Aging is characterized by decreased collagen production. Collagen peptide is a hydrolyzed product of collagen. The topical peptide collagen could act as anti-aging, however, only a small concentration of peptide collagen could penetrate the skin. A microsphere is a micro-spherical particle that could increase the penetration of molecules via a transcellular pathway. This present study aims to optimize the microsphere formation of various collagen peptides as active agents, using alginate as a polymer and CaCl2 as a cross-linker. The microsphere was prepared with collagen peptide (CP), hydrolyzed collagen, CP with molecular weight (MW) < 30 kDa and CP with MW > 30 kDa. The microsphere was then characterized for its size, flowability, topography (SEM), protein-alginate interaction (ATRFTIR and DSC), drug loading, and entrapment efficiency. The molecular size of collagen peptide influences the microsphere characteristic. The higher molecular size of collagen resulted in higher microsphere size. The microsphere of CP with MW < 30 kDa has an average size of 2.25 µm (compared to native collagen with an average size of 5.00 µm). The moisture content of the microsphere is 2.27 to 3.52%. The highest drug loading was observed in the native collagen microsphere (23.85%), while the highest entrapment efficiency was also found in the native collagen microsphere (61.80%). From the SEM analysis, all the microspheres showed a sphere's shape. The fingerprint area of protein and alginate was detected in all formulations. Our study showed that the different size of collagen significantly influences the microsphere characteristics.
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