Shilpa Dawre

As per International Diabetes Federation Report 2022, worldwide diabetes mellitus (DM) caused 6.7M moralities and ~537M adults suffering from diabetes mellitus. It is a chronic condition due to β-cell destruction or insulin resistance that leads to insulin deficiency. This review discusses Type-1 DM and Type-2 DM pathophysiology in detail, with challenges in management and treatment. The toxicity issues of conventional drugs and insulin injections are complex to manage. Thus, there is a need for technological intervention. In recent years, nanotechnology has found a fruitful advancement of novel drug delivery systems that might potentially increase the efficacy of anti-diabetic drugs. Amongst nano-formulations, polymeric nanoparticles have been studied to enhance the bioavailability and efficacy of anti-diabetic drugs and insulin. In the present review, we summarized polymeric nanoparticles with different polymers utilized to deliver anti-diabetic drugs with in vitro and in vivo studies. Furthermore, this review also includes the role of receptors and ligands in diabetes mellitus and the utilization of receptor-ligand interaction to develop targeted nanoparticles. Additionally, we discussed the utility of nanoparticles for the delivery of phytoconstituents which aids in protecting the oxidative stress generated during diabetes mellitus. Atlast, this article also comprises of numerous patents that have been filed or granted for the delivery of antidiabetic and anticancer molecules for the treatment of diabetes mellitus and pancreatic cancer.

Background: Angiotensin II type 1 (AT 1) receptor antagonist (angiotensin receptor blocker (ARB) called Olmesartan medoxomil (OLM) prevents angiotensin II from acting on the renin-angiotensin-aldosterone pathway, which is a crucial factor in the development of hypertension. OLM is reported to rapidly hydrolyze into its active metabolite, Olmesartan, in plasma after oral treatment. Objective: The objective of the ongoing study was to develop an easy-to-use, precise, and reliable RP-HPLC method for the determination of Olmesartan in bulk as well as pharmaceutical dosage forms. Methods: The stability indicating HPLC method for assay includes the use of Kromasil 100-5-C8 (100 mm × 4.6 mm) column, UV detector 265 nm, and mobile phase composition was a mixture of Acetonitrile: water (70:30) and flow rate of 1.0 mL/min. ICH guidelines were followed in the method's validation. To assess the method's specificity and stability in showing characteristics, stress degradation studies were carried out. The working standard solution of Olmesartan was exposed to 0.1 N HCl at room temperature, 0.1 N NaOH at room temperature, 30 percent hydrogen peroxide by volume, and UV radiation in order to conduct a degradation study. Results: The retention periods of the drug were found to be 1.36 and 1.47 min for standard and sample solutions, respectively. The degradation behaviour of drug under different conditions was studied. The drug was found susceptible to acidic, alkaline and oxidative conditions while it was found stable in photolytic condition. The developed stability-indicating RP-HPLC method for assay was validated as per ICH Q2 guidelines and the validation parameters such as accuracy, precision and specificity were obtained within the accepted criteria. Conclusion: It may be concluded that this method is stability-indicating and specific and can successfully be applied to analyze tablet dosage form containing Olmesartan.

The advancement of four-dimensional (4D) printing has been fueled by the rise in demand for additive manufacturing and the expansion in shape-memory materials. The printing of smart substances that respond to external stimuli is known as 4D printing. 4D printing allows highly controlled shapes to simulate the physiological milieu by adding time dimensions. The 4D printing is suitable with current progress in smart compounds, printers, and its mechanism of action. The 4D printing paradigm, a revolutionary enhancement of 3D printing, was anticipated by various engineering disciplines. Tissue engineering, medicinal, consumer items, aerospace, and organ engineering use 4D printing technology. The current review mainly focuses on the basics of 4D printing and the methods used therein. It also discusses the time-dependent behavior of stimulus-sensitive compounds, which are widely used in 4D printing. In addition, this review highlights material aspects, specifically related to shape-memory polymers, stimuli-responsive materials (classified as physical, chemical, and biological), and modified materials, the backbone of 4D printing technology. Finally, potential applications of 4D printing in the biomedical sector are also discussed with challenges and future perspectives. Graphical abstract

Background: The combination of doxycycline (DOXY) and rifampicin (RIF) is recom-mended as a treatment therapy for brucellosis by the World Health Organization. Objective: The aim of the current study was to develop and validate the stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) method for the analysis of a combina-tion of doxycycline & rifampicin. Methods: The RP-HPLC method was developed and validated to estimate the doxycycline and ri-fampicin combination as per ICH guidelines. The drug combination solution was exposed to differ-ent stress conditions: acidic, basic, photo-oxidation, and oxidation. Results: The method was found linear in the range of 2 -10μg/mL for both the drugs with a reten-tion time of 3.5 min for doxycycline and 6.5 min for rifampicin at lambda maximum of 350 nm. The RP-HPLC method was precise and accurate with %RSD < 2%. The intra-day and inter-day precisions were calculated and found within the acceptable range of 5%. Both drugs demonstrated good stability in the mobile phase after 6 hours. The LOD and LOQ of doxycycline and rifampicin were 100 ng/mL & 200ng/mL and 150ng/mL & 500ng/mL, respectively. The forced degradation of the combination of drug solutions was performed. The degraded drug peaks were well-resolved from the peaks of drugs. The percentage encapsulation efficiency of doxycycline and rifampicin in the nanoparticle system was assessed by utilizing the validated RP-HPLC method and found >60% (DOXY) and >70% (RIF). Conclusion: The developed RP-HPLC method of DOXY-RIF combination was rapid, accurate, precise, and stability-indicating. The method can be appropriately applied todetecte drugs in the na-noparticulate system.

Introduction: Brucellosis is a zoonotic disease that is prevalent in livestock animals. The bacteria reside inside the macrophage cells of the host. The WHO has endorseda combination treatment therapy for brucellosis against the conventional monotherapy to avoid relapse and resistance. Therefore, we developed nanoparticles incorporating doxycycline and rifampicin in combination. Aim: The aim of the study is to develop polymeric nanoparticles incorporating doxycycline as well as rifampicin and investigate the antibacterial activity of nanoparticles in U937 human macrophage cells infected with B. abortus. Methods: Polymeric nanoparticles were developed by the emulsion-solvent diffusion method, and characterization was performed. Results: The nanoparticles with high entrapment efficiency of both the drugs were developed successfully. Scanning electron microscopy revealed a spherical morphology with a size ranging ~450nm, which can be easily engulfed by the macrophages. Zeta potential confirmed the colloidal stability. Differential scanning calorimetry and X-ray diffraction suggested amorphization of doxycycline and rifampicin in nanoparticles. Fourier transfer infrared spectroscopy could not confirm the interaction of drugs with AOT. In vitro haemolysis study confirmed the safety of nanoparticles (<10%) for IV administration. Further, nanoparticles revealed the sustained release of both drugs, which followed diffusion kinetics. Nanoparticles were found stable for 6 months as per WHO guidelines. The internalization study revealed nanoparticles could be easily uptaken by U-937 human macrophage cells. The efficacy study demonstrated significantly high antibacterial activity of nanoparticles as compared to free drug solution in U937 human macrophages cells infected with Brucella abortus. Conclusion: It can be concluded that the developed nanoparticles entrapping doxycycline and rifampicin combination can be considered as a promising delivery system for enhancing the antibacterial activity against Brucella abortus.

Infectious diseases are caused by various smart pathogens like bacteria, fungi, viruses, and parasites, claiming more than 17M lives globally (1). Currently, we are in the middle of a pandemic that originated from an infectious disease.