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Preparation of TPP-crosslinked chitosan microparticles by spray drying for the controlled delivery of progesterone intended for estrus synchronization in cattle

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Abstract

Purpose

Planned reproduction in cattle involves regulation of estrous cycle and the use of artificial insemination. Cycle control includes the administration of exogenous progesterone during 5–8 days in a controlled manner allowing females to synchronize their ovulation. Several progesterone delivery systems are commercially available but they have several drawbacks. The aim of the present contribution was to evaluate chitosan microparticles entrapping progesterone as an alternative system.

Methods

Microparticles were prepared by spray drying. The effect of formulation parameters and experimental conditions on particle features and delivery was studied. A mathematical model to predict progesterone plasma concentration in animals was developed and validated with experimental data.

Results

Microparticle size was not affected by formulation parameters but sphericity enhances as Tween 80 content increases and it impairs as TPP content rises. Z potential decreases as phosphate content rises. Particles remain stable in acidic solution but the addition of surfactant is required to stabilize dispersions in neutral medium. Encapsulation efficiencies was 69–75%. In vitro delivery studies showed burst and diffusion-controlled phases, being progesterone released faster at low pH. In addition, delivery extend in cows was affected mainly by particle size and hormone initial content, while the amount injected altered plasma concentration. Theoretical predictions with excellent accuracy were obtained.

Conclusion

The mathematical model developed can help to find proper particle features to reach specific delivery rates in the animals. This not only save time, money and effort but also minimized experimentation with animals which is desired from an ethical point of view.

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Abbreviations

DD:

Deacetylation degree (DD)

DSC:

Differential Scanning Calorimetry

EEf:

Encapsulation efficiency

FT-IR:

Fourier Transform Infrared Spectroscopy

HPLC:

High Performance Liquid Chromatography

SEM:

Scanning Electron Microscopy

TPP:

Tripolyphosphate

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ACKNOWLEDGMENTS AND DISCLOSURES

uthors wish to express their gratitude to Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) and to Universidad Nacional del Litoral (UNL) of Argentina for the financial support granted to this contribution.

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Authors and Affiliations

  1. Instituto de Desarrollo Tecnológico para la Industria Química (INTEC Universidad Nacional del Litoral and CONICET), Güemes 3450, 3000, Santa Fe, Argentina

    Ignacio M. Helbling, Carlos A. Busatto, Juan I. Pesoa, Diana A. Estenoz & Julio A. Luna

  2. Instituto de Tecnología de Alimentos (ITA, Facultad de Ingeniería Química - Universidad Nacional del Litoral), Santiago del Estero 2829, 3000, Santa Fe, Argentina

    Silvana A. Fioramonti & Liliana Santiago

Authors
  1. Ignacio M. Helbling
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  2. Carlos A. Busatto
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  3. Silvana A. Fioramonti
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  4. Juan I. Pesoa
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  5. Liliana Santiago
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  6. Diana A. Estenoz
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  7. Julio A. Luna
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Correspondence to Ignacio M. Helbling.

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Helbling, I.M., Busatto, C.A., Fioramonti, S.A. et al. Preparation of TPP-crosslinked chitosan microparticles by spray drying for the controlled delivery of progesterone intended for estrus synchronization in cattle. Pharm Res 35, 66 (2018). https://doi.org/10.1007/s11095-018-2363-z

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  • DOI: https://doi.org/10.1007/s11095-018-2363-z

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