Microwave-assisted extraction of polysaccharide from Cinnamomum cassia with anti-hyperpigmentation properties: Optimization and characterization studies.

The anti-hyperpigmentation effect and tyrosinase inhibitory mechanism of cinnamon polysaccharides have not been reported. The current study focused on the extraction of polysaccharides from Cinnamomum cassia bark using microwave-assisted approach and optimization of the extraction process (i.e., microwave power, irradiation time and buffer-to-sample ratio) by Box-Behnken design to obtain a high yield of polysaccharides with high sun protection factor (SPF), anti-hyperpigmentation and antioxidant activities. The extracted pectic-polysaccharides had low molecular weight and degree of esterification. The optimal extraction process had polysaccharides characterized by (a) monophenolase inhibitory activity = 97.5 %; (b) diphenolase inhibitory activity = 99.4 %; (c) ferric reducing antioxidant power = 4.4 mM; (d) SPF = 6.1; (e) yield = 13.7 %. The SPF, tyrosinase inhibitory and antioxidant activities were primarily contributed by the polysaccharides. In conclusion, the polysaccharides from C. cassia could be an alternative therapeutic source for skin hyperpigmentation treatment.

Effects of Drug-Free Pectin Hydrogel Films on Thermal Burn Wounds in Streptozotocin-Induced Diabetic Rats.

This study aims to examine the influence of drug-free pectin hydrogel films on partial-thickness burn wounds using streptozotocin-induced diabetic rats as the animal model. Thirty male Sprague Dawley rats were included in the wound healing study, and scalding water was used to produce wounds in the dorsum region of the rats. Two different formulations of pectin hydrogel films, PH 2.5% and PH 5%, were prepared using a solvent evaporation method. MEBO® (moist exposed burn ointment), a commercial herbal formulation was used as a positive control. The progress of the wound healing was observed and compared between untreated normal rats, untreated diabetic rats, diabetic rats treated with MEBO®, diabetic rats treated with PH 2.5%, and diabetic rats treated with PH 5%. The results showed that diabetic rats treated with PH 5% healed faster than the untreated diabetic rats and diabetic rats treated with PH 2.5%. Interestingly, the diabetic rats treated with PH 5% healed as well as diabetic rats treated with MEBO®, where wounds were healed entirely on day 20. Nevertheless, both PH 2.5% and PH 5% showed a greater zone of inhibition than MEBO® when tested against Staphylococcus aureus.

Effect of Chicken Egg White-Derived Peptide and Hydrolysates on Abnormal Skin Pigmentation during Wound Recovery.

Abnormal skin pigmentation commonly occurs during the wound healing process due to the overproduction of melanin. Chicken egg white (CEW) has long been used to improve skin health. Previous published works had found CEW proteins house bioactive peptides that inhibit tyrosinase, the key enzyme of melanogenesis. The current study aimed to evaluate the anti-pigmentation potential and mechanism of the CEW-derived peptide (GYSLGNWVCAAK) and hydrolysates (CEWHmono and CEWHdi), using a cell-based model. All of these peptide and hydrolysates inhibited intracellular tyrosinase activity and melanin level up to 45.39 ± 1.31 and 70.01 ± 1.00%, respectively. GYSLGNWVCAAK and CEWHdi reduced intracellular cAMP levels by 13.38 ± 3.65 and 14.55 ± 2.82%, respectively; however, CEWHmono did not affect cAMP level. Moreover, the hydrolysates downregulated the mRNA expression of melanogenesis-related genes, such as Mitf, Tyr, Trp-1 and Trp-2, but GYSLGNWVCAAK only suppressed Tyr gene expression. Downregulation of the genes may lower the catalytic activities and/or affect the structural stability of TYR, TRP-1 and TRP-2; thus, impeding melanogenesis to cause an anti-pigmentation effect in the cell. Outcomes from the current study could serve as the starting point to understand the underlying complex, multifaceted melanogenesis regulatory mechanism at the cellular level.

Probing Critical Physical Properties of Lactose-Polyethylene Glycol Microparticles in Pulmonary Delivery of Chitosan Nanoparticles.

Pulmonary delivery of chitosan nanoparticles is met with nanoparticle agglomeration and exhalation. Admixing lactose-based microparticles (surface area-weighted diameter~5 µm) with nanoparticles mutually reduces particle agglomeration through surface adsorption phenomenon. Lactose-polyethylene glycol (PEG) microparticles with different sizes, morphologies and crystallinities were prepared by a spray drying method using varying PEG molecular weights and ethanol contents. The chitosan nanoparticles were similarly prepared. In vitro inhalation performance and peripheral lung deposition of chitosan nanoparticles were enhanced through co-blending with larger lactose-PEG microparticles with reduced specific surface area. These microparticles had reduced inter-microparticle interaction, thereby promoting microparticle-nanoparticle interaction and facilitating nanoparticles flow into peripheral lung.

Design of oral intestinal-specific alginate-vitexin nanoparticulate system to modulate blood glucose level of diabetic rats.

