DEVELOPMENT AND CHARACTERIZATION OF DOXORUBICIN AND siRNA ENCAPSULATED CHITOSAN NANOPARTICLES

Objective: Chitosan nanoparticles (ChNP’s) have been widely studied for drug and gene delivery. In this study, we prepared ChNP’s for co-delivery of doxorubicin (DOX) and siRNA for cancer treatment. Methods: The ionic gelation method was used to develop ChNP’s. The positively charged DOX and negatively charged siRNA encapsulated into ChNP’s. The particle size and zeta potential of the developed ChNP’s were studied by particle size analyzer and morphology was examined by TEM. Encapsulation of DOX in ChNP’s was confirmed by FTIR spectroscopy. The encapsulation efficiency and in vitro release of DOX were studied by UV-Vis spectrophotometry. The siRNA loading into ChNP’s was confirmed by gel retardation assay. Results: The developed ChNP’s showed particle size ranged from 127±6.5 to 215±8.5 nm with zeta potential ranged from 16.5±0.3 to 25.8±0.3. Transmission Electron Micrograph showed DOX and siRNA encapsulated ChNP’s are polydisperse and spherical in nature. FTIR study confirmed the binding of DOX with ChNP’s with absorption peaks at 1016 cm-1, 1316 cm-1, 1412 cm-1, 1645 cm-1 and 3370 cm-1. The TPP:Ch ratio 0.1:0.5 showed the highest encapsulation efficiency 69±3.24%, with initial burst release and then sustained or slow release of DOX. Agarose gel retardation study confirmed the encapsulation of siRNA in ChNP’s by retarded migration of siRNA-ChNP’s in comparison with naked siRNA. Conclusion: The developed ChNP’s successfully encapsulated the DOX and siRNA and showed the sustain release of DOX. In conclusion, our study shown that ChNP’s is having a potential of co-loading of DOX-siRNA as an efficient drug delivery system for the treatment of various cancers such as colorectal cancer, breast cancer etc

TAILORING THE NANOPARTICLES SURFACE FOR EFFICIENT CANCER THERAPEUTICS DELIVERY

Nanotechnology has tremendous advantages in many areas of scientific as well as clinical research. The development of nanoparticles (NPs) that can efficiently deliver drugs specifically to the cancer cells can help reduce normal cells toxicity and co-morbidities. Cancer can be treated by exploiting the unique physiochemical of the NPs, and modulating their surface modifications using ligands which further could be used as drug cargo vehicles. To enhance biocompatibility and drug delivery towards the target site, various modifications can be included to modify the surface of the NPs, such as carbohydrates, dendrimers, DNA, RNA, siRNA, drugs, and other ligands. These ligand-coated NPs have potential applications in the field of biomedical research, including diagnosis, contrast agents for molecular and clinical imaging (Magnetic Resonance Imaging (MRI), Computed tomography (CT), positron emission tomography (PET)), as cargo vehicles for drugs, increasing the blood circulation half-life, and blood detoxification. Further, the conjugation of anti-cancer drugs to the NPs can be efficiently used to target the cancer disease. This review highlights some of the features and surface modification strategies of the NPs, such as an iron oxide (IO), liposomes (LP)-based NPs, and polymer-based NPs, which show their effectiveness as cargo agents for cancer therapeutics

IN LABORATORY GENERATION AND MATURATION OF HUMAN MONOCYTE-DERIVED DENDRITIC CELLS FOR CANCER IMMUNOTHERAPY

Dendritic cells (DCs) play a critical role in the regulation of adaptive immune responses, furthermore they act as a bridge between the innate and the adaptive immune systems they have been ideal candidates for cell-based immunotherapy of cancers and infections in humans. The first reported trial using DCs in 1995, since they have been used in trials all over the world for several of indications, including cancer and human immunodeficiency virus infection. Generally, for in vitro experiments or for DCs vaccination monocyte-derived dendritic cells (moDCs) were generated from purified monocytes that isolated from peripheral blood by density gradient centrifugation. A variety of methods can be used for enrichment of monocytes for generation of clinical-grade DCs. Herein we summarized up to date understanding of systems and inputs used in procedures to differentiate DCs from blood monocytes in vitro

