Quality by design-steered development and validation of analytical and bioanalytical methods for raloxifene: Application of Monte Carlo simulations and variance inflation factor.

A sensitive, rapid, reproducible, and economical HPLC method is reported for the quantification of raloxifene hydrochloride employing Quality by Design (QbD) principles. Factor screening studies, employing Taguchi design, indicated buffer volume percentage and isocratic flow rate as the critical method parameters (CMPs), which significantly influence the chosen critical analytical attributes, that is, tailing factor and theoretical plate number. Method conditions were subsequently optimized using face-centered cubic design with magnitude of variance inflation factor for assessing multicollinearity among CMPs. Method operable design region (MODR) was earmarked and liquid chromatographic separation optimized using 0.05 M citrate buffer, acetonitrile, and methanol (57:40:3 v/v/v) as ggmobile phase at 0.9 mL min-1 flow rate, λmax of 280 nm, and column temperature of 40°C. Validation of the developed analytical method was accomplished as per International Council on Harmonization (ICH) guidelines confirming high levels of linearity, precision, accuracy, robustness, and sensitivity. Application of Monte Carlo simulations enabled the attainment of best plausible chromatographic resolution and corroboration of the demarcated MODR. Establishment and validation of the bioanalytical method using rat plasma samples, along with forced degradation and stability studies, corroborated the aptness of developed HPLC methods for drug quantification in the biological fluids, as well as in bulk and marketed dosage forms.

QbD-driven development and evaluation of nanostructured lipid carriers (NLCs) of Olmesartan medoxomil employing multivariate statistical techniques.

PURPOSE: This research work entails quality by design (QbD)-based systematic development of nanostructured lipid carriers (NLCs) of Olmesartan medoxomil (OLM) with improved biopharmaceutical attributes. METHODS: Quality target product profile (QTPP) was defined and critical quality attributes (CQAs) were earmarked. Solubility of drug was performed in various lipids for screening of them. NLCs were prepared by hot-microemulsion method using solid lipids, liquid lipids and surfactants with maximal solubility. Failure mode and effect analysis (FMEA) was carried out for identifying high risk formulation and process parameters. Further, principal component analysis (PCA) was applied on high risk parameters for evaluating the effect of type and concentration of lipids and surfactants on CQAs. Further, systematic optimization of critical material attributes (CMAs) was carried out using face centered cubic design and optimized formulation was identified in the design space. RESULTS: FMEA and PCA suggested suitability of stearic acid, oleic acid and Tween 80 as the CMAs for NLCs. Response surface optimization helped in identifying the optimized NLC formulation with particle size ∼250 nm, zeta potential <25 mV, entrapment efficiency >75%, in vitro drug release >80% within 6 h. Release kinetic modeling indicated drug release through Fickian-diffusion mechanism. CONCLUSIONS: Overall, these studies indicated successful development of NLCs using multivariate statistical approaches for improved product and process understanding.

QbD-driven development of phospholipid-embedded lipidic nanocarriers of raloxifene: extensive in vitro and in vivo evaluation studies.

Raloxifene (RLX) is popularly indicated in treatment of osteoporosis and prevention of breast cancer. Owing to its poor aqueous solubility, high pre-systemic metabolism, intestinal glucuronidation, and P-glycoprotein (P-gp) efflux, however, it demonstrates low (< 2%) and inconsistent oral bioavailability. The current work, Quality by Design (QbD)-driven development of phospholipid-embedded nanostructured lipidic carriers (NLCs) of RLX, accordingly, was undertaken to potentiate its lymphatic uptake, augment oral bioavailability, and possibly reduce drug dosage. Factor screening and failure mode effect analysis (FMEA) studies were performed to delineate high-risk factors using solid lipid (glyceryl monostearate), liquid lipid (vitamin E), and surfactant (Tween 80). Response surface optimization studies were performed employing the Box-Behnken design. Mathematical and graphical methods were adopted to embark upon the selection of optimized NLCs with various critical quality attributes (CQAs) of mean particle size as 186 nm, zeta potential of - 23.6 mV, entrapment efficiency of 80.09%, and cumulative drug release at 12 h of 83.87%. The DSC and FTIR studies, conducted on optimized NLCs, indicated successful entrapment of drug into the lipid matrix. In vitro drug release studies demonstrated Fickian diffusion mechanism. In vivo pharmacokinetic studies in rats construed significant improvement in AUC0-72 h (4.48-folds) and in Cmax (5.11-folds), unequivocally indicating markedly superior (p < 0.001) oral bioavailability of RLX-NLCs vis-à-vis marketed tablet formulation. Subsequently, level "A" in vitro/in vivo correlation (IVIVC) was also successfully attempted between the percentages of in vitro drug dissolved and of in vivo drug absorbed at the matching time points. In vitro cytotoxicity and cellular uptake studies also corroborated higher efficacy and successful localization of coumarin-6-loaded NLCs into MG-63 cells through microfluidic channels.

