The ubiquitous physiology of nitric oxide enables the bioinorganic engineering of [Fe(NO)2]-containing and NO-delivery scaffolds for tissue engineering.

Bioavailability plays an important role in drug activity in the human body, as certain drug amounts should be present to elicit activity. However, low bioavailability of drugs leads to negligible use for human benefit. In this study, the diversely active neolignan, magnolol, was impregnated onto a Zr-based organometallic framework [Uio-66(Zr)] to increase its low bioavailability (4–5%) and to test its potential acute oral toxicity. Synthesis of Uio-66(Zr) was done through the solvothermal method while simple impregnation at different time points was used to incorporate magnolol. The loading capacity of Uio-66(Zr) at 36 h was found to be significantly higher at 72.16 ± 2.15% magnolol than in other incubation time. Based on the OECD 425 (limit test), toxicity was not observed at 2000 mg kg−1 dose of mag@Uio-66(Zr) in female Sprague Dawley rats. The area under the curve (AUC) at 0–720 min of mag@Uio-66(Zr) was significantly higher than the AUC of free magnolol. Moreover, relative bioavailability increased almost two-folds using Uio-66(Zr). Unconjugated magnolol was found in the liver, kidney, and brain of rats in all treatment groups. Collectively, Uio-66(Zr) provided a higher magnolol bioavailability when used as drug carrier. Thus, utilization of Uio-66(Zr) as drug carrier is of importance for maximal use for poorly soluble and lowly bioavailable drugs.

The phenolic natural product magnolol exhibits neuroprotective properties through β-amyloid toxicity in PC-12 cells and ameliorative effects against cognitive deficits in a TgCRND8 transgenic mice model. Its bioavailability and blood–brain barrier crossing ability have been significantly improved using the metal–organic framework (MOF) UiO-66­(Zr) as a drug delivery system (DDS). To investigate the neuroprotective effects of the Zr-based DDS, magnolol and magnolol-loaded-UiO-66­(Zr) (Mag@UiO-66­(Zr)) were evaluated for inhibitory activity against β-secretase and AlCl3-induced neurotoxicity. Due to the moderate inhibition observed for magnolol in vitro, in silico binding studies were explored against β-secretase along with 11 enzymes known to affect Alzheimer’s disease (AD). Favorable binding energies against CDK2, CKD5, MARK, and phosphodiesterase 3B (PDE3B) and dynamically stable complexes were noted through molecular docking and molecular dynamic simulation experiments, respectively. The magnolol-loaded DDS UiO-66­(Zr) also showed enhanced neuroprotective activity against two pathological indices, namely, neutrophil infiltration and apoptotic neurons, in addition to damage reversal compared to magnolol. Thus, MOFs are promising drug delivery platforms for poorly bioavailable drugs.

RESUMO-Neste trabalho foi investigado o processo de produção de Biocombustíveis via Craqueamento Térmo-Catalítico do Material Lipídico das Caixas de Gordura do RU-UFPA. O Material Residual das Caixas de Gordura após coletado foi submetido a uma série de Operações de Separação Físicas (Peneiramento, Decantação, e Desidratação) em uma Unidade Piloto de Desodorização, objetivando a remoção dos sólidos em suspenção, a formação do sistema bifásico Gordura Residual-Fase Aquosa, a remoção da Fase Aquosa, e a desidratação parcial e homogeneização da Gordura Residual. Em seguida, a Gordura Residual foi processada na Unidade Piloto de Craqueamento a 450ºC, 150 rpm, e 10% (m/m) de Na2CO3 como catalisador. A Fase Aquosa foi submetida às analises físico-químicas e bacteriológicas conforme os Métodos Oficiais da APHA, enquanto a Gordura Residual foi analisada de acordo com os Métodos Oficiais AOCS e ASTM. O Produto Líquido Orgânico (PLO), condensado obtido na reação com I.A = 14.97 mgKOH/gPLO e rendimento em Basa Seca de 68.72 %, foi fracionado em uma Unidade Piloto de Destilação, objetivando obter Frações de Biocombustíveis semelhantes ao Querosene, sendo o rendimento da Fração de Querosene de 15.07 %. O PLO e a Fração Destilada de Biocombustível (Querosene Verde) foram analisados de acordo com os Métodos Oficiais AOCS e ASTM.