In this study, a system for oral delivery of oxaliplatin (OXA) was prepared for metronomic chemotherapy to enhance antitumor efficacy and modulate tumor immunity. OXA was complexed with ...Nα-deoxycholyl-l-lysyl-methylester (DCK) (OXA/DCK) and formulated as a nanoemulsion (OXA/DCK-NE). OXA/DCK-NE showed 3.35-fold increased permeability across a Caco-2 cell monolayer, resulting in 1.73-fold higher oral bioavailability than free OXA. In addition, treatment of the B16F10.OVA cell line with OXA/DCK-NE resulted in successful upregulation of immunogenic cell death (ICD) markers both in vitro and in vivo. In a B16F10.OVA tumor-bearing mouse model, treatment with OXA/DCK-NE substantially impeded tumor growth by 63.9 ± 13.3% compared to the control group, which was also greater than the intravenous (IV) OXA group. Moreover, treatment with a combination of oral OXA/DCK-NE and anti-programmed cell death protein-1 (αPD-1) antibody resulted in 78.3 ± 9.67% greater inhibition compared to controls. More important, OXA/DCK-NE alone had immunomodulatory effects, such as enhancement of tumor antigen uptake, activation of dendritic cells in tumor-draining lymph nodes, and augmentation of both the population and function of immune effector cells in tumor tissue as well as in the spleen; no such effects were seen in the OXA IV group. These observations provide a rationale for combining oral metronomic OXA with immunotherapy to elicit synergistic antitumor effects.
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•OXA/DCK-NE was permeated through intestine via bile acid transport-mediated uptake.•The oral bioavailability of OXA/DCK-NE was greater than that of free oxaliplatin.•Oral metronomic OXA/DCK-NE treatment effectively modulated tumor immunity.•OXA/DCK-NE induced immunogenic cell death and enhanced immune cell numbers.•OXA/DCK-NE and αPD-1 exhibited synergistic antitumor effects.
Plant-derived compounds, specifically antioxidants, have played an important role in scavenging the free radicals present under diseased conditions. The persistent generation of free radicals in the ...body leads to inflammation and can result in even more severe diseases such as cancer. Notably, the antioxidant potential of various plant-derived compounds prevents and deregulates the formation of radicals by initiating their decomposition. There is a vast literature demonstrating antioxidant compounds' anti-inflammatory, anti-diabetic, and anti-cancer potential. This review describes the molecular mechanism of various flavonoids, such as quercetin, kaempferol, naringenin, epicatechin, and epicatechin gallate, against different cancers. Additionally, the pharmaceutical application of these flavonoids against different cancers using nanotechnologies such as polymeric, lipid-based nanoparticles (solid-lipid and liquid-lipid), liposomes, and metallic nanocarriers is addressed. Finally, combination therapies in which these flavonoids are employed along with other anti-cancer agents are described, indicating the effective therapies for the management of various malignancies.
Middle aortic syndrome (MAS), an uncommon cause of secondary hypertension, is defined by obstructive narrowing of the abdominal aorta and ostia of its major branches like the renal and splanchnic ...arteries. Most of the cases of MAS are categorized as idiopathic; however, genetic disorders like Williams syndrome, mucopolysaccharidosis, neurofibromatosis type 1 (NF1), and Alagille syndrome, and acquired inflammatory diseases such as Takayasu arteritis and other nonspecific arteritis can also lead to MAS. MAS is commonly seen in children and young adults presenting with severe hypertension, congestive heart failure, renal failure, or severe leg claudication. The diagnosis of MAS on CT, MR, and conventional angiography is fairly straightforward. However, the spectrum of sonographic findings in MAS can be varied. Since ultrasound is frequently utilized as a first-line investigation for secondary causes of hypertension, it is especially crucial to understand the sonographic features of MAS. Here, we report a case of a young female who presented to our hospital with severe hypertension. On the Renal Doppler scan, the only clue of the renovascular etiology of her secondary hypertension was the "tardus-parvus waveform'' in the intrarenal arteries.
Background
Effective oral delivery of drugs remains a major challenge given their possible undesirable physicochemical properties, physicochemical factors, and the physiological conditions of the ...gastrointestinal (GI) tract. Continuous efforts have been made to overcome these issues by improving the intestinal permeability and oral bioavailability of drugs. Recently, the strategy to improve intestinal permeability has shifted towards targeting drugs to intestinal membrane transporters.
Area covered
In this review, the usefulness of various solute carrier (SLC) and ATP (adenosine triphosphate)-binding cassette (ABC) transporters that are widely expressed in the intestinal epithelia and their impact on increasing the membrane permeability and oral bioavailability of drugs are discussed.
Expert opinion
Targeting intestinal membrane transporters has emerged as a promising avenue to increase the oral absorption of drugs. Recently, several approaches that target intestinal membrane transporters have resulted in significant improvements in oral bioavailability, such as the use of absorption enhancers or excipients, modification of a drug’s physicochemical properties, and/or the development of novel drug delivery vehicles that enhance drug influx and inhibit efflux. Additionally, efforts have been made to elucidate the role of dual-transporter targeting in drug delivery. Therefore, implementation of transporter-mediated drug-delivery strategies may be a promising approach to increase oral bioavailability.