Chitosan modified 5-fluorouracil nanostructured lipid carriers for treatment of diabetic retinopathy in rats: A new dimension to an anticancer drug.

Diabetic retinopathy (DR) is one of the chronic complications of diabetes. It includes retinal blood vessels' damage. If untreated, it leads to loss of vision. The existing treatment strategies for DR are expensive, invasive, and need expertise during administration. Hence, there is a need to develop a non-invasive topical formulation that can penetrate deep to the posterior segment of retina and treat the damaged retinal vessels. In addition, it should also provide sustained release. In recent years, novel drug delivery systems (NDDS) have been explored for treating DR and found successful. In this study, chitosan (CS) modified 5-Fluorouracil Nanostructured Lipid Carriers (CS-5-FU-NLCs) were prepared by modified melt emulsification-ultrasonication method and optimized by Box-Behnken Design. The size, polydispersity index, zeta potential and entrapment efficiency of CS-5-FU-NLCs were 163.2 ± 2.3 nm, 0.28 ± 1.52, 21.4 ± 0.5 mV and 85.0 ± 0.2 %, respectively. The in vitro drug release and ex vivo permeation study confirmed higher and sustained drug release in CS-5-FU-NLCs as compared to 5-FU solution. HET-CAM Model ensured the non-irritant nature of CS-5-FU-NLCs. In vivo ocular studies of CS-5-FU-NLCs confirmed antiangiogenic effect of 5-FU by CAM model and diabetic retinopathy induced rat model, indicating successful delivery of 5-FU to the retina.

Multivariate Data Analysis and Central Composite Design-Oriented Optimization of Solid Carriers for Formulation of Curcumin-Loaded Solid SNEDDS: Dissolution and Bioavailability Assessment.

The study was initiated with two major purposes: investigating the role of isomalt (GIQ9) as a pharmaceutical carrier for solid self-nanoemulsifying drug delivery systems (S-SNEDDSs) and improving the oral bioavailability of lipophilic curcumin (CUN). GIQ9 has never been explored for solidification of liquid lipid-based nanoparticles such as a liquid isotropic mixture of a SNEDDS containing oil, surfactant and co-surfactant. The suitability of GIQ9 as a carrier was assessed by calculating the loading factor, flow and micromeritic properties. The S-SNEDDSs were prepared by surface adsorption technique. The formulation variables were optimized using central composite design (CCD). The optimized S-SNEDDS was evaluated for differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), microscopy, dissolution and pharmacokinetic studies. The S-SNEDDS showed a particle size, zeta potential and PDI of 97 nm, -26.8 mV and 0.354, respectively. The results of DSC, XRD, FTIR and microscopic studies revealed that the isotropic mixture was adsorbed onto the solid carrier. The L-SNEDDS and S-SNEDDS showed no significant difference in drug release, indicating no change upon solidification. The optimized S-SNEDDS showed 5.1-fold and 61.7-fold enhancement in dissolution rate and oral bioavailability as compared to the naïve curcumin. The overall outcomes of the study indicated the suitability of GIQ9 as a solid carrier for SNEDDSs.

Polymeric micelles loaded with glyburide and vanillic acid: I. Formulation development, in-vitro characterization and bioavailability studies.

