Stability and release mechanism of double emulsification (W1/O/W2) for biodegradable pH-responsive polyhydroxybutyrate/cellulose acetate phthalate microbeads loaded with the water-soluble bioactive compound niacinamide.

Microbeads of biodegradable polyhydroxybutyrate (PHB) offer environmental benefits and economic competitiveness. The aim of this study was to encapsulate a water-soluble bioactive compound, niacinamide (NIA), in a pH-responsive natural matrix composed of PHB and cellulose acetate phthalate (CAP) by double emulsification (W1/O/W2) to improve the encapsulation efficiency (%EE) and loading capacity (%LC). PHB was produced in-house by Escherichia coli JM109 pUC19-23119phaCABA-04 without the inducing agent isopropyl ß-D-1-thiogalactopyranoside (IPTG). The influences of PHB and polyvinyl alcohol (PVA) concentrations, stirring rate, PHB/CAP ratio and initial NIA concentration on the properties of NIA-loaded pH-responsive microbeads were studied. The NIA-loaded pH-responsive PHB/CAP microbeads exhibited a spherical core-shell structure. The average size of the NIA-loaded pH-responsive microbeads was 1243.3 ± 11.5 µm. The EE and LC were 33.3 ± 0.5 % and 28.5 ± 0.4 %, respectively. The release profiles of NIA showed pH-responsive properties, as 94.2 ± 3.5 % of NIA was released at pH 5.5, whereas 99.3 ± 2.4 % of NIA was released at pH 7.0. The NIA-loaded pH-responsive PHB/CAP microbeads were stable for >90 days at 4 °C under darkness, with NIA remaining at 73.65 ± 1.86 %. A cytotoxicity assay in PSVK1 cells confirmed that the NIA-loaded pH-responsive PHB/CAP microbeads were nontoxic at concentrations lower than 31.3 µg/mL, in accordance with ISO 10993-5.

Fabrication, characterization and release behavior of α-tocopherol acetate-loaded pH-responsive polyhydroxybutyrate/cellulose acetate phthalate microbeads.

Microbeads are used in personal care and cosmetic products (PCCPs) but are produced from nondegradable materials. Biodegradable polyhydroxybutyrate (PHB) has been recognized as a promising alternative material for use in PCCPs; however, utilizing PHB to encapsulate PCCPs is challenging because PCCPs need to be protected from the environment but their release needs to be permitted under specific physiological conditions. The aim of this work was to develop and evaluate pH-responsive cellulose acetate phthalate (CAP) to formulate lipophilic α-tocopherol acetate (α-TA)-loaded pH-responsive PHB/CAP microbeads. The influences of the PHB/CAP ratio and initial α-TA loading on the microbead size, surface morphology, encapsulation efficiency (%EE), loading capacity (%LC), and α-TA release profile were studied. The microbeads exhibited a spherical shape with a size of 328.7 ± 2.9 µm. The EE and LC were 86.7 ± 2.6 % and 13.5 ± 0.4 %, respectively. The release profile exhibited pH-responsive characteristics. These α-TA-loaded pH-responsive microbeads were stable with >50 % of the α-TA remaining after 90 days at 4, 25 and 45 °C in the dark. The results from the cytotoxicity assay with PSVK1 cells demonstrated that the microbeads were nontoxic. Hence, our developed formulation has the potential to be used to encapsulate oil-based drugs to formulate lipophilic substance-loaded pH-responsive microbeads.

Preparation and characterization of astaxanthin-loaded biodegradable polyhydroxybutyrate (PHB) microbeads for personal care and cosmetic applications.

Due to its biodegradability and biocompatibility, polyhydroxybutyrate (PHB) has received attention as an alternative material for microbeads in personal care and cosmetic products (PCCPs). Here, PHB was produced from crude glycerol by an Escherichia coli JM109 strain harboring pUC19-23,119-phaCABA-04 without isopropyl ß-D-1-thiogalactopyranoside (IPTG), an inducing agent. Astaxanthin-loaded PHB microbeads were prepared through emulsification-solvent evaporation. Studies were performed to determine how the concentration of PHB and stirring rate influence the size, surface morphology, encapsulation efficiency (EE), and astaxanthin release profile. The astaxanthin-loaded PHB microbeads exhibited a rough surface, 98.1 ± 0.7 % EE, spherical shape and 179 ± 44 µm size. In addition, <50 % astaxanthin release was observed within 240 min. Stability studies revealed that astaxanthin-loaded microbeads retained over 85.3 ± 4.2 % of astaxanthin after 90 days at 4 °C and showed a 2-fold reduction in astaxanthin degradation compared to their unencapsulated counterparts; thus, astaxanthin-loaded microbeads show promise for PCCPs applications. A cytotoxicity assay revealed that astaxanthin-loaded PHB microbeads were nontoxic to the human epidermal keratinocyte cell line, PSVK1, and EpiSkin® cells. Skin irritation and sensitization were not observed during a human repeated insult patch test (HRIPT), according to clinical practice guidelines of the Japanese dermatological association.