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• Lipid mediated nanostructured lipid carriers, a delivery platform for active plant constituents. • Overcome two potent active plant constituent's solubility/permeability related issues. • Development of Compritol® 888 ATO (solid lipid), and squalene (liquid lipid) based lipid matrix. • Amorphous conversion of active plant constituents after encapsulation inside the lipid matrix. • Safety of NLCs was evidenced through no haemolysis in blood samples. Active plant constituents obtained from edible sources have manifested their pharmacological potential as a therapy against several diseases. But the lack of their desired physicochemical properties such as solubility, permeability ultimately leads to poor bioavailability. Two potent active plant constituents namely, quercetin and piperine having a problem with either solubility or permeability or both, and hence require an advanced lipid-mediated separate formulation system to improve their aforementioned concerns. Concerning advancement in nanoformulations, lipid-based nano-carriers systems have created their mark as a novel drug delivery system. Therefore, an advanced formulation like nanostructured lipid carriers (NLCs) has been formulated individually for both the active plant constituents/drugs through the solvent evaporation technique using high shear homogenization method followed by sonication. Compritol® 888 ATO, a solid lipid, and squalene as liquid lipid was used in their optimized ratios to formulate individual NLCs. Blank and individual drugs loaded NLCs were further characterized for their in vitro physicochemical properties. NLCs showed a negative surface charge with an average particle size below 200 nm. Electron microscopy images showed an anomalous structure of both the formulated NLCs with higher % drug encapsulation efficiency (DEE) with the desired in vitro drug release profile. In the case of quercetin-NLCs, 93.18 ± 5.5 % DEE was observed followed by drug release up to 45.0 ± 1.3 % within 12 h, while piperine-NLCs showed 91.80 ± 2.51 % DEE and drug release up to 38 ± 5.2 % at the same time. XRD and DSC plots showed the conversion of both the drugs into an amorphous structure encapsulated in a lyophilized NLCs matrix. Finally, the safety profile for formulated NLCs was confirmed by haemolysis assay. Hence, the developed active plant constituents enriched NLCs can further be delivered separately and/or in combination, and also may further be evaluated both in vitro and in vivo means. [ABSTRACT FROM AUTHOR]

• Validated analytical method was used for the simultaneous detection of quercetin and piperine by RP-HPLC. • The reported method is simple, fast, reliable and economic. • The method was successfully applied to quantify % DEE, % DL and in vitro cumulative % drug release study in NLCs. • This validated analytical method may further be applied for both the drugs in other lipid based nanoformulations. Quercetin and piperine are often used as an add-on therapy for various diseases, however both drug exhibits poor aqueous solubility and photosensitivity issue. Therefore, the aim of the present study is to improve the pharmaceutical challenges by incorporating both the drugs in nanostructured lipid carriers (NLCs) and to develop a sensitive, selective, accurate and precise reverse-phase high performance liquid chromatography (RP-HPLC) method for the simultaneous analysis of both drugs in NLCs. Effective chromatographic separation of quercetin and piperine was achieved on Hypersil gold C-18 column and mobile phase consisting of a mixture of acetonitrile and HPLC grade water (pH 2.6, adjusted with 2%v/v glacial acetic acid) in an isocratic elution mode. The flow rate of the mobile phase was 1 mL/min, column temperature at 35 ± 0.2 °C and the injection volume was 20 μL. The retention time for quercetin and piperine were found to be at 2.80 min and 10.36 min, respectively and detected at an isobestic wavelength of 346 nm using a photodiode array (PDA) detector. The method was found to be specific for the simultaneous analysis of quercetin and piperine in presence of NLCs matrix, accurate (>90%) and precise (%RSD < 2%). The validated RP-HPLC method effectively utilised to determine the percentage drug entrapment efficiency cum percentage drug loading of quercetin and piperine in NLCs enriched formulations along with the secondary estimation of in vitro cumulative percentage drug release study. The results were found to be reliable, hence the validated RP-HPLC method could be further used for the simultaneous detection and quantification of both these drugs in other lipid-based nano-formulations such as solid-lipid nanoparticles, polymer-lipid hybrid nanoparticles, lipid drug conjugates, etc. in in vitro and in vivo. [ABSTRACT FROM AUTHOR]

