Biocompatibility of an Injectable In Situ Forming Depot for Peptide Delivery

Schoenhammer, Karin; Boisclair, Julie; Schuetz, Helmut; Petersen, Holger; Goepferich, Achim

doi:10.1002/jps.22149

Cited by 19 publications

(10 citation statements)

References 25 publications

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“…In situ depot-forming (ISDF) systems, implant systems, and crystallization are other means of parenteral delivery techniques [104]. Schoenhammer et al (2010) used ISFD containing poly(D,L-lactide-co-glycolide) (PLGA) to prepare a sustained release formulation of pasireotide, a cyclohexapeptide somatostatin analogue engineered to bind to multiple somatostatin receptor subtypes currently in phase III development for treatment of acromegaly, and then evaluated its functionality using in vitro and in vivo tests [108].…”

Section: Peptide and Protein Delivery Technologiesmentioning

confidence: 99%

Phage display as a technology delivering on the promise of peptide drug discovery

Hamzeh‐Mivehroud

Alizadeh

Morris

et al. 2013

Drug Discovery Today

142

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Section: Peptide and Protein Delivery Technologiesmentioning

confidence: 99%

Phage display as a technology delivering on the promise of peptide drug discovery

Hamzeh‐Mivehroud

Alizadeh

Morris

et al. 2013

Drug Discovery Today

142

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“…Recently, PEG-alkyl ether and glycofurol have been investigated for PLGA implants. Both solvents have been indicated to be well tolerated and biocompatible in vivo 25-27 . Glycofurol has been shown to be compatible with PLGA polymer causing minimal polymer degradation.…”

Section: In Situ Injectable Gel/implantsmentioning

confidence: 99%

Long-term delivery of protein therapeutics

Vaishya

Khurana

Patel

et al. 2014

Expert Opinion on Drug Delivery

167

104

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Introduction Proteins are effective biotherapetics with applications in diverse ailments. Despite being specific and potent, their full clinical potential has not yet been realized. This can be attributed to short half-lives, complex structures, poor in vivo stability, low permeability frequent parenteral administrations and poor adherence to treatment in chronic diseases. A sustained release system, providing controlled release of proteins, may overcome many of these limitations. Areas covered This review focuses on recent development in approaches, especially polymer-based formulations, which can provide therapeutic levels of proteins over extended periods. Advances in particulate, gel based formulations and novel approaches for extended protein delivery are discussed. Emphasis is placed on dosage form, method of preparation, mechanism of release and stability of biotherapeutics. Expert opinion Substantial advancements have been made in the field of extended protein delivery via various polymer-based formulations over last decade despite the unique delivery-related challenges posed by protein biologics. A number of injectable sustained-release formulations have reached market. However, therapeutic application of proteins is still hampered by delivery related issues. A large number of protein molecules are under clinical trials and hence there is an urgent need to develop new methods to deliver these highly potent biologics.

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“…Several methods have been used to determine plasma levels of octreotide, pasireotide, or lanreotide, SSAs that are structurally similar to AP102, mostly using highly sensitive radioimmunoassay with sensitivities of 78 pg/mL or 1 pg/sample. [10][11][12][13][14] However, the results obtained by these methods may be overestimated because of potential antibody cross-reactivity. Conversely, liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods provide a higher specificity but often a lower sensitivity.…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12][13][14] However, the results obtained by these methods may be overestimated because of potential antibody cross-reactivity. [10][11][12][13][14] However, the results obtained by these methods may be overestimated because of potential antibody cross-reactivity.…”

mentioning

confidence: 99%

Sensitive quantification of the somatostatin analog AP102 in plasma by ultra‐high pressure liquid chromatography–tandem mass spectrometry and application to a pharmacokinetic study in rats

Eugster¹,

Boyle

Prod’hom³

et al. 2018

Drug Testing and Analysis

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AP102 is a di-iodinated octapeptide somatostatin agonist (SSA) designed to treat acromegaly and neuroendocrine tumors. A sensitive and selective method was validated for the quantification of AP102 in plasma following the European Medicines Agency (EMA) and Food and Drug Administration (FDA) guidelines. Sample preparation was performed using solid-phase extraction microplates. Chromatographic separation was achieved on an ultra-high pressure liquid chromatography (UHPLC) C18 column in 6.0 minutes. The compounds were quantified using multiple reaction monitoring on a tandem quadrupole mass spectrometer with C, N-labeled AP102 as internal standard. Calibration ranged from 50 to 10000 pg/mL. The lower limit of quantification (LLOQ) was measured at 20 pg/mL, and robust analytical performances were obtained with trueness at 99.2%-100.0%, intra-assay imprecision at 2.5%-4.4%, and inter-assay imprecision at 8.9%-9.7%. The accuracy profiles (total error) built on the 3 concentrations levels showed accuracy within the 70%-130% range. AP102 is remarkably stable since no proteolytic fragments were detected on plasma samples analyzed by Orbitrap-MS. Pharmacokinetic studies were conducted in rats, after single dose (1, 3, and 10 μg/kg, sc) and continuous subcutaneous administration (osmotic minipumps for 28 days, 3.0 or 10.0 μg/kg/h). AP102 showed a rapid absorption by the subcutaneous route (T : 15-30 minutes) and a fast elimination (t : 33-86 minutes). The PK profile of AP102 exhibited a mean clearance of 1.67 L/h and a mean distribution volume at steady state of 7.16 L/kg, about 10-fold higher than those observed with other SSA or non- and mono-iodinated AP102. LogD determination confirmed the lipophilic properties of AP102 that might influence its distribution in tissues.

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Biocompatibility of an Injectable In Situ Forming Depot for Peptide Delivery

Cited by 19 publications

References 25 publications

Phage display as a technology delivering on the promise of peptide drug discovery

Phage display as a technology delivering on the promise of peptide drug discovery

Long-term delivery of protein therapeutics

Sensitive quantification of the somatostatin analog AP102 in plasma by ultra‐high pressure liquid chromatography–tandem mass spectrometry and application to a pharmacokinetic study in rats

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