The co-formulation of glyburide (Gly) and vanillic acid (VA) as such in the form of nanomedicine has never been explored to treat metabolic diseases including type 2 diabetes mellitus. Both the drugs possess dissolution rate-limited oral bioavailability leading to poor therapeutic efficacy. Hence, co-loading these drugs into a nanocarrier could overcome their poor oral bioavailability related challenges. Owing to this objective, both drugs were co-loaded in amphiphilic polymeric micelles (APMs) and evaluated for their biopharmaceutical outcomes. The APMs were prepared using mPEG-b-PCL/CTAB as a copolymer-surfactant system via the liquid antisolvent precipitation (LAP) method. The design of these APMs were optimized using Box Behnken Design by taking various process/formulation based variables to achieve the desired micellar traits. The release of both the drugs from the optimized co-loaded APMs was compared in different media and displayed a remarkable sustained release profile owing to their hydrophobic interactions with the PCL core. The in vitro cytotoxicity study of co-loaded APMs on Caco-2 cells revealed 70 % cell viability in a concentration-dependent manner. The preventive effects of Gly and VA co-loaded in APMs on glucose uptake was studied in insulin-responsive human HepG2 cells treated with high glucose. The co-loading of both the drugs in optimized APMs exhibited synergistic glucose-lowering activity (p < 0.001) than raw drugs with low cytotoxicity on HepG2 cells within the test concentration. This could be attributed to an increase in the relative oral bioavailability of both the drugs in APMs i.e., 868 % for Gly and 87 % for VA respectively.

Application of nanotechnology to herbal antioxidants as improved phytomedicine: An expanding horizon.

Phytotherapy, based on medicinal plants, have excellent potential in managing several diseases. A vital part of the healthcare system is herbal medicines, consisting of therapeutic agents with high safety profile and no or least adverse effects. Herbs or medicinal plants show anticancer, antioxidant, and gene-protective activity, which is useful for pharmaceutical industries. In vitro, the extract of antioxidant compounds prevents the growth of colon and liver cancer cells, followed by a dose-dependent method. The screening of extracts is done by using in vitro models. Reactive oxygen species (ROS) and free radicals lead to diseases based on age which promotes oxidative stress. Different types of ROSs available have central roles in the normal physiology and functioning of processes. Herbal or traditional plant medicines have rich antioxidant activity. Despite the limited literature on the health effect of herbal extract or spices. There are many studies examining the encouraging health effects of single phytochemicals instigating from the medicinal plant. This review provides a detailed overview on herbal antioxidants and how application of nanotechnology can improve its biological activity in managing several major diseases, and having no reported side effects.

Systematically designed chitosan-coated solid lipid nanoparticles of ferulic acid for effective management of Alzheimer's disease: A preclinical evidence.

Ferulic acid (FA) is a ubiquitous natural plant bioactive with distinctive promise in neurodegenerative disorders. However, its therapeutic efficacy gets compromised owing to its poor aqueous solubility, inadequate permeability across lipophilic barriers, and extensive first-pass metabolism. The current studies, therefore, were undertaken to systematically develop chitosan-coated solid lipid nanoparticles (SLNs) using QbD paradigms for improved efficacy of FA in the management of Alzheimer's disease (AD). SLNs of FA were formulated employing Compritol as lipid and polysorbate 80 as surfactant and optimised using a 32 Central Composite Design (CCD). The optimized formulation, surface-coated with chitosan using ionic gelation, exhibited particle size of 185 nm, entrapment efficiency of 51.2 % and zeta potential of 12.4 mV. FTIR and DSC studies verified the compatibility of FA with formulation excipients, PXRD construed significant loss of drug crystallinity, while FESEM depicted existence of uniform spherical nanoparticles with little aggregation. Notable improvement in ex vivo mucoadhesion and permeation studies using goat nasal mucosa, coupled with extension in in vitro drug release, was obtained with SLNs. Substantial improvement with SLNs in cognitive ability through the reduction in escape latency time during behavioural studies, together with significant improvement in various biochemical parameters and body weight gain was observed in AD-induced rats. Histopathological images of different rat organs showed no perceptible change(s) in tissue morphology. Overall, these preclinical findings successfully demonstrate improved anti-AD efficacy, superior nasal mucoadhesion and permeation, extended drug release, improved patient compliance potential, safety and robustness of the developed lipidic nanoconstructs of FA through intranasal route.

