Non-steroidal anti-inflammatory drugs (NSAIDs) express anti-tumoral activity mainly by blocking cyclooxygenase-2 involved in the synthesis of prostaglandins. Therefore, in the last few decades, many have attempted to explore the possibilities of applying this group of drugs as effective agents for the inhibition of neoplastic processes. This review summarizes the evidence presented in the literature regarding the anti-tumoral actions of NSAIDs used as monotherapies as well as in combination with conventional chemotherapeutics and natural products. In several clinical trials, it was proven that combinations of NSAIDs and chemotherapeutic drugs (CTDs) were able to obtain suitable results. The combination with phospholipids may resolve the adverse effects of NSAIDs and deliver derivatives with increased antitumor activity, whereas hybrids with terpenoids exhibit superior activity against their parent drugs or physical mixtures. Therefore, the application of NSAIDs in cancer therapy seems to be still an open chapter and requires deep and careful evaluation. The literature’s data indicate the possibilities of re-purposing anti-inflammatory drugs currently approved for cancer treatments.
The aim of this work was to design innovative nanostructured lipid carriers (NLCs) for the delivery of dexibuprofen (DXI) as an antiproliferative therapy against tumoral processes, and overcome its side effects. DXI-NLC samples were prepared with beeswax, Miglyol 812 and Tween 80 using high-pressure homogenization. A two-level factorial design 24 was applied to optimize the formulation, and physicochemical properties such as particle size, zeta potential, polydispersity index and entrapment efficiency were measured. Optimized parameters of DXI-NLCs exhibited a mean particle size of 152.3 nm, a polydispersity index below 0.2, and high DXI entrapment efficiency (higher than 99%). Moreover, DXI-NLCs provided a prolonged drug release, slower than the free DXI. DXI-NLCs were stable for 2 months and their morphology revealed that they possess a spherical shape. In vitro cytotoxicity and anticancer potential studies were performed towards prostate (PC-3) and breast (MDA-MB-468) cancer cell lines. The highest activity of DXI-NLCs was observed towards breast cancer cells, which were effectively inhibited at 3.4 μM. Therefore, DXI-NLCs constitute a promising antiproliferative therapy that has proven to be especially effective against breast cancer.
Background: Aedes aegyptimosquito, the principal global vector of arboviral diseases, lays eggs and undergoes larval and pupal development to become adult mosquitoes in fresh water (FW). It has recently been observed to develop in coastal brackish water (BW) habitats of up to 50% sea water, and such salinity tolerance shown to be an inheritable trait. Genomics of salinity tolerance inAe. aegyptihas not been previously studied, but it is of fundamental biological interest and important for controlling arboviral diseases in the context of rising sea levels increasing coastal ground water salinity.Results: BW- and FW-Ae. aegyptiwere compared by RNA-seq analysis on the gut, anal papillae and rest of the carcass in fourth instar larvae (L4), proteomics of cuticles shed when L4 metamorphose into pupae, and transmission electron microscopy of cuticles in L4 and adults. Genes for specific cuticle proteins, signalling proteins, moulting hormone-related proteins, membrane transporters, enzymes involved in cuticle metabolism, and cytochrome P450 showed different mRNA levels in BW and FW L4 tissues. The salinity-tolerantAe. aegyptiwere also characterized by altered L4 cuticle proteomics and changes in cuticle ultrastructure of L4 and adults.Conclusions: The findings provide new information on molecular and ultrastructural changes associated with salinity adaptation in FW mosquitoes. Changes in cuticles of larvae and adults of salinity-tolerantAe. aegyptiare expected to reduce the efficacy of insecticides used for controlling arboviral diseases. Expansion of coastal BW habitats and their neglect for control measures facilitates the spread of salinity-tolerantAe. aegyptiand genes for salinity tolerance. The transmission of arboviral diseases can therefore be amplified in multiple ways by salinity-tolerantAe. aegyptiand requires appropriate mitigating measures. The findings inAe. aegypti have attendant implications for the development of salinity tolerance in other fresh water mosquito vectors and the diseases they transmit.