Recent trends in siRNA delivery for treatment of colorectal cancer: siRNA delivery for treatment of colorectal cancer

Colorectal cancer (CRC) is the third most widespread cancer in the world. Currently, chemotherapy is effective treatment for CRC. Major problem with chemotherapy is the acquired multi drug resistance (MDR). Recently, siRNA (small interfering RNA) therapeutics has getting more attention to overcome the MDR in cancer and in various diseases. siRNA is a 21-23 base pair double stranded RNA having ability to silence specific genes at post transcriptional level. But, clinical practice of siRNA delivery having limitation due to enzymatic degradation by serum nucleases resulting poor stability, poor cellular uptake at target site. Now a days, development of various nanocarriers for efficient delivery of siRNA is a most challenging and rapidly growing research area. In this review, we summarize, the potential of various nanocarriers such as polymeric nanoparticles, lipid-based nanoparticles, inorganic nanoparticles, layered double hydroxide nanoparticles for siRNA delivery in colorectal cancer treatment

THE ROLE OF CARBON NANOTUBES IN NANOBIOMEDICINES

CNTs is a fullerene molecule, described in 1991 by the Japanese Scientist ‘‘Sumio Iijima'' as tube-shaped of graphitic carbon, can be obtained either single or multi-walled nanotube, having a diameter measuring on the nanometer scale, and generally known as buckytubes. Carbon nanotubes (CNTs) have established much recent interest as new entities for experimental disease diagnosis and treatment because of their unique electronic, mechanical, thermal, spectroscopic, metallic, semiconducting and superconducting electron transport properties. Carbon nanotubes can be acquired in numerous ways, the general techniques are Arc discharge, Laser ablation, and Chemical vapour deposition (CVD). Carbon nanotubes are discussed in this review in terms of characters, history, structures, properties, synthesis, purification, characterization methods, toxicity and applications. Purification of nanotubes includes many techniques: Acid treatment, oxidation, annealing, ultrasonication, cutting, magnetic purification, chromatography techniques. Further functionalization enhanced the water solubility of CNT's and completely transformed their biocompatibility profile. Carbon nanotubes, due to their large surface areas, unique surface properties, and needle-like shape, can deliver a lot of therapeutic agents, including DNA, siRNAs and proteins to the target disease sites. CNTs can be readily excreted through the renal route by means of degradation through myeloperoxidase (MOP) enzyme. As CNTs have attracted the fancy of many scientists worldwide, the work beyond our expectations and their simple mechanism with long lasting life makes it more reliable to use. The unique and unusual properties of these structures make them a unique material with a whole range of promising applications

MANNOSYLATED MULTIWALLED CARBON NANOTUBES ASSISTED ARTESUNATE DELIVERY FOR CEREBRAL MALARIA: MULTIWALLED CARBON NANOTUBES ASSISTED ARTESUNATE DELIVERY

Objective: The present investigation focused on the novel approach using artesunate (AS) loaded mannosylated conjugated multi-walled carbon nanotubes (M-MWCNTs) for site-specific delivery to the brain in the treatment of cerebral malaria (CM). Methods: The raw MWCNTs were purified by selective oxidation method and then exposed to sequential chemical functionalization according to the following steps: carboxylation, acylation, amine modification and finally, D-mannose conjugation. The AS was loaded via the equilibrium dialysis method in the molar ratio 1:3 of various functionalized sonicated MWCNTs. The functionalized MWCNTs were characterized for elemental analysis, FTIR, TEM, zeta potential and percentage drug entrapment efficiency. The in vitro drug release study was performed on AS conjugated purified MWCNTs (AS-P-MWCNT) and AS conjugated M-MWCNTs. Bio-distribution study was performed on albino rat for quantitative measurement of AS in different organs and blood. Results: The TEM images of M-MWCNTs indicated their open tubular nature and AS-M-MWCNTs suggests the entrapment of AS. The percent drug entrapment of AS-M-MWCNT was found to be 80.29±3.4 %. In vitro AS release from AS-M-MWCNTs was found in a controlled manner at pH 7.4. The bio-distribution studies clearly indicate the superiority of the AS-M-MWCNTs, as compared to the plain drug towards increasing the accumulation of AS in brain. Conclusion: The results suggest that AS-M-MWCNTs could be employed as an efficient nano-carrier for antimalarial therapy in cerebral malaria