In last two decades, the lipid nanocarriers have been extensively investigated for their drug targeting efficiency towards the critical areas of the human body like CNS, cardiac region, tumor cells, etc. Owing to the flexibility and biocompatibility, the lipid-based nanocarriers, including nanoemulsion, liposomes, SLN, NLC etc. have gained much attention among various other nanocarrier systems for brain targeting of bioactives. Across different lipid nanocarriers, NLC remains to be the safest, stable, biocompatible and cost-effective drug carrier system with high encapsulation efficiency. Drug delivery to the brain always remains a challenging issue for scientists due to the complex structure and various barrier mechanisms surrounding the brain. The application of a suitable nanocarrier system and the use of any alternative route of drug administration like nose-to-brain drug delivery could overcome the hurdle and improves the therapeutic efficiency of CNS acting drugs thereof. NLC, a second-generation lipid nanocarrier, upsurges the drug permeation across the BBB due to its unique structural properties. The biocompatible lipid matrix and nano-size make it an ideal drug carrier for brain targeting. It offers many advantages over other drug carrier systems, including ease of manufacturing and scale-up to industrial level, higher drug targeting, high drug loading, control drug release, compatibility with a wide range of drug substances, non-toxic and non-irritant behavior. This review highlights recent progresses towards the development of NLC for brain targeting of bioactives with particular reference to its surface modifications, formulations aspects, pharmacokinetic behavior and efficacy towards the treatment of various neurological disorders like AD, PD, schizophrenia, epilepsy, brain cancer, CNS infection (viral and fungal), multiple sclerosis, cerebral ischemia, and cerebral malaria. This work describes in detail the role and application of NLC, along with its different fabrication techniques and associated limitations. Specific emphasis is given to compile a summary and graphical data on the area explored by scientists and researchers worldwide towards the treatment of neurological disorders with or without NLC. The article also highlights a brief insight into two prime approaches for brain targeting, including drug delivery across BBB and direct nose-to-brain drug delivery along with the current global status of specific neurological disorders. Unlabelled Image • Current global status of different neurological disorders and available therapies. • Different approaches of brain targeting including delivery across BBB and through intranasal route • Advantages and limitations of NLC along with various fabrication techniques • Complete research data of past decade explaining application of NLC for brain targeting of bioactives. • Pharmacokinetic data and preclinical progress of NLC based therapies towards treatment of CNS disorders [ABSTRACT FROM AUTHOR]

Oral squamous cellular carcinoma (OSCC) is considered a life-threatening disease with detection in late stages, which forces us to opt for dangerous treatment with a combination of chemotherapy and radiotherapy. Herbal components such as piperine and quercetin are derived from edible sources, proving their anticancer potential against oral cancer cells in vitro. Encapsulation into lipid matrix-mediated nanostructured lipid carriers (NLCs) can make both drugs bio-accessible. NLCs were synthesised using the high shear homogenisation method and characterised for their physicochemical properties, followed by in vitro cellular evaluation in FaDu oral cancer cells. NLCs showed negatively charged particles smaller than 180 nm with a polydispersity index (PDI) of <0.3. Both drugs were found to encapsulate sufficiently, with >85% entrapment efficiency and an improved drug release profile compared to their pristine counterparts. Differential scanning calorimetry (DSC) thermograms showed conversion into an amorphous matrix in lyophilized NLCs, which was supported by X-ray diffraction (XRD) analysis. The cytotoxicity assay showed the IC 50 concentration for dual drug-loaded NLCs, which was more effective than the pure drug solution. NLCs were found to be internalised in cells in a short time with an almost 95% co-localization rate. Dual drug-loaded NLCs showed maximum depolarisation of the mitochondrial membrane along with more apoptotic changes. Improved apoptosis was confirmed in NLCs using flow cytometry. The in vivo biodistribution of Coumarin-6 labelled NLCs in rats confirmed their efficient distribution in various parts of the oral cavity through oral administration. Optimised dual drug-loaded NLCs provide a better option for delivering both drugs through a single lipid matrix against oral cancer. [Display omitted] [ABSTRACT FROM AUTHOR]