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Development and Characterization of Saturated Fatty Acid-Engineered, Silica-Coated Lipid Vesicular System for Effective Oral Delivery of Alfa-Choriogonadotropin

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Abstract

The present study was designed to develop an efficient, safe, and patient-friendly dosage form, for oral delivery of alfa-choriogonadotropin, used in the treatment of female reproductive infertility. Silica-coated, saturated fatty acid (dipalmitoylphosphatidylcholine (DPPC))-engineered, nanolipidic vesicular (NLVs) system was developed for systemic delivery of therapeutic peptide, alfa-choriogonadotropin, through oral route. DPPC-based NLVs were formulated using the technique of thin-film hydration and were coated with silica to form a homogeneous surface silica shell. The formulated silica-coated NLVs were evaluated for physicochemical and physiologic stability under simulated conditions and were optimized based on physicochemical parameters like particle size, zeta potential, polydispersity index (PDI), entrapment efficiency, and in vitro release profile. Silica-coated, DPPC-based NLVs imparted physicochemical stability to entrapped alfa-choriogonadotropin against the biological environment prevailing in the human gastrointestinal tract (GIT). In vivo, subchronic animal toxicity studies were performed to assess the safety of the designed dosage form. Results of in vitro characterization and in vivo pharmacokinetic studies of fabricated formulation revealed that the silica-coated, DPPC-based NLV formulation was not only stable in human GIT but was also as efficacious as a marketed parenteral formulation for the systemic delivery of alfa-choriogonadotropin. In vivo toxicity studies revealed that silica-coated NLVs did not alter hematological and serum biochemical parameters. The histopathological studies also depicted no macroscopic changes in major organs; thus, the developed formulation was proven to be nontoxic and equally efficient as a marketed parenteral formulation for the delivery of alfa-choriogonadotropin with added benefits of possible self-medication, more patient acceptability, and no chances of infection.

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Abbreviations

DPPC:

Dipalmitoylphosphatidylcholine

NLVs:

Nanolipidic vesicles

GIT:

Gastrointestinal tract

PDI:

Polydispersity index

DLS:

Dynamic light scattering

ELS:

Electrophoretic light scattering

TEM:

Transmission electron microscopy

SEM:

Scanning electron microscopy

RBC:

Red blood cell count

HBG:

Hemoglobin concentration

PLT:

Platelet count

MCV:

Mean corpuscular volume

WBC:

Total white blood cells

DLC:

Differential leukocyte count

MON:

Monocytes

NEU:

Neutrophils

LYM:

Lymphocytes

GPT:

Glutamic pyruvic transaminase

GOT:

Serum glutamic oxaloacetic transaminase

CRE:

Creatinine

PRO:

Total protein

ALB:

Albumin

CHO:

Cholesterol

TRIG:

Triglycerides

GLU:

Glucose

ALP:

Alkaline phosphate

LHCG:

Luteinizing hormone/choriogonadotropin receptors

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Acknowledgements

The authors of the current research findings are thankful to LIPOID, Germany, for generously providing the gift samples of saturated lipid (DPPC), used in the engineering of the presented drug delivery technology.

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Authors and Affiliations

  1. Department of Pharmaceutics, B.V. Patel Pharmaceutical Education and Research Development Centre, Ahmedabad, Gujarat, 380054, India

    Viral Shah

  2. Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Ahmedabad, Gujarat, India

    Amee Jobanputra

  3. Department of Pharmacology, Institute of Pharmacy, Nirma University, S.G. Highway, Ahmedabad, Gujarat, India

    Bhagawati Saxena

  4. Department of Pharmacology, B.V. Patel Pharmaceutical Education and Research Development Centre, Ahmedabad, Gujarat, India

    Manish Nivsarkar

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  1. Viral Shah
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Correspondence to Viral Shah.

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Shah, V., Jobanputra, A., Saxena, B. et al. Development and Characterization of Saturated Fatty Acid-Engineered, Silica-Coated Lipid Vesicular System for Effective Oral Delivery of Alfa-Choriogonadotropin. AAPS PharmSciTech 22, 118 (2021). https://doi.org/10.1208/s12249-021-01985-0

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