Developing a Validated HPLC Method for Quantification of Ceftazidime Employing Analytical Quality by Design and Monte Carlo Simulations.

BACKGROUND: Ceftazidime, a third-generation cephalosporin, is widely used in the treatment of lung infections, often given as "off-label" nebulization. There is a need to develop a sensitive and robust analytical method to compute aerodynamic properties of ceftazidime following nebulization. OBJECTIVE: The current study entails development of a simple, accurate, and sensitive HPLC method for ceftazidime estimation, employing the principles of analytical quality-by-design (AQbD) and Monte Carlo simulations. METHOD: Selection of critical material attributes (CMAs) affecting method performance was accomplished by factor screening exercises. Subsequently, the influential CMAs, i.e., mobile phase ratio and flow rate, were systemically optimized using a face-centered cubic design for the chosen critical analytical attributes (CAAs). The factor relationship(s) between CMAs and CAAs was explored employing a 3 D-response surface and 2 D-contour plots, followed by numerical as well as graphical optimization, for establishing the optimal chromatographic conditions. The obtained method operable design region was validated by Monte Carlo simulations for defect rate analysis. RESULTS: The optimized HPLC conditions for estimating ceftazidime were acetonitrile to acetic acid solution (75:25) as mobile phase at a flow rate of 0.7 mL/min, leading to Rt of 4.5 min and peak tailing ≤2. Validation studies, as per International Conference on Harmonization Q2(R1) guidance, demonstrated high sensitivity, accuracy, and efficiency of the developed analytical method with an LOD of 0.075 and LOQ of 0.227 µg/mL. Application of this chromatographic method was extrapolated for determining aerodynamic performance by nebulizing ceftazidime at a flow rate of 15 L/min using a next-generation impactor. The study indicated superior performance, sensitivity, and specificity of the developed analytical system for quantifying ceftazidime. CONCLUSIONS: Application of an AQbD approach, coupled with Monte Carlo simulations, aided in developing a robust HPLC method for estimationof ceftazidime per se and on various stages of impactor. HIGHLIGHTS: (i) QbD-enabled development of robust RP-HPLC method for ceftazidime quantification, (ii) Analytical method optimization employing Risk Assessment and Design of Experiments, (iii) Design space verification and defect rate analysis using Monte Carlo simulations, (iv) Chromatographic method validation as per ICH Q2 R1 guidelines and (v) Quantitative estimation of ceftazidime on various stages of impactor.

QbD-steered development of mixed nanomicelles of galantamine: Demonstration of enhanced brain uptake, prolonged systemic retention and improved biopharmaceutical attributes.

PURPOSE: Numerous oral treatment options have been reported for neurological disorders, especially Alzheimer's disease (AD). Galantamine (GAL) is one of such drugs duly approved for management of AD. However, it exhibits poor brain penetration, low intestinal permeation and requires frequent dosing in AD treatment. The present studies, accordingly, were undertaken to develop DSPE-PEG 2000-based micelles loaded with GAL for efficient brain uptake, improved and extended pharmacokinetics, along with reduced dosing regimen. METHODS: Mixed nanomicelles (MNMs) were systematically formulated using QbD approach, and characterized for morphology, entrapment efficiency andin vitrodrug release. RESULTS: Studies on CaCo-2 and neuronal U-87 cell lines exhibited substantial enhancement in the cellular permeability and uptake of the developed MNMs. Pharmacokinetic studies performed on rats showed significantly improved values of plasma AUC (i.e., 2.28-fold, p < 0.001), ostensibly due to bypassing of hepatic first-pass metabolism and improved intestinal permeability, together with significant rise in MRT (2.08-fold, p < 0.001) and tmax (4.80-fold; p < 0.001) values, indicating immense potential for prolonged drug residence in body.Besides, substantial elevation in brain drug levels, distinctly improved levels of biochemical parameters in brain homogenates and cognitive improvement in ß-amyloid-treated rats, testify the superiority in MNMs in therapeutic management of AD. CONCLUSIONS: The preclinical findings of the developed nanocarrier systems successfully demonstrate the notable potential of enhanced drug efficacy, extended duration of action and improved patient compliance.

Systematic Development of Drug Nanocargos Using Formulation by Design (FbD): An Updated Overview.

