This study supports a significant role for QMNE in terms of high brain-targeting potential and formulation efficiency due to ease of access and effective targeting in brain.

Chemotherapeutic delivery by oral route in cancer patients has the potential to create "hospitalization free chemotherapy" which is a vision of oncologists, formulation scientists and patients. Such a therapeutic approach will improve patients' compliance, ease the burden of the patients' caregivers and significantly reduce the cost of treatment. In current clinical practice, chemotherapy carried out by intravenous injection or infusion leads to undesired side-effects such as plasma concentrations crossing the maximum safe concentration, rapid body clearance and lower bioavailability. Despite the presence of challenges such as poor aqueous solubility and stability of drugs and the presence of biological barriers like multidrug efflux transporter in the GI tract, oral cancer chemotherapy has the potential to surmount those obstacles. Lipid nanoparticles (LNPs) such as solid lipid nanoparticle, nanostructured lipid carriers, nano lipid-drug conjugates, mixed micelles, liposomes and nanoemulsions have shown some promising results for use in oral anticancer drug delivery through nanotechnological approach. LNPs demonstrate enhanced oral bioavailability owing to their ability to inhibit first pass metabolism via lymphatic absorption by chylomicron-linked and/or M-cell uptake. LNPs reduce the inter- and intrasubject pharmacokinetics variability of administrated drugs. Moreover, certain classes of phospholipids and surfactants used in the formulations of LNPs can suppress the P-glycoprotein efflux system. Here, we shall be discussing the biopharmaceutical challenges in oral cancer chemotherapy and how the LNPs may provide solutions to such challenges. The effect of GI tract environment on LNPs and pharmacokinetics shall also be discussed.

Background: Glycyrrhizic Acid (GRA), a potent antioxidant triterpene saponin glycoside and neuroprotective properties exhibits an important role in the treatment of neurological disorders i.e. cerebral ischemia. GRA is water soluble, therefore it’s have low bioavailability in the brain. Objective: To enhance brain bioavailability for intranasally administered Glycyrrhizic Acidencapsulated- chitosan-coated-PCL-Nanoparticles (CS-GRA-PCL-NPs). Methods: Chitosan-coated-PCL-Nanoparticles (CS-PCL-NPs) were developed through double emulsification- solvent evaporation technique and further characterized for particle size, zeta potential, size distribution, encapsulation efficiency as well as in vitro drug release. UPLC triple quadrupole Qtrap MS/MS method was developed to evaluate brain-drug uptake for optimized CS-GRA-PCL-NPs and to determine its pharmacokinetic in rat’s brain as well as plasma. Results: Mean particles size (231.47±7.82), polydispersity index (PDI) i.e. (0.216±0.030) and entrapment efficiency (65.69±5.68) was determined for developed NPs. UPLC triple quadrupole Qtrap MS/MS method study showed a significantly high mucoadhesive potential of CS-GRA-PCL-NPs and least for conventional and homogenized nanoformulation; elution time for GRA and internal standard (IS) Hydrocortisone as 0.37 and 1.94 min at m/z 821.49/113.41 and 363.45/121.40 were observed, respectively. Furthermore, intra and inter-assay (%CV) of 0.49-5.48, %accuracy (90.00-99.09%) as well as a linear dynamic range (10.00 ng/mL -2000.0 ng/mL), was observed. Pharmacokinetic studies in Wistar rat brain exhibited a high AUC0-24 alongwith an amplified Cmax (p** < 0.01) as compared to i.v. treated group. Conclusion: Intranasal administration of developed CS-coated-GRA-loaded-PCL-NPs enhanced the drug bioavailability in rat brain along with successfully UPLC-MS/MS method and thus preparation of GRA-NPs may help treat cerebral ischemia effectively. The toxicity studies performed at the end revealed safe nature of optimized nanoformulation.

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Quercetin (Qur) and its major in vivo bioactive metabolites i. e., 3'--methyl quercetin, 4'--methyl quercetin and quercetin 7---D-glucuronide, may be used to treat cerebral ischemia however the poor aqueous solubility and less intestinal absorption of Qur results low bioavailability. To improve Qur bioavailability through preparation of nanoformulation and to develop and validate a sensitive quantification method for Qur detection in brain homogenate. Qur-containing self-nanoemulsifying drug delivery system (Qur-SNEDDS) was developed to form oil-in-water nanoemulsions in situ. Ultra-high performance liquid chromatography electrospray ionization-synapt mass spectrometric method (UHPLC/ESI-QTOF-MS/MS) was developed and validated for quantification whereas for optimal recovery of analyte, a liquid-liquid extraction method (LLE) was used. A droplet size of 94.63±3.17 nm and zeta potential of -17.91±1.02 mV for nanoemuslion, elution time for Qur and internal standard (IS) Rutin as 1.21 and 1.50 min alongwith a transition at m/z 301.04/151.03 and 609.21/299.21, were observed respectively. Similarly, linear dynamic range (1.00 ng/mL-2 000.0 ng/mL), intra and inter-assay i. e., %CV of 0.26-2.04, lower limit of detection (LOD) 0.08 ng/mL as well as lower limit of quantitation (LOQ) as 0.131 ng/mL were also observed. The developed method have advantage over previous all methods i. e., less time consuming (<3.0), low consumption of solvents (flow rate 0.20 mL/min.) via small size column, more accuracy and specificity as well as use of acetonitrile as compared to hazardous solvents. This certainly adds advantages for green chromatography technique and supports application of current developed method for quantification and evaluation of Qur-SNEDDS.