Characterization of a polymeric PLGA-injectable implant delivery system for the controlled release of proteins

Eliaz, Rom E.; Kost, Joseph

doi:10.1002/(sici)1097-4636(20000605)50:3<388::aid-jbm13>3.3.co;2-6

Cited by 41 publications

(69 citation statements)

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“…The dark ground optical system has been invaluable in evaluating the underlying mechanisms involved in the phase inversion process, but is limited to thin films and can only be used for a short time scale relative to the life of the implant [15–18]. Another common technique for imaging in situ forming implants is scanning electron microscopy [3, 16, 17, 20, 22, 23]. One shortcoming of this technique is that the implants are destroyed in the process, since sample preparation most often involves freezing and sectioning of the implants.…”

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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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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“…Biodegradable, biocompatible, phase sensitive, and thermosensitive smart polymer based drug delivery systems offer several advantages such as they release the drug in a predefined controlled manner, can be used for hydrophilic and hydrophobic or small and large molecular weight therapeutic agents, low burst release, low batch‐to‐batch variation in comparison to implants or microspheres, achieve high drug loading (up to 90%) in comparison to microspheres, and ease of preparation. The injectable biodegradable phase sensitive delivery system utilizes a miscible blend of a water insoluble polymer and a water miscible biocompatible solvent such as N ‐methyl‐2‐pyrrolidone (NMP), dimethyl sulfoxide (DMSO), glycofurol, triacetin, ethyl benzoate, and benzyl benzoate 10–14. Upon injection into an aqueous tissue environment, the water soluble solvent diffuses out of the polymer, which then precipitates, resulting in a solid implant in vivo , from which the drug is released in a controlled fashion 15.…”

Section: Introductionmentioning

confidence: 99%

In Vivo Absorption of Steroidal Hormones from Smart Polymer Based Delivery Systems

Chen

Pederson

Oak

et al. 2010

Journal of Pharmaceutical Sciences

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The purpose of this study was to develop smart polymer based controlled delivery systems to deliver steroidal hormones after single subcutaneous injection at predetermined rates over extended period of time. In vivo absorption and pharmacokinetics of levonorgestrel and testosterone were investigated from the thermosensitive and phase sensitive polymeric controlled delivery systems. A selective, reliable and rapid method for determination of serum levonorgestrel concentration was developed using High Performance Liquid Chromatography - Tandom Mass Spectrometry with Atmospheric Pressure Chemical Ionization Interface, while testosterone in serum samples was detected and quantified by a competitive immunoassay. The delivery systems controlled the absorption of levonorgestrel in rabbits up to 6 weeks from thermosensitive and ~4 weeks from phase sensitive polymeric delivery systems. In vivo study of testosterone delivery systems in castrated rabbits controlled the release of testosterone for at least 2 months from both thermosensitive and phase sensitive polymers. Thermosensitive and phase sensitive polymer formulations significantly (p<0.05) increased relative bioavailability of steroidal hormones compared to control. In conclusion, thermosensitive and phase sensitive polymer based delivery systems controlled the release in vivo in rabbits for longer duration after single subcutaneous injection.

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“…The most employed solvents are those with high miscibility with water like N‐methyl‐2‐pyrrolidone (NMP), dimethyl sulfoxide (DMSO), propylene glycol, acetone, tetrahydrofuran, 2‐pyrrolidone, ethyl acetate, glycofurol[5] or low molecular weight polyethylene glycol [6]. Among them, NMP is the most used because of its solvating ability and its low systemic toxicity when employed for the preparation of in‐situ forming implants [7]…”

Section: Introductionmentioning

confidence: 99%

In-situ forming gel-like depot of a polyaspartamide-polylactide copolymer for once a week administration of sulpiride

Fiorica

Palumbo

Pitarresi

et al. 2015

Journal of Pharmacy and Pharmacology

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Characterization of a polymeric PLGA-injectable implant delivery system for the controlled release of proteins

Cited by 41 publications

References 0 publications

Noninvasive characterization of in situ forming implants using diagnostic ultrasound

Noninvasive characterization of in situ forming implants using diagnostic ultrasound

In Vivo Absorption of Steroidal Hormones from Smart Polymer Based Delivery Systems

In-situ forming gel-like depot of a polyaspartamide-polylactide copolymer for once a week administration of sulpiride

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