Long-acting delivery systems for peptides: inhibition of rat prostate tumors by controlled release of [D-Trp6]luteinizing hormone-releasing hormone from injectable microcapsules.

Redding, Tommie W.; Schally, Andrew V.; Tice, Thomas R.; Meyers, William E.

doi:10.1073/pnas.81.18.5845

Cited by 132 publications

(95 citation statements)

References 22 publications

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“…Consequently, we started the development of such a long-acting delivery system for RC-160 by using a formulation in microcapsules of poly(DL-lactide-coglycolide) similar to that successfully employed for [D-Trp6]LH-RH (7,8). This polymer is biodegradable and biocompatible with living tissue.…”

mentioning

confidence: 99%

Radioimmunoassay for octapeptide analogs of somatostatin: measurement of serum levels after administration of long-acting microcapsule formulations.

Mason-Garcia

Vaccarella

Horváth

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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The development of a long-acting delivery system for D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160), an octapeptide analog of somatostatin, required the establishment of a method for determining the concentration of this analog in serum during treatment. A sensitive and specific radioimmunoassay (RIA) for RC-160 was developed and used for following the rate of liberation of this peptide from microcapsules of poly(DL-lactide-coglycolide). Antibodies were generated in a rabbit against RC-160 coinugated to bovine serum albumin with glutaraldehyde. At an antiserum dilution of 1:100,000, the antibodies bound approximately 25% of added radiolabeled RC-160. Somatostatin octapeptide analogs that had a disulfide bridge showed crossreactivity with the antiserum, but analogs without the disulfide bridge and other peptides tested did not crossreact. The minimum detectable dose of RC-160 was 10 pg. Intra-and interassay coefficients of variation ranged from 9.1% to 12.8% and from 14% to 30%, respectively. The RIA was suitable for direct determination of RC-160 in serum. Eleven prototype batches of microcapsules were tested in rats, and the rate of release of the analog from the microcapsules was followed. An improved batch of microcapsules made from RC-160 pamoate maintained high serum levels of RC-160 for more than 30 days after intramuscular injection. The RIA should be of value for monitoring levels of this analog in serum during long-term therapy.Superactive analogs of somatostatin such as D-Phe-CTs-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) and D-Phe-Cs-TyTrLys-Val-C's-Thr-NH2 (RC-121) show a high potency and a long duration of action in tests for inhibition of growth hormone release and much lower activity for suppression of insulin, glucagon, and gastric acid secretion (1, 2). This indicates a marked selectivity in their biological actions, which could make them useful for the treatment of endocrinerelated diseases such as type I diabetes mellitus and diabetic retinopathy.There is also experimental evidence that somatostatin analogs might be used to treat pancreatic cancer (3) by inhibiting the release of gastrointestinal hormones such as secretin, gastrin, and cholecystokinin or by stimulating the dephosphorylation of membrane receptors for the epidermal growth factor (4). In addition, somatostatin analogs of this class inhibit the growth of experimental prostate and mammary tumors by suppressing the levels of prolactin, growth hormone, and insulin-like growth factor I (IGF-I, somatomedin C) (5) and could be used as adjuncts to therapy with analogs of luteinizing hormone-releasing hormone (LH-RH).Thus, therapeutic application of these analogs in the treatment of various hormone-sensitive tumors is likely (6).The use of RC-160 and related analogs for the therapy of hormone-dependent tumors and endocrine disorders would be greatly enhanced by delayed delivery systems capable of maintaining controlled levels of the peptide over an extended period of time. Consequently, we started the development of such a long-acti...

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mentioning

confidence: 99%

Radioimmunoassay for octapeptide analogs of somatostatin: measurement of serum levels after administration of long-acting microcapsule formulations.

Mason-Garcia

Vaccarella

Horváth

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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“…The ratio of these two monomers used for polymerization and the average molecular weight of the resulting polymer determine the kinetics of release of the drug from PLGA microparticles [8][9][10][11] or from the drug-PLGA mixture in in situ implant form.…”

Section: -7)mentioning

confidence: 99%

“…[5][6][7] Poly(lactic-co-glycolic acid) (PLGA) is prepared by random copolymerization of lactic acid and glycolic acid, with the two different monomers being connected by ester linkages. The ratio of these two monomers used for polymerization and the average molecular weight of the resulting polymer determine the kinetics of release of the drug from PLGA microparticles [8][9][10][11] or from the drug-PLGA mixture in in situ implant form. 12) An example of the utilization of these properties of PLGA microparticles is Leuplin (Takeda Pharmaceutical Co., Ltd., Osaka, Japan), a PLGA particle formulation composed of poly-lactic acid microcapsules with a diameter in the order of micrometers and encapsulating a derivative of luteinizing-hormone releasing hormone.…”

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confidence: 99%

Evaluating the Properties of Poly(lactic-<i>co</i>-glycolic acid) Nanoparticle Formulations Encapsulating a Hydrophobic Drug by Using the Quality by Design Approach

