Properties of a Stable and Sustained-Release Formulation of Recombinant Human Parathyroid Hormone (rhPTH) with Chitosan and Silk Fibroin Microparticles

Abstract

BackgroundParathyroid hormone (PTH) is required for the maintenance of normal bone physiology. This study describes the properties of a sustained-release formulation of recombinant human PTH (rhPTH) using chitosan and silk fibroin microparticles as carriers for drug delivery, developed using a spray-drying method.Material/MethodsChitosan, silk fibroin, and chitosan/silk fibroin microparticles loaded with rhPTH were studied with scanning electron microscopy (SEM) to estimate the particle size and surface morphology. The in vitro release of rhPTH was used to assess the developed formulation. The effect of the spray-drying process was assessed by powder X-ray diffraction (PXRD) of the microparticles. Quantification of the released rhPTH was performed by enzyme-linked immune sorbent assay (ELISA). Fourier-transform infrared spectroscopy (FTIR) was used to determine the differences in the absorption frequency of samples.ResultsSurface morphology of the final formulation showed the absence of pure crystals of chitosan and silk fibroin in the final formulation and FTIR demonstrated electrostatic interactions between chitosan and silk fibroin, which was supported by PXRD. The chitosan/silk fibroin microparticles loaded with rhPTH showed an entrapment efficiency (EE) that ranged from 60.36–72.99% with a 50% rhPTH release profile at pH 7.5 in 24 hours. There was no particle aggregation in blood and little hemolysis, indicating stability of the rhPTH-loaded microparticles.ConclusionsA silk fibroin/chitosan microparticle formulation loaded with rhPTH was shown to be stable and to provide sustained-release of rhPTH, supporting a potential role of this formulation in the treatment of bone diseases including osteoporosis and bone fracture.

Oral delivery of protein and peptide drugs: from non-specific formulation approaches to intestinal cell targeting strategies

“…Surface modification of microparticles can be achieved by conjugation, coating or crosslinking. For example, collagen microparticles modified by photochemical crosslinking 62 , and silk fibroin coated polylactide-co-glycolide acid (PLGA) and alginate microparticles have been used to further prolong the release of the peptide drug 63 . Onishi et al have developed enteric-coated chitosan-4-thio-butylamidine conjugate microparticles for oral delivery of calcitonin 64 .…”

Chitosan/Silk Fibroin Materials for Biomedical Applications—A Review

“…Apart from the tests of mixtures of chitosan with silk fibroin in the form of diluted solutions, nanofibers [ 112 , 117 , 118 , 119 ], three-dimensional structures [ 101 , 108 , 109 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 ], films [ 103 , 105 , 110 , 114 , 130 , 131 , 132 , 133 ], microparticles [ 134 , 135 , 136 , 137 ], and hydrogels [ 138 , 139 , 140 ] were also obtained and characterized ( Figure 5 ).…”

Silk‐based microcarriers: current developments and future perspectives

“…Nevertheless, chitosan microparticles have limitations such as a high initial burst release rate and a short period of sustained‐release [88]. Several works focus on the synthesis of fibroin/chitosan to increase the release period, using a spray‐drying technique [62, 89] or an emulsification approach [90–92]. The microspheres obtained usually present a smooth [88, 90] or wrinkled surface [90–92] with a diameter that can range from ∼7 to 150 μm [90].…”