Vitexin of Ficus deltoidea exhibits intestinal α-glucosidase inhibitory and blood glucose lowering effects. This study designs oral intestinal-specific alginate nanoparticulate system of vitexin. Nanospray-dried alginate, alginate/stearic acid and alginate-C18 conjugate nanoparticles were prepared. Stearic acid was adopted to hydrophobize the matrix and minimize premature vitexin release in stomach, whereas C-18 conjugate as immobilized fatty acid to sustain hydrophobic effect and drug release. Nanoparticles were compacted with polyethylene glycol (PEG 3000, 10,000 and 20,000). The physicochemical, drug release, in vivo blood glucose lowering and intestinal vitexin content of nanoparticles and compact were determined. Hydrophobization of alginate nanoparticles promoted premature vitexin release. Compaction of nanoparticles with PEG minimized vitexin release in the stomach, with stearic acid loaded nanoparticles exhibiting a higher vitexin release in the intestine. The introduction of stearic acid reduced vitexin-alginate interaction, conferred alginate-stearic acid mismatch, and dispersive stearic acid-induced particle breakdown with intestinal vitexin release. Use of PEG 10,000 in compaction brought about PEG-nanoparticles interaction that negated initial vitexin release. The PEG dissolution in intestinal phase subsequently enabled particle breakdown and vitexin release. The PEG compacted nanoparticles exhibited oral intestinal-specific vitexin release, with positive blood glucose lowering and enhanced intestinal vitexin content in vivo.

Critical physicochemical attributes of chitosan nanoparticles admixed lactose-PEG 3000 microparticles in pulmonary inhalation.

Chitosan nanoparticles are exhalation prone and agglomerative to pulmonary inhalation. Blending nanoparticles with lactose microparticles (∼5 µm) could mutually reduce their agglomeration through surface adsorption phenomenon. The chitosan nanoparticles of varying size, size distribution, zeta potential, crystallinity, shape and surface roughness were prepared by spray drying technique as a function of chitosan, surfactant and processing conditions. Lactose-polyethylene glycol 3000 (PEG3000) microparticles were similarly prepared. The chitosan nanoparticles, physically blended with fine lactose-PEG3000 microparticles, exhibited a comparable inhalation performance with the commercial dry powder inhaler products (fine particle fraction between 20% and 30%). Cascade impactor analysis indicated that the aerosolization and inhalation performance of chitosan nanoparticles was promoted by their higher zeta potential and circularity, and larger size attributes of which led to reduced inter-nanoparticulate aggregation and favored nanoparticles interacting with lactose-PEG3000 micropaticles that aided their delivery into deep and peripheral lungs.

Coatless alginate pellets as sustained-release drug carrier for inflammatory bowel disease treatment.

Conventional alginate pellets underwent rapid drug dissolution and failed to exert colon targeting unless subjected to complex coating. This study designed coatless delayed-release oral colon-specific alginate pellets for ulcerative colitis treatment. Alginate pellets, formulated with water-insoluble ethylcellulose and various calcium salts, were prepared using solvent-free melt pelletization technique which prevented reaction between processing materials during agglomeration and allowed reaction to initiate only in dissolution. Combination of acid-soluble calcium carbonate and highly water-soluble calcium acetate did not impart colon-specific characteristics to pellets due to pore formation in fragmented matrices. Combination of moderately water-soluble calcium phosphate and calcium acetate delayed drug release due to rapid alginate crosslinking by soluble calcium from acetate salt followed by sustaining alginate crosslinking by calcium phosphate. The use of 1:3 ethylcellulose-to-alginate enhanced the sustained drug release attribute. The ethylcellulose was able to maintain the pellet integrity without calcium acetate. Using hydrophobic prednisolone as therapeutic, hydrophilic alginate pellets formulated with hydrophobic ethylcellulose and moderately polar calcium phosphate exhibited colon-specific in vitro drug release and in vivo anti-inflammatory action. Coatless oral colon-specific alginate pellets can be designed through optimal formulation with melt pelletization as the processing technology.

In Vitro Investigation of Influences of Chitosan Nanoparticles on Fluorescein Permeation into Alveolar Macrophages.

PURPOSE: Pulmonary infection namely tuberculosis is characterized by alveolar macrophages harboring a large microbe population. The chitosan nanoparticles exhibit fast extracellular drug release in aqueous biological milieu. This study investigated the matrix effects of chitosan nanoparticles on extracellular drug diffusion into macrophages. METHODS: Oligo, low, medium and high molecular weight chitosan nanoparticles were prepared by nanospray drying technique. These nanoparticles were incubated with alveolar macrophages in vitro and had model drug sodium fluorescein added into the same cell culture. The diffusion characteristics of sodium fluorescein and nanoparticle behavior were investigated using fluorescence microscopy, scanning electron microscopy, differential scanning calorimetry and Fourier transform infrared spectroscopy techniques. RESULTS: The oligochitosan nanoparticles enabled macrophage membrane fluidization with the extent of sodium fluorescein entry into macrophages being directly governed by the nanoparticle loading. Using nanoparticles made of higher molecular weight chitosan, sodium fluorescein permeation into macrophages was delayed due to viscous chitosan diffusion barrier at membrane boundary. CONCLUSION: Macrophage-chitosan nanoparticle interaction at membrane interface dictates drug migration into cellular domains.