Nanostructured drug delivery formulations have lately gained enormous attention, contributing to their systematic development. Issuance of quality by design (QbD) guidelines by ICH, FDA, and other federal agencies, in this regard, has notably influenced the overall development of drug products, enabling holistic product and process understanding. Owing to the applicability of QbD paradigms, a science lately christened as formulation by design (FbD) has been dedicated exclusively to QbD-enabled drug product development. Consisting of the principal elements of design of experiments (DoE), quality risk management (QRM), and QbD-enabled product comprehension as the fundamental tools in the implementation of FbD, a variety of drug nanocargos have been successfully developed with FbD paradigms and reported in the literature. FbD aims to produce novel and advanced systems utilizing nominal resources of development time, work effort, and money. A systematic FbD approach envisions the entire developmental path through pivotal milestones of risk assessment, factor screening and optimization (both using appropriate experimental designs), multivariate statistical and optimum search tools, along with response surface modeling, usually employing suitable computer software. The design space is one of the fundamental elements of FbD providing the most sought-after regulatory flexibility to pharma companies, postapproval. The present paper provides a bird's eye view of the fundamental aspects of FbD terminology, methodology, and applications in the development of a wide range of nanocargos, as well as a discussion of trends from both technological and regulatory perspectives.

Supersaturated LFCS type III self-emulsifying delivery systems of sorafenib tosylate with improved biopharmaceutical performance: QbD-enabled development and evaluation.

The current studies investigate the application of quality by design-enabled type III self-emulsifying delivery system (Type III-SEDDS) of sorafenib tosylate (SFN) in improving its biopharmaceutical attributes. Initially, lipidic and emulsifying excipients were selected by carrying out solubility and phase titration experiments. After screening studies using Taguchi OA design, Type III-SEDDS were further optimised using D-optimal mixture design. The prepared formulations were assessed for globule size, zeta potential and percent of drug release. Following graphical optimisation, the optimum formulation was earmarked and further supersaturated to form saturated Type III-SEDDS (Sat-Type III-SEDDS) using a combination of HPMC and PVP to improve the stability of the formulation for a prolonged period. In vitro drug release of Type III-SEDDS study indicated approximately 8-fold improvement in dissolution rate over the pure powder drug. Cell uptake studies demonstrated higher uptake of dye-loaded Type III-SEDDS formulations in Caco-2 cells vis-à-vis plain dye. Cytotoxicity assay on Hep G2 cells revealed significant reduction in cell growth with Type III- and Sat-Type III-SEDDS vis-à-vis the pure drug. Furthermore, in situ permeation studies carried out using Wistar rats exhibited nearly 8.3- to 10.2-fold augmentation in permeation and absorption parameters of the drug from the Type III- and Sat-Type III-SEDDS, respectively, vis-à-vis the pure drug. Pharmacokinetic studies indicated nearly 3.98- and 3.62-fold improvement in AUC0-72, and 8.01- and 5.42-fold in Cmax, along with 0.25-fold decrease in Tmax of the drug from Type III- and Sat-Type III-SEDDS, respectively, in comparison with the SFN suspension. Furthermore, high degree of level A linear correlation was established between fractions of drug dissolved (in vitro) and of drug absorbed (in vivo) at the corresponding time points for Sat-Type III-SEDDS and pure drug, whereas the Type III-SEDDS exhibited a nonlinear relationship. Stability studies indicated the robustness of Sat-Type III-SEDDS, when stored at 25 °C for 3 months. Overall, the manuscript documents the successful systematic development of SFN-loaded Sat-Type III-SEDDS with distinctly improved biopharmaceutical performance. Graphical abstract.

QbD-steered development and validation of an RP-HPLC method for quantification of ferulic acid: Rational application of chemometric tools.

