Enhanced protein delivery by multi-ion containing eggshell derived apatitic-alginate composite nanocarriers

Natural calcium sources like eggshells are being explored for biomedical applications due to their bioactive properties. While synthetic hydroxyapatite is widely used in bone tissue engineering, it lacks the ion diversity and degradability of natural bone minerals. Researchers have long sought to improve protein delivery systems by mimicking the composition of natural bone minerals. Prior studies have demonstrated that calcium-deficient hydroxyapatite (CDHA) offers better bioactivity and controlled release than stoichiometric HA. However, the impact of ion composition and nanoparticle structure on protein release remains unclear. This uncertainty drove the need to investigate eggshell-derived CDHA for its potential in protein delivery. No prior work had resolved how ion content from natural sources affects release profiles. The field lacks a comprehensive understanding of how natural mineral composition influences delivery efficiency. This gap motivated the current study to explore eggshell-derived CDHA as a novel nanocarrier.

The aim of this research was to develop a protein delivery system using eggshell-derived calcium-deficient hydroxyapatite (ECDHA) nanoparticles. The researchers focused on creating a material that mimics the natural composition of bone minerals. They aimed to determine how ion content from eggshells affects delivery efficiency. The specific problem addressed was the limited release of proteins from synthetic CDHA. The motivation was to improve controlled release for tissue engineering applications. The study sought to compare ECDHA with synthetic CDHA in terms of loading and release capacity. The researchers also aimed to evaluate the effect of alginate coating on release profiles. Their goal was to identify an optimal Ca/P ratio and coating strategy for enhanced delivery.

The study used microwave-accelerated wet chemical synthesis to produce ECDHA nanoparticles. Calcium precursors included both eggshells and synthetic calcium hydroxide. Different Ca/P molar ratios were tested to mimic bone mineral phases. Three Ca/P ratios (1.67, 1.61, 1.51) were selected to cover stable HA to degradable TCP. Bovine serum albumin (BSA) was used as a model protein to assess delivery profiles. Loading capacity was measured at each Ca/P ratio. Alginate coating was applied to selected nanoparticles to modify release behavior. Release profiles were evaluated over a two-day period to compare performance.

ECDHA nanoparticles achieved a maximum BSA loading of 57% at a Ca/P ratio of 1.51. Synthetic CDHA showed lower loading at 37% for the same ratio. ECDHA released 25% of BSA, compared to 6.5% from synthetic CDHA. Alginate-coated ECDHA achieved a 65% BSA release at a Ca/P ratio of 1.51. The highest release occurred within two days for coated samples. The Ca/P ratio of 1.51 was closest to degradable tricalcium phosphate (TCP). The combination of ECDHA and alginate coating improved release efficiency. These results suggest that ECDHA with a TCP-like composition and coating is optimal.

The authors propose that ECDHA nanoparticles with a Ca/P ratio similar to degradable TCP are ideal for protein delivery. Alginate coating significantly enhances BSA release compared to uncoated particles. The study suggests that ion diversity from eggshells contributes to better release profiles. The findings indicate that natural sources like eggshells may outperform synthetic materials. The researchers suggest that the combination of ECDHA and alginate coating is promising. The results support the use of ECDHA at a Ca/P ratio of 1.51 for optimal performance. The study does not claim that ECDHA is the only viable option, but it may be superior in this context. The authors propose that these findings could inform future work on bone tissue engineering.