Preparation and in vitro/in vivo evaluation of azilsartan osmotic pump tablets based on the preformulation investigation.

The objective of this study was to design and evaluate azilsartan osmotic pump tablets. Preformulation properties of azilsartan were investigated for formulation design. Azilsartan osmotic pump tablets were prepared by incorporation of drug in the core and subsequent coating with cellulose acetate and polyethylene glycol 4000 as semi-permeable membrane, then drilled an orifice at the center of one side. The influence of different cores, compositions of semipermeable membrane and orifice diameter on azilsartan release were evaluated. The formulation of core tablet was optimized by orthogonal design and the release profiles of various formulations were evaluated by similarity factor (f2). The optimal formulation achieved to deliver azilsartan at an approximate zero-order up to 14 h. The pharmacokinetic study was performed in beagle dogs. The azilsartan osmotic pump tablets exhibited less fluctuation in blood concentration and higher bioavailability compared to immediate-release tablets. Moreover, there was a good correlation between the in vitro dissolution and in vivo absorption of the tablets. In summary, azilsartan osmotic pump tablets presented controlled release in vitro, high bioavailability in vivo and a good in vitro-in vivo correlation.

A Bioinspired Skin UV Filter with Broadband UV Protection, Photostability, and Resistance to Oxidative Damage.

In recent years, sunscreens' adverse impacts on the environment and biology have gained wide attention. The improvement of sunscreen safety has become one of the major priorities in skin photoprotection research. It is an effective strategy to develop bionic photoprotective materials by simulating the photoprotective mechanism existing in nature. Inspired by the photoprotective mechanisms of skin and plant leaves, the bionic photoprotective material CS-SA-PDA nanosheet was developed using the free radical grafting method and Michael addition, with natural melanin analogue polydopamine (PDA) nanoparticles and plant sunscreen molecular sinapic acid (SA) as sun protection factors and natural polymer chitosan (CS) as the connecting arm. The results show that CS-SA-PDA can effectively shield UVB and UVA due to the possible synergistic effect between PDA and SA. The introduction of polymer CS significantly improved the photostability of SA and reduced the skin permeability of PDA nanoparticles. The CS-SA-PDA nanosheet can also effectively scavenge photoinduced free radicals. Furthermore, in vivo toxicity and anti-UV evaluations confirm that CS-SA-PDA has no skin irritation and is excellent against skin photodamage, which makes it an ideal skin photoprotective material.

Functional composite hydrogels entrapping polydopamine hollow nanoparticles for highly efficient resistance of skin penetration and photoprotection.

Living organisms tend to evolve various naturally photoprotective mechanisms to avoid photodamage. Among them, polydopamine (PDA) is an effective sunscreen, a mimic of melanin, which is the main functional component of the photoprotective system of human skin. However, the concerns of its dark color, skin penetration and photoprotective efficiency remain yet to be solved. Herein, we have constructed melanin-inspired nanocomposite hydrogels (CS-PDAh-GP-HA) for photoprotection, in which PDA was prepared as hollow nanoparticles (PDAh NPs) and entrapped in a physically cross-linked hydrogel (CS-GP-HA) formed by chitosan (CS) and hyaluronic acid (HA) using ß-glycerophosphate (ß-GP) as a modulator. The CS-PDAh-GP-HA hydrogels exhibit a shear-thinning flow behavior with an elastic modulus of 300 Pa with the gel-sol transition temperature maintained at about 37 °C simply by adjusting the ß-GP content in the hydrogels. The CS-PDAh-GP-HA hydrogels also possess excellent resistance toward skin penetration. The photoprotective performances of CS-PDAh-GP-HA hydrogels were evaluated by the determination of sun protection factor (SPF) and in vitro UVA protection efficacy (UVAPE) along with UV-Vis spectroscopy. Compared with the TiO2 nanoparticles in CS-GP-HA hydrogel, the CS-PDAh-GP-HA hydrogels show stronger shielding ability in both UVA and UVB regions. When protected by the CS-PDAh-GP-HA hydrogels, the cell viability of NIH-3T3 fibroblasts increases to 96% while it was only 14% in the case of non-protecting group. These results suggest that the CS-PDAh-GP-HA hydrogels could efficiently shield the UV irradiation and protect the skin from photodamage. This work introduces PDA-based nanocomposite hydrogels with safe, biocompatible and photoprotective properties, and provides a melanin-mimicking photoprotection system for the application in sunscreens.

PEG-lipid-PLGA hybrid nanoparticles loaded with berberine-phospholipid complex to facilitate the oral delivery efficiency.

The natural product berberine (BBR), present in various plants, arouses great interests because of its numerous pharmacological effects. However, the further development and application of BBR had been hampered by its poor oral bioavailability. In this work, we report on polymer-lipid hybrid nanoparticles (PEG-lipid-PLGA NPs) loaded with BBR phospholipid complex using a solvent evaporation method for enhancing the oral BBR efficiency. The advantage of this new drug delivery system is that the BBR-soybean phosphatidylcholine complex (BBR-SPC) could be used to enhance the liposolubility of BBR and improve the affinity with the biodegradable polymer to increase the drug-loading capacity and controlled/sustained release. The entrapment efficiency of the PEG-lipid-PLGA NPs/BBR-SPC was observed to approach approximately 89% which is more than 2.4 times compared with that of the PEG-lipid-PLGA NPs/BBR. To the best of our knowledge, this is the first report on using polymer material for effective encapsulation of BBR to improve its oral bioavailability. The prepared BBR delivery systems demonstrated a uniform spherical shape, a well-dispersed core-shell structure and a small particle size (149.6 ± 5.1 nm). The crystallographic and thermal analysis has indicated that the BBR dispersed in the PEG-lipid-PLGA NPs matrix is in an amorphous form. More importantly, the enhancement in the oral relative bioavailability of the PEG-lipid-PLGA NPs/BBR-SPC was ∼343% compared with that of BBR. These positive results demonstrated that PEG-lipid-PLGA NPs/BBR-SPC may have the potential for facilitating the oral drug delivery of BBR.