Formulation and quality control of Orally Disintegrating Tablets (ODTs): recent advances and perspectives

Orally disintegrating tablets (ODTs) rapidly disintegrate or dissolve in the oral cavity without using water. Demand for ODTs has increased, and the field has overgrown in the pharmaceutical industry and academia. It is reported that ODTs have several advantages over other conventional tablets. Since some of them are absorbed from the mouth, pharynx, and esophagus as the saliva passes down into the stomach, in such cases, the bioavailability of the drug improves meaningfully. Furthermore, the immediate release property of ODTs makes them a popular oral dosage form in patients with swallowing challenges, children, and for cases with a need for rapid onset of action. The current review article explains the features of active ingredients and excipients used in the formulation of ODTs, discusses multiple ODT formulation and preparation techniques with their merits and demerits, and also, offers remedies for problems associated with ODTs. Moreover, quality control steps and required considerations are presented

Immune checkpoints in targeted-immunotherapy of pancreatic cancer: New hope for clinical development

Immunotherapy has been recently considered as a promising alternative for cancer treatment. Indeed, targeting of immune checkpoint (ICP) strategies have shown significant success in human malignancies. However, despite remarkable success of cancer immunotherapy in pancreatic cancer (PCa), many of the developed immunotherapy methods show poor therapeutic outcomes in PCa with no or few effective treatment options thus far. In this process, immunosuppression in the tumor microenvironment (TME) is found to be the main obstacle to the effectiveness of antitumor immune response induced by an immunotherapy method. In this paper, the latest findings on the ICPs, which mediate immunosuppression in the TME have been reviewed. In addition, different approaches for targeting ICPs in the TME of PCa have been discussed. This review has also synopsized the cutting-edge advances in the latest studies to clinical applications of ICP-targeted therapy in PCa

Extractive spectrophotometric speciation of iron (II) and iron (III) using 4-(2-pyridylazo) resorcinol and 1-hexadecylpyridinium bromide with the partial least square method

A novel method has been developed for extractive spectrophotometric determination of Fe(II) and Fe(III) utilising the formation of the colour complexes with PAR, i.e., 4-(2-pyridylazo) resorcinol, their instantaneous ion-pairing with 1-hexadecylpyridinium counter ion (HDP+) in aqueous solution at pH 8.1, and subsequent extraction onto the organic phase of methyl isobutyl ketone (MIBK), where both ion-associates can sensitively be detected spectrophotometrically. A statistical method based on the partial least squares (PLS) has then been used to define amodel between calibration spectra and the corresponding concentrations. The quantitative PLS model was proposed for absorption spectra in the 350-750 nm range from the data obtained by analysing 25 various mixtures of both iron forms. Their concentration in the calibration matrix was 0.3-1.1 ppm for both Fe(II) and Fe(III); the detection limits being estimated to be 0.09 and 0.13 ppm, respectively. The performance of the model proposed has been confirmed by the determination / speciation of Fe(II) and Fe(III) in model solutions and real samples of pharmaceutical formulations

Exosomes as bio-inspired nanocarriers for RNA delivery:preparation and applications

Nanocarriers as drug/biomolecule delivery systems have been significantly developed during recent decades. Given the stability, reasonable delivery efficiency, and safety of nanocarriers, there are several barriers in the fulfillment of successful clinical application of these delivery systems. These challenges encouraged drug delivery researchers to establish innovative nanocarriers with longer circulation time, high stability, and high compatibility. Exosomes are extracellular nanometer-sized vesicles released through various cells. These vesicles serve as nanocarriers, possessing great potential to overcome some obstacles encountered in gene and drug delivery due to their natural affinity to recipient cells and the inherent capability to shuttle the genes, lipids, proteins, and RNAs between cells. So far, there has been a lot of valuable research on drug delivery by exosomes, but research on RNA delivery, especially mRNA, is very limited. Since mRNA-based vaccines and therapies have recently gained particular prominence in various diseases, it is essential to find a suitable delivery system due to the large size and destructive nature of these nucleic acids. That's why we're going to take a look at the unique features of exosomes and their isolation and loading methods, to embrace this idea that exosome-mediated mRNA-based therapies would be introduced as a very efficient strategy in disease treatment within the near future. GRAPHICAL ABSTRACT: [Image: see text

Correction: Nano-immunotherapy: overcoming delivery challenge of immune checkpoint therapy

The original article has been revise

Nano-immunotherapy: overcoming delivery challenge of immune checkpoint therapy

Abstract Immune checkpoint (ICP) molecules expressed on tumor cells can suppress immune responses against tumors. ICP therapy promotes anti-tumor immune responses by targeting inhibitory and stimulatory pathways of immune cells like T cells and dendritic cells (DC). The investigation into the combination therapies through novel immune checkpoint inhibitors (ICIs) has been limited due to immune-related adverse events (irAEs), low response rate, and lack of optimal strategy for combinatorial cancer immunotherapy (IMT). Nanoparticles (NPs) have emerged as powerful tools to promote multidisciplinary cooperation. The feasibility and efficacy of targeted delivery of ICIs using NPs overcome the primary barrier, improve therapeutic efficacy, and provide a rationale for more clinical investigations. Likewise, NPs can conjugate or encapsulate ICIs, including antibodies, RNAs, and small molecule inhibitors. Therefore, combining the drug delivery system (DDS) with ICP therapy could provide a profitable immunotherapeutic strategy for cancer treatment. This article reviews the significant NPs with controlled DDS using current data from clinical and pre-clinical trials on mono- and combination IMT to overcome ICP therapeutic limitations

Dual Blockade of PD-1 and LAG3 Immune Checkpoints Increases Dendritic Cell Vaccine Mediated T Cell Responses in Breast Cancer Model

Purpose Increasing the efficiency of unsuccessful immunotherapy methods is one of the most important research fields. Therefore, the use of combination therapy is considered as one of the ways to increase the effectiveness of the dendritic cell (DC) vaccine. In this study, the inhibition of immune checkpoint receptors such as LAG3 and PD-1 on T cells was investigated to increase the efficiency of T cells in response to the DC vaccine. Methods We used trimethyl chitosan-dextran sulfate-lactate (TMC-DS-L) nanoparticles (NPs) loaded with siRNA molecules to quench the PD-1 and LAG3 checkpoints’ expression. Results Appropriate physicochemical characteristics of the generated NPs led to efficient inhibition of LAG3 and PD-1 on T cells, which was associated with increased survival and activity of T cells, ex vivo. Also, treating mice with established breast tumors (4T1) using NPs loaded with siRNA molecules in combination with DC vaccine pulsed with tumor lysate significantly inhibited tumor growth and increased survival in mice. These ameliorative effects were associated with increased anti-tumor T cell responses and downregulation of immunosuppressive cells in the tumor microenvironment and spleen. Conclusion These findings strongly suggest that TMC-DS-L NPs loaded with siRNA could act as a novel tool in inhibiting the expression of immune checkpoints in the tumor microenvironment. Also, combination therapy based on inhibition of PD-1 and LAG3 in combination with DC vaccine is an effective method in treating cancer that needs to be further studied