The present work describes the systematic development of a simple, rapid, sensitive, robust, effective and cost-effective reversed-phase high performance liquid chromatographic method for quantitative analysis of ferulic acid using analytical quality by design paradigms. Initially, apt wavelength for the analysis of ferulic acid was selected employing principal component analysis as the chemometric tool. An Ishikawa fishbone diagram was constructed to delineate various plausible variables influencing analytical target profile, viz. peak area, theoretical plate count, retention time and peak tailing as the critical analytical attributes. Risk assessment using risk estimation matrix and factor screening studies employing Taguchi design aided in demarcating two critical method parameters, viz. mobile phase ratio and flow rate affecting critical analytical attributes. Subsequently, the optimum operational conditions of the liquid chromatographic method were delineated using face-centred composite design. Multicollinearity among the chosen factors for optimization was analyzed by the magnitude of variance inflation factor optimized analytical design space, providing optimum method performance, was earmarked using numerical and graphical optimization and corroborated using Monte Carlo simulations. Validation, as per the ICH Q2(R1) guidelines, ratified the efficiency and sensitivity of the developed novel analytical method of ferulic acid in the mobile phase and the human plasma matrix. The optimal method used a mobile phase, comprising of acetonitrile: water (47:53% v/v, pH adjusted to 3.0 with glacial acetic acid), at a flow rate of 0.8 mL·min-1, at a λmax of 322 nm using a C18 column. Use of principal component analysis unearthed the suitable wavelength for analysis, while analytical quality by design approach, along with Monte Carlo simulations, facilitated the identification of influential variables in obtaining the "best plausible" validated chromatographic solution for efficient quantification of ferulic acid.

Stimuli-Responsive Systems with Diverse Drug Delivery and Biomedical Applications: Recent Updates and Mechanistic Pathways.

With the advent of "intelligent" polymeric systems, the use of stimuli-responsive in situ gelling systems has been revolutionized. These interesting polymers exist as free-flowing aqueous solutions before administration and undergo a phase transition to form a viscoelastic gel in a physiological environ through various stimuli such as temperature, pH, solvent, biochemical, magnetic, electric, ultrasound, and photo-polymerization. These smart polymers are endowed with numerous merits such as ease of administration, sustained release, reduced frequent administration with improved patient compliance, and targeted and spatial delivery of a drug with reduced frequency of side effects. Concerted efforts are being made to modify these polymers synthetically because they hold immense potential in various fields such as polymer chemistry, materials science, pharmaceutics, bioengineering medicine, and chemical engineering. In addition to novel drug delivery, these smart polymeric systems have exhibited tremendous applications in tissue engineering, regenerative biomedicine, molecular imprinting, cancer therapy, gene delivery, theranostic and other applications. The current review mainly focuses on the fundamental principles involved during in situ gelling, use of various "smart" drug-delivery formulation systems through diverse routes for their administration, as well as their well-documented biomedical applications. The pertinent literature, marketed formulations, and recent advances on these stimuli-responsive sol-gel-transforming systems are also discussed.

Nanoporous metal organic frameworks as hybrid polymer-metal composites for drug delivery and biomedical applications.

Metal organic frameworks (MOFs), porous hybrid polymer-metal composites at the nanoscale, are recent innovations in the field of chemistry; they are novel polymeric materials with diverse biomedical applications. MOFs are nanoporous materials, consisting of metal ions linked together by organic bridging ligands. The unique physical and chemical characteristics of MOFs have attracted wider attention from the scientific community, exploring their utility in the field of material science, biology, nanotechnology and drug delivery. The practical feasibility of MOFs is possible owing to their abilities for biodegradability, excellent porosity, high loading capacity, ease of surface modification, among others. In this regard, this review provides an account of various types of MOFs, their physiochemical characteristics and use in diverse disciplines of biomedical sciences - with special emphasis on drug delivery and theranostics. Moreover, this review also highlights the stability and toxicity issues of MOFs, along with their market potential for biomedical applications.

Phytoconstituents as pharmacotherapeutics in rheumatoid arthritis: challenges and scope of nano/submicromedicine in its effective delivery.

