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Multi-drug resistance has shown to be one of the leading threats faced currently in many chemotherapeutic agents. Permeability glycoprotein (P-gp) is an efflux transporter in membrane, an integral part of ATP-binding cassette (ABC) transporters widely distributed in the body for cellular uptake. It is present enormously in cancerous cells and is in charge of generating transporter mediated resistance to treatments of tumorous cells in addition to blocking the entry of chemotherapeutic drugs into the cell. Natural P-gp inhibitors are derived from natural plant sources possessing basic structures like alkaloids, flavonoids, phenolics, terpenoids, saponins, sapogenins, sterols, coumarins and miscellaneous structures acting on P-gp substrate for inhibition of multi-drug resistance via inhibiting the efflux pump. They do not depict their action on the healthy cells and thus it is proven to be more effective and less toxic than synthetic P-gp inhibitor leading to enhancement in bioavailability of chemotherapeutic drugs. The significant objective of the present review is surfing through the impact of natural P-gp inhibitors having basic structures derived from the plant sources and how it inhibits the resistance of chemotherapeutic drugs together with how well it delivers chemotherapy medicines. [ABSTRACT FROM AUTHOR]

Targeted delivery of therapeutics forestalls the dreadful delocalized effects, drug toxicities and needless immunosuppression. Cancer cells are bounteous with sialic acid and the differential expression of glycosyl transferase, glycosidase and monosaccharide transporter compared to healthy tissues. The current study entails the development and characterisation of sialic acid (SA)–labelled chitosan nanoparticles encapsulating gemcitabine (GEM). Chitosan (CS) was conjugated with SA using coupling reaction and characterised spectroscopically. Furthermore, different concentrations of chitosan and tripolyphosphate (TPP) were optimised to fabricate surface modified chitosan nanoparticles. SA conjugated chitosan nanoparticles encapsulating GEM (SA-CS_GEM NPs) of 232 ± 9.69 nm with narrow distribution (PDI < 0.5) and zeta potential of − 19 ± 0.97 mV was fabricated. GEM was successfully loaded in the SA-CS NPs, depicting prolonged and biphasic drug release pattern more elated at low pH. Pronounced cellular uptake (FITC tagged) and cytotoxicity (IC50 487.4 nM) was observed in SA-CS_GEM NPs against A549 cells. IC50 for SA-CS_GEM NPs plunged with an increase in the time points from 24 to 72 h. Concentration-dependent haemolytic study confirmed significant haemocompatibility of SA-CS_GEM NPs. Pharmacokinetic study was performed on Sprague–Dawley rats and the kinetic parameters were calculated using PKSolver 2.0. Results demonstrated a consequential refinement of 2.98 times in modified SA-CS_GEM NPs with a significant increase in retention time, bioavailability and elimination half-life, and decrease in elimination rate constant and volume of distribution in comparison to CS_GEM NPs. Therefore, SA-CS shell core nanoparticles could be a beneficial approach to target and treat NSCLC (non-small cell lung cancer) and direct for research possibilities to target the other tumour cells. [ABSTRACT FROM AUTHOR]

Abstract: Globally, the central nervous system (CNS) disorders appear as the most critical pathological threat with no proper cure. Alzheimer's disease (AD) is one such condition frequently observed with the aged population and sometimes in youth too. Most of the research utilizes different animal models for in vivo study of AD pathophysiology and to investigate the potency of the newly developed therapy. These in vivo models undoubtably provide a powerful investigation tool to study human brain. Although, it sometime fails to mimic the exact environment and responses as the human brain owing to the distinctive genetic and anatomical features of human and rodent brain. In such condition, the in vitro cell model derived from patient specific cell or human cell lines can recapitulate the human brain environment. In addition, the frequent use of animals in research increases the cost of study and creates various ethical issues. Instead, the use of in vitro cellular models along with animal models can enhance the translational values of in vivo models and represent a better and effective mean to investigate the potency of therapeutics. This strategy also limits the excessive use of laboratory animal during the drug development process. Generally, the in vitro cell lines are cultured from AD rat brain endothelial cells, the rodent models, human astrocytes, human brain capillary endothelial cells, patient derived iPSCs (induced pluripotent stem cells) and also from the non-neuronal cells. During the literature review process, we observed that there are very few reviews available which describe the significance and characteristics of in vitro cell lines, for AD investigation. Thus, in the present review article, we have compiled the various in vitro cell lines used in AD investigation including HBMEC, BCECs, SHSY-5Y, hCMEC/D3, PC-2 cell line, bEND3 cells, HEK293, hNPCs, RBE4 cells, SK-N-MC, BMVECs, CALU-3, 7W CHO, iPSCs and cerebral organoids cell lines and different types of culture media such as SCM, EMEM, DMEM/F12, RPMI, EBM and 3D-cell culture.Graphical Abstract: [ABSTRACT FROM AUTHOR]

A novel diclofenac sodium (DS) loaded interpenetrating polymer network (IPN) beads of pectin and hydrolyzed polyacrylamide-graft-sodium alginate (PAAm-g-SA) was developed through ionotropic gelation and covalent cross-linking. The graft copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The grafting, alkaline hydrolysis, and characterization of beads were confirmed by Fourier transforms infrared spectroscopy. The crystalline structure of drug after encapsulation into IPN beads were evaluated by differential scanning colorimetry and X-ray diffraction analyses. DS encapsulation was up to 96.45 %. The effect of hydrolyzed graft copolymer/pectin ratios and glutaraldehyde concentration on drug release in acidic and phosphate buffer solutions were investigated. The release of drug was significantly increased with increase of pH. The release of drug depends on the extent of cross-linking. The results indicated that IPN beads of hydrolyzed PAAm-g-SA and pectin could be used for sustained release of DS. [ABSTRACT FROM AUTHOR]

Purpose: Combinatorial approach can be beneficial for cancer treatment with better patient recovery. Co-delivery of natural and synthetic anticancer drug not only valuable to achieve better anticancer effectivity but also to ascertain toxicity. This study was aimed to co-deliver berberine (natural origin) and doxorubicin (synthetic origin) utilizing conjugation/encapsulation strategy through poly (lactic-co-glycolic acid) (PLGA) nanoparticles. Methods: Doxorubicin was efficiently conjugated to PLGA via carbodiimide chemistry and the PLGA-doxorubicin conjugate (PDC) was used for encapsulation of berberine (PDBNP). Results: Significant anti-proliferative against MDA-MB-231 and T47D breast cancer cell lines were observed with IC50 of 1.94 ± 0.22 and 1.02 ± 0.36 μM, which was significantly better than both the bio-actives (p < 0.05). The ROS study revealed that the PDBNP portrayed the slight increase in the reactive oxygen species (ROS) pattern in MDA-MB-231 cell line in a dose-dependent manner, while in T47D cells, no significant change in ROS was seen. PDBNP exhibits significant alteration (depolarization) in mitochondrial membrane permeability and arrest of cell cycle progression at sub G1 phase while the Annexin V/PI assay followed by confocal microscopy resulted into cell death mode to be because of necrosis against MDA-MB-231 cells. In vivo studies in Sprague Dawley rats revealed almost 14-fold increase in half life and a significant increase in plasma drug concentration. Conclusion: The overall approach of PLGA based co-delivery of doxorubicin and berberine witnessed synergetic effect and reduced toxicity as evidenced by preliminary toxicity studies. [ABSTRACT FROM AUTHOR]