Chimeric Antigen Receptor T Cell Therapy and Its Significance in Multiple Myeloma.

Multiple myeloma (MM) has a five-year prevalence worldwide of 230,000 people and is known as the second most common hematological malignancy within the United States. Extensive research has been conducted to gain a wide range of treatment strategies, providing hope to these patients. Combination therapy using chemotherapy, monoclonal antibodies, and immunomodulatory drugs are the current management of choice. After the introduction of chimeric antigen receptor (CAR) T cell therapy, promising results have been evidenced. In this therapy, T cells are derived from the patient and modified in-vitro to induce receptors that later target specific antigens when they are injected into patients. CAR T cells use three mechanisms to kill tumor cells: cytolytic pathways, cytokine release, and Fas/FasL axis. In this review, we highlight the different tumor markers targeted for therapy against multiple myeloma (MM). Target antigens for CAR T cell therapy include B-cell maturation antigen (BCMA), signaling lymphocyte activation molecule F7 (SLAMF7), CD38, CD138, CD19, immunoglobulin kappa light chain, orphan G protein-coupled receptor class C group 5 member D (GPRC5D). With the benefit of improving survival and prognosis, this therapy does carry a risk of some adverse events such as cytokine release syndrome, encephalopathy, infections, hypogammaglobulinemia, and tumor lysis syndrome.

Formulation development and evaluation of zolmitriptan oral soluble films using 22 factorial designs.

OBJECTIVE: The present investigation involves the development of zolmitriptan oral soluble film (OSF) formulations and optimization with quality by design (QBD) using natural polymers and evaluation. MATERIALS AND METHODS: Initially, various natural polymers such as sodium alginate, pectin, and gelatin were screened by casting films using solvent casting technique and the prepared films were evaluated. Based on the physical and mechanical properties, sodium alginate was selected as best film former and zolmitriptan-loaded films were casted. The formulation was optimized with the help of 22 factorial experimental designs (QBD) in which sodium alginate concentration and plasticizer concentrations were used as factors and at two levels. The drug-loaded films were evaluated for various mechanical, physicochemical properties, and in vitro drug release properties. Factor effects were interpreted by calculating the main factor effects and by plotting the interaction plots. RESULTS: Thickness of the films, disintegration time, and percent drug loading efficiency were in the range of 0.698 ± 0.13-1.318 ± 0.22 mm, 175 ± 3.1-280 ± 1.7 s, and 68.34 ± 0.5-94.70 ± 0.7% w/v, respectively. Cumulative percent drug released was 61.8 ± 2.6-94.7 ± 4.1% after 30 min. Polymer concentration at two levels of plasticizer had statistically significant effect on drug loading efficiency and in vitro drug release rate. X2 formulation was found to be excellent in drug loading efficiency and in vitro drug release profiles; hence, drug excipient compatibility studies using Fourier transform infrared spectroscopy and stability studies for 60 days were carried out for X2 formulation and found to be stable. CONCLUSION: Sodium alginate OSFs containing zolmitriptan was successfully prepared, optimized, and evaluated.