Kozaki

Kobayashi

Goda³

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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We applied the Quality by Design (QbD) approach to the development of poly(lactic-co-glycolic acid) (PLGA) nanoparticle formulations encapsulating triamcinolone acetonide, and the critical process parameters (CPPs) were identified to clarify the correlations between critical quality attributes and CPPs. Quality risk management was performed by using an Ishikawa diagram and experiments with a fractional factorial design (ANOVA). The CPPs for particle size were PLGA concentration and rotation speed, and the CPP for relative drug loading efficiency was the poor solvent to good solvent volume ratio. By assessing the mutually related factors in the form of ratios, many factors could be efficiently considered in the risk assessment. We found a two-factor interaction between rotation speed and rate of addition of good solvent by using a fractional factorial design with resolution V. The system was then extended by using a central composite design, and the results obtained were visualized by using the response surface method to construct a design space. Our research represents a case study of the application of the QbD approach to pharmaceutical development, including formulation screening, by taking actual production factors into consideration. Our findings support the feasibility of using a similar approach to nanoparticle formulations under development. We could establish an efficient method of analyzing the CPPs of PLGA nanoparticles by using a QbD approach.Key words Quality by Design (QbD); critical quality attribute; critical process parameter; poly(lactic-coglycolic acid) (PLGA); nanoparticle formulation The use of Quality by Design (QbD), an approach aimed at scientific and systematic pharmaceutical development to ensure quality throughout the life cycles of pharmaceutical products, has recently been recommended.2-4) Construction of such a control strategy in the future is also desirable for nanoparticle formulations as representative functional dosage forms. However, attempts to construct QbD-based quality-control strategies for nanoparticle formulations can be difficult, because the pharmaceutical properties and manufacturing processes required are more complex than are those for conventional pharmaceutical products. In addition, the approaches designed for establishing QbD-based quality management strategies may vary markedly depending on the product types of nanoparticle formulations. Accordingly, few examples of the application of the QbD approach to nanoparticle formulations are available currently. 5-7)Poly(lactic-co-glycolic acid) (PLGA) is prepared by random copolymerization of lactic acid and glycolic acid, with the two different monomers being connected by ester linkages. The ratio of these two monomers used for polymerization and the average molecular weight of the resulting polymer determine the kinetics of release of the drug from PLGA microparticles [8][9][10][11] or from the drug-PLGA mixture in in situ implant form.12) An example of the utilization of these properties of PLGA microparticles is L...

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“…The application of microencapsulated LH-RH analog in rats has been described (Redding et al, 1984;Mason-Garcia et al, 1985). The release of LH-RH analog from microcapsules can last for at least 1 month in rats (Mason-Garcia et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

A microencapsulated analog of LH-RH accelerates maturation but without stimulating sex reversal in the protandrous black porgy, Acanthopagrus schlegeli

Chang¹,

Yueh²,

Lee³

et al. 1995

Reprod. Nutr. Dev.

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Summary ― The objective of this study was to regulate the reproduction and levels of gonadal steroids in 3-year-old protandrous black porgy (Acanthopagrus schlegeli) by treatment with microencapsulated o-Trp s -luteinizing hormone-releasing hormone (LH-RH analog) during the prespawning season. Twenty-four previously male black porgy were equally divided into 2 groups and injected with vehicle (control group) or with microencapsulated LH-RH analog (LH-RH analog group), respectively. Spermiation and plasma levels of testosterone (T), estradiol-1 7p (E2) and 17a-hydroxyprogesterone (17a-OH P) were measured, after treatment, at intervals of 1-2 weeks for 4 months. Oocyte diameters were also measured after 4, 10, 12, 14 and 16 weeks of treatment. The microencapsulated LH-RH analog accelerated the onset of spermiation by at least 5 weeks. Oocyte diameters were also significantly increased in the LH-RH analog group. The microencapsulated LH-RH analog did not increase the number of sex-reversing females compared with the number in the control group. High levels of plasma E2 were found in the sex-reversing females in the LH-RH analog and control groups during the prespawning and spawning season. Low levels of plasma E2 were observed in the non-reversed males in both the LH-RH analog and the control groups. Similar profiles of plasma T levels were detected in male and in reversing female black porgy in the LH-RH analog and control groups. Plasma 17a-OH P levels were low and constant throughout the experimental period in fish in each group. These findings indicate that the microencapsulated LH-RH analog accelerated gonadal maturation in the black porgy during the prespawning season. Plasma levels of E2 seem to be closely related to the occurrence of natural sex reversal in the protandrous black porgy, A schlegeli.

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Long-acting delivery systems for peptides: inhibition of rat prostate tumors by controlled release of [D-Trp6]luteinizing hormone-releasing hormone from injectable microcapsules.

Cited by 132 publications

References 22 publications

Radioimmunoassay for octapeptide analogs of somatostatin: measurement of serum levels after administration of long-acting microcapsule formulations.

Radioimmunoassay for octapeptide analogs of somatostatin: measurement of serum levels after administration of long-acting microcapsule formulations.

Evaluating the Properties of Poly(lactic-<i>co</i>-glycolic acid) Nanoparticle Formulations Encapsulating a Hydrophobic Drug by Using the Quality by Design Approach

A microencapsulated analog of LH-RH accelerates maturation but without stimulating sex reversal in the protandrous black porgy, Acanthopagrus schlegeli

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