1 July 2024 in International Journal of Nanomedicine
Purpose: The anticancer potential of indomethacin and other nonsteroidal anti-inflammatory drugs (NSAIDs) in vitro, in vivo, and in clinical trials is well known and widely reported in the literature, along with their side effects, which are mainly observed in the gastrointestinal tract. Here, we present a strategy for the application of the old drug indomethacin as an anticancer agent by encapsulating it in nanostructured lipid carriers (NLC). We describe the production method of IND-NLC, their physicochemical parameters, and the results of their antiproliferative activity against selected cancer cell lines, which were found to be higher compared to the activity of free indomethacin. Methods: IND-NLC were fabricated using the hot high-pressure homogenization method. The nanocarriers were physicochemically characterized, and their biopharmaceutical behaviour and therapeutic efficacy were evaluated in vitro. Results: Lipid nanoparticles IND-NLC exhibited a particle size of 168.1 nm, a negative surface charge (– 30.1 mV), low polydispersity index (PDI of 0.139), and high encapsulation efficiency (over 99%). IND-NLC were stable for over 60 days and retained integrity during storage at 4 °C and 25 °C. The potential therapeutic benefits of IND-NLC were screened using in vitro cancer models, where nanocarriers with encapsulated drug effectively inhibited the growth of breast cancer cell line MDA-MB-468 at dosage 15.7 μM. Conclusion: We successfully developed IND-NLC for delivery of indomethacin to cancer cells and confirmed their antitumoral efficacy in in vitro studies. The results suggest that indomethacin encapsulated in lipid nanoparticles possesses high anticancer potential. Moreover, the presented strategy is highly promising and may offer a new alternative for future therapeutic drug innovations.
Hydrothermal carbonization (HTC) increasingly appears as an eco-friendly method for managing food waste (FW). In this work, a combination of FW was subjected to HTC, and products were critically evaluated. This involved a lab-scale pressure reactor and optimization of HTC conditions: temperature (220-340 °C) and residence time (90-260 min) via central composite design type of response surface methodology (CCD-RSM). Results showed varying temperatures and residence time to impact the hydrochar (HC) and hydrothermal carbonization aqueous phase (HTC-AP) properties. Although HC produced through HTC exhibited lower ash content (55 %) with respect to the raw FW, the heating value of HC ranged from 19.2 to 32.5 MJ/kg. Temperature primarily influenced FW conversion, affecting carbonaceous properties. Saturated fatty acids (SFA) were found to be predominant in the HTC-AP under all tested operating conditions (77.3, 48.4, and 37.1 wt% for HTC at 340, 280, and 220 °C in 180 min, respectively). Total phosphorus recovery in HC and HTC-AP respectively peaked at 340 °C and 220 °C in 180 min. The study concludes that HTC holds promise for energy-dense biofuel production, nutrient recovery, and fostering a circular economy.
Background: Malaria was eliminated from Sri Lanka in 2013. However, the influx of infected travelers and the presence of potent anopheline vectors can re-initiate transmission in Jaffna city, which is separated by a narrow strait from the malaria-endemic Indian state of Tamil Nadu.Methods: Anopheline larvae were collected from different habitats in Jaffna city and the susceptibility of emergent adults to DDT, malathion and deltamethrin investigated.Results: Anopheline larvae were found in wells, surface-exposed drains, ponds, water puddles and water storage tanks, with many containing polluted, alkaline and brackish water.Anopheles culicifacies,An. subpictus,An. stephensiandAn. varunawere identified in the collections. Adults of the four anopheline species were resistant to DDT.Anopheles subpictusandAn. stephensiwere resistant whileAn. culicifaciesandAn. varunawere possibly resistant to deltamethrin.Anopheles stephensiwas resistant,An. subpictuspossibly resistant whileAn. varunaandAn. culicifacieswere susceptible to malathion. DNA sequencing showed a L1014F (TTA to TTC) mutation in the IIS6 transmembrane segment of the voltage-gated sodium channel protein in deltamethrin-resistantAn. subpictus—a mutation previously observed in India but not Sri Lanka.Conclusion: Anopheles subpictusin Jaffna, likeAn. stephensi, may have recently originated in coastal Tamil Nadu. Besides infected overseas travelers, wind- and boat-borne carriage ofPlasmodium-infected anophelines across the Palk Strait can potentially reintroduce malaria transmission to Jaffna city. Adaptation to diverse larval habitats and resistance to common insecticides in anophelines are identified as potential problems for vector control should this happen.