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Osteoarthritis (OA) is a well-known degenerative joint disease recognized by the deterioration of cartilage in the joints, leading to pain and reduced mobility. Traditional treatments ...for OA include pain management, physical therapy, and in severe cases, joint replacement surgery. In recent years, there has been growing interest in exploring the potential of phytoconstituents and nanomedicines combined for treating OA. Furthermore, with the increasing amount of study in this field, now is the opportune time for the widespread use of plant-derived medications as complementary and alternative medical therapies to be acknowledged and used for more efficient treatment of human ailments like OA. Combining phytoconstituents with nanomedicine technology (phyto-nanomedicine) can potentially enhance their effectiveness in treating OA. The phyto-nanomedicines has many advantages, including enhanced permeability, increased bioavailability, and sustained/controlled drug release at the joint site, decreased adverse effects, and possible use in combination treatment. It’s important to note that while there is promising preclinical and some clinical evidence regarding the effectiveness of phyto-nanomedicine in OA treatment, further research is needed to establish their safety and efficacy conclusively. In this review, the effectiveness of phytoconstituents to treat OA and the potential of combining phytomedicines with nanoparticulate drug delivery to enhance the former therapeutic effectiveness is discussed in detail. Furthermore, we have also described briefly on the application of organ-on-chip and/or joint on-chip models to accelerate the identification of novel phytoconstituents and evaluate the potency of phyto-nanomedicines to treat OA.
The metabolic syndrome (MetS), first introduced by Haller in 1975, was sometimes also known as insulin resistance syndrome, syndrome X, and plurimetabolic syndrome. In 1989, it was rechristened by ...Kaplan as the “Deadly Quartet” based on a consolidation of central obesity, impaired glucose tolerance, dyslipidemia, and systemic hypertension. MetS is positively associated with a pro-inflammatory and pro-thrombotic state, attributed to increased pro-thrombotic and inflammatory marker activity. Moreover, MetS is frequently associated with increased atherosclerotic cardiovascular disease, impaired glucose tolerance, hyperuricemia, obstructive sleep apnea, and chronic kidney disease. Despite concerted endeavors worldwide, the complexity of the pathophysiology of metabolic syndrome still needs to be clearly understood. Currently, therapeutic possibilities are confined to individual therapy for hyperglycemia, hypertension, hypertriglyceridemia, hyperuricemia, regular physical exercise, and a restricted diet. In this review, progress regarding the understanding and pathophysiology of MetS; recent emerging technologies, such as metabolomics and proteomics; the relation of MetS with obesity, diabetes, and cardiovascular diseases; and the association of MetS with COVID-19 are discussed.
Respiratory diseases contribute to a significant percentage of mortality and morbidity worldwide. The circadian rhythm is a natural biological process where our bodily functions align with the 24 h ...oscillation (sleep-wake cycle) process and are controlled by the circadian clock protein/gene. Disruption of the circadian rhythm could alter normal lung function. Chronotherapy is a type of therapy provided at specific time intervals based on an individual's circadian rhythm. This would allow the drug to show optimum action, and thereby modulate its pharmacokinetics to lessen unwanted or unintended effects. In this review, we deliberated on the recent advances employed in chrono-targeted therapeutics for chronic respiratory diseases.
Serratiopeptidase (SRP) is a proteolytic enzyme that emerged as one of the most potent anti-inflammatory and analgesic drugs. The purpose of the present study was to formulate and evaluate ...enteric-coated tablets for SRP and investigate their stability using a simple and validated analytical method by ultraviolet (UV) spectroscopy. The colloidal silicon dioxide (2.50%), sodium starch glycolate (3.44%), and crospovidone (2.50%) were used as appropriate excipients for the development of core part of tablets. To protect the prepared tablets from acidic environment in the stomach, white shellac, castor oil, HPMC phthalate 40, and ethyl cellulose were used. The seal coating and enteric coating attained were 2.75% and 6.74%, respectively. SRP was found to be linear at 265 nm in the concentration range of 25–150 µg/mL. The results revealed that our developed method was linear (R2 = 0.999), precise (RSD % = 0.133), and accurate (% recovery = 99.96–103.34). The formulated SRP tablets were found to be stable under accelerated conditions as well as under room temperature for 6 months (assay %: >97.5%). The in vitro drug release study demonstrated that enteric-coated tablets were able to restrict SRP release in both acidic environments: 0.1 N HCl and simulated gastric fluid (pH 1.2). Moreover, at 60 minutes, the formulated SRP tablets revealed 13.0% and 8.98% higher drug release in phosphate buffer (pH 6.8) and simulated intestinal fluid (pH 6.8), respectively, compared to the marketed tablet formulation. This study concludes that enteric-coated tablets of SRP with higher drug release in the intestine can be prepared and examined for their stability using validated analytical technique of UV spectroscopy.
Antibiotic resistance has become a threat to microbial therapies nowadays. The conventional approaches possess several limitations to combat microbial infections. Therefore, to overcome such ...complications, novel drug delivery systems have gained pharmaceutical scientists' interest. Significant findings have validated the effectiveness of novel drug delivery systems such as polymeric nanoparticles, liposomes, metallic nanoparticles, dendrimers, and lipid-based nanoparticles against severe microbial infections and combating antimicrobial resistance. This review article comprises the specific mechanism of antibiotic resistance development in bacteria. In addition, the manuscript incorporated the advanced nanotechnological approaches with their mechanisms, including interaction with the bacterial cell wall, inhibition of biofilm formations, activation of innate and adaptive host immune response, generation of reactive oxygen species, and induction of intracellular effect to fight against antibiotic resistance. A section of this article demonstrated the findings related to the development of delivery systems. Lastly, the role of microfluidics in fighting antimicrobial resistance has been discussed. Overall, this review article is an amalgamation of various strategies to study the role of novel approaches and their mechanism to fight against the resistance developed to the antimicrobial therapies.
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