the differences seen between in vivo and in vitro drug release from in situ forming implants.

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“…These implants have a distinct release pattern consisting of a period of burst release followed by a period of diffusion facilitated release. As the matrix begins to degrade, the release is enhanced until the entire cache of drug has finally been depleted [20]. It has been shown that the drug release from PLGA is directly related to the rate of phase inversion, and that the burst release may be directly correlated to the rate of phase inversion and the resultant morphology of the polymer phase.…”

Section: Introductionmentioning

confidence: 99%

Noninvasive characterization of in situ forming implants using diagnostic ultrasound

Solorio

Babin

Patel

et al. 2010

Journal of Controlled Release

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In situ forming drug delivery systems provide a means by which a controlled release depot can be physically inserted into a target site without the use of surgery. The release rate of drugs from these systems is often related to the rate of implant formation. Currently, only a limited number of techniques are available to monitor phase inversion, and none of these methods can be used to visualize the process directly and noninvasively. In this study, diagnostic ultrasound was used to visualize and quantify the process of implant formation in a phase inversion based system both in vitro and in vivo. Concurrently, sodium fluorescein was used as a mock drug to evaluate the drug release profiles and correlate drug release and implant formation processes. Implants comprised of three different molecular weight poly(lactic-co-glycolic acid) (PLGA) polymers dissolved in 1-methyl-2-pyrrolidinone (NMP) were studied in vitro and a 29 kDa PLGA solution was evaluated in vivo. The implants were encapsulated in a 1% agarose tissue phantom for five days, or injected into a rat subcutaneously and evaluated for 48 hrs. Quantitative measurements of the gray-scale value (corresponding to the rate of implant formation), swelling, and precipitation were evaluated using Correspondence to: Agata A. Exner, agata.exner@case.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

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Changes in morphology of in situ forming PLGA implant prepared by different polymer molecular weight and its effect on release behavior

Cited by 74 publications

References 29 publications

Optimization of Stability, Encapsulation, Release, and Cross-Priming of Tumor Antigen-Containing PLGA Nanoparticles

Optimization of Stability, Encapsulation, Release, and Cross-Priming of Tumor Antigen-Containing PLGA Nanoparticles

Effect of injection site on in situ implant formation and drug release in vivo

Noninvasive characterization of in situ forming implants using diagnostic ultrasound

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