QbD-driven RP-HPLC method for novel chemo-herbal combination, in-silico, force degradation studies, and characterization of dual drug-loaded polymeric and lipidic nanocarriers

Abstract Background In cancer therapies, chemo-herbal combinations are receiving increased attention. A multiple tyrosine kinase inhibitor, lenvatinib (LTB) is beneficial in treating thyroid, lung, endometrial, and liver cancers. An isoflavone called biochanin A (BCA) is well known for its diverse biological properties that have been studied to potentiate the anti-cancer potential and lower the normal cell toxicities of other therapeutics. LTB and BCA can be combined for cancer treatment and may increase their therapeutic potential at lower doses. In brief, the quality by design (QbD)-driven RP-HPLC method was developed, validated, and utilized for applications employing the study of forced degradants and the successful development of LTB and BCA co-loaded nanocarriers. Results The RP-HPLC method employed Box–Behnken design with peak resolution 6.70 ± 0.006, tailing factor 1.06 ± 0.05 for BCA and 1.17 ± 0.021 for LTB, and theoretical plates number > 2000. RP-HPLC applications utilized the investigation of a total of 41.17% and 70.58% degradants for LTB and BCA in contrast to in-silico predicted studies using Zeneth software. The poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) were formed with particle size 185.3 ± 12.3 nm, zeta potential − 13.3 ± 0.35 mV, and percentage entrapment efficiency (%EE) for the LTB and BCA 53.64 ± 4.81% and 61.29 ± 4.67%, respectively. However, the developed Cubosomes (CBs) exhibited 182.4 ± 16.3 nm aerodynamic particle size, − 10.8 ± 0.39 mV zeta potential, and % EE for LTB and BCA 55.62 ± 7.73% and 72.88 ± 5.52%, respectively. The percentage drug loading (%DL) of LTB and BCA from PLGA NPs was found to be 3.7 ± 0.46% and 4.63 ± 0.48%, whereas CBs exhibited higher % DL for BCA (5.42 ± 1.10%) and LTB (4.43 ± 0.77%). Conclusion The RP-HPLC method was developed and validated according to ICH and USP guidelines. In-vitro and in-silico forced degradation studies are evident to quantify the type of degradant and its exact mechanism of degradation. In-silico toxicity assessment for LTB, BCA, and their degradants explains the necessity of conducting degradation studies during drug development. Finally, the applications of the developed RP-HPLC method explain the usefulness of analytical methods in the development of chemo-herbal drug nanocarriers (polymeric and lipidic). Graphical abstrac

COVID-19 vaccines: rapid development, implications, challenges and future prospects

COVID-19 has affected millions of people and put an unparalleled burden on healthcare systems as well as economies throughout the world. Currently, there is no decisive therapy for COVID-19 or related complications. The only hope to mitigate this pandemic is through vaccines. The COVID-19 vaccines are being developed rapidly, compared to traditional vaccines, and are being approved via Emergency Use Authorization (EUA) worldwide. So far, there are 232 vaccine candidates. One hundred and seventy-two are in preclinical development and 60 in clinical development, of which 9 are approved under EUA by different countries. This includes the United Kingdom (UK), United States of America (USA), Canada, Russia, China, and India. Distributing vaccination to all, with a safe and efficacious vaccine is the leading priority for all nations to combat this COVID-19 pandemic. However, the current accelerated process of COVID-19 vaccine development and EUA has many unanswered questions. In addition, the change in strain of SARS-CoV-2 in UK and South Africa, and its increasing spread across the world have raised more challenges, both for the vaccine developers as well as the governments across the world. In this review, we have discussed the different type of vaccines with examples of COVID-19 vaccines, their rapid development compared to the traditional vaccine, associated challenges, and future prospects