OBJECTIVES: The present review explores the therapeutic application of herbals in rheumatoid arthritis (RA) therapy, and how nano/submicromedicine can be fit in the scope of its therapeutic delivery in RA has been addressed. KEY FINDINGS: Incorporation of bioactive such as polyphenols, thymoquinone, resveratrol, hesperidin, curcumin, celastrol and gambogic acid in a dose-dependent manner showed quite high efficacy for the treatment of RA. It can be attributed to their targeting ability against various inflammatory mediators including nitric oxide (NO), cytokines, chemokines, adhesion molecules, NF-kß, lipoxygenase (LOXs) and arachidonic acid (AA). Despite the presence of significant merits, the use of these bioactives has several demerits such as poor bioavailability as a function of low aqueous solubility and higher first-pass metabolism upon oral administration. The impact of nano/submicromedicine in the delivery of these bioactives against RA has gained wider attention owing to bioavailability enhancement, higher stability and better efficacy. CONCLUSION: Phytoconstituents possess immense potential in RA pharmacotherapy, but the obstacles for their effective delivery can be overcome using nano/submicrocarrier-based drug delivery technologies, which maximize the efficacy of these herbal antirheumatic drugs without any systemic adverse effects.

Nanoemulsion for the Effective Treatment and Management of Anti-tubercular Drug Therapy.

BACKGROUND: Tuberculosis is considered as one of the deadliest diseases of human existence. Since ancient age the treatment of tuberculosis has been highly challenging primarily owing to the pathogenic nature of the Mycobacterium and its diverse spots of localization in human body including lungs, liver, spleen, eye, meninges and lymph nodes. METHODS: The conventional drug therapy employed for the treatment of tuberculosis is not highly satisfactorily owing to low oral bioavailability of the drugs. The evolution of nano-technology recently in few decades has completely revolutionized the treatment of diverse diseases and so is the tuberculosis. Nanotechnology not only possesses enormous potential for improving the biopharmaceutical performance, but also allows the delivery of therapeutic molecules to the desired site of action. Diverse types of nanocarriers have been employed for the treatment of tuberculosis infections. In this regard, nanoemulsions are considered as one of the promising alternatives for augmenting the bioavailability of the antitubercular drugs through oral route for improving their therapeutic efficacy. CONCLUSION: The nanoemulsion loaded with antitubercular drugs can easily cross the biological barriers to reach the systemic circulation and consequently in the target for reducing the load of Mycobacterium tuberculosis. Besides, the lipidic nature of such systems facilitates targeting of the drugs to the lymph nodes, thus improves drug bioavailability and reduction of the dosing frequency. In lieu of this, the present article compiles the basics of nanoemulsions in brief along with an updated account on their applications in delivering antitubercular drugs for enhanced immunization. Moreover, overview of patent literature published in this area has also been included in the manuscript.

Anti-Alzheimer's potential of berberine using surface decorated multi-walled carbon nanotubes: A preclinical evidence.

Carbon nanotubes (CNTs), a sub-family of fullerenes, are nanosized seamless cylinders of graphene sheets with enormous drug loading potential. The current studies entail the systematic development of berberine (BRB)-loaded multiwalled carbon nanotubes (MWCNTs) with polysorbate and phospholipid coating for effective management of Alzheimer's Disease (AD). For systematic optimization using design of experiment (DoE), a central composite design (FCCD) was employed and the optimized formulation was choosen using numerical desirability function. Optimized formulation exhibited particle size of 186nm, 68.6% drug adsorption and amount of drug released in 16h (Q16h) of 96%. Degree of carboxylation was observed to be 36%. FTIR and FESEM studies confirmed the coating of polysorbate and phospholipid onto the MWCNTs side walls. Confocal studies ratified the uptake potential of BRB-loaded MWCNT formulations on SH-SY5Y cell lines. In vivo pharmacokinetic studies in rats showed significant improvement in the rate and extent of drug absorption in the plasma and brain tissues, both, vis-a-vis pure drug. Behavioral assessment employing Morris Maze test demonstrated the enhanced performance efficiency of the formed MWCNT complexes. Moreover, the phospholipid-coated and the polysorbate-coated MWCNTs exhibited remarkable recovery in memory performance from 18th to 20th day vis-a-vis other groups. Maintenance of normal biochemical levels in brain tissue demonstrated the potential of these coated MWCNTs in reducing ß-amyloid induced AD. The studies, in a nutshell, demonstrate significant potential of polysorbate/phospholipid coated MWCNTs of BRB in holistic management of AD.

Lipid-based Vesicular Nanocargoes as Nanotherapeutic Targets for the Effective Management of Rheumatoid Arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is an immune mediated joint-based chronic inflammatory disorder recognized by joint inflammation, destruction, pain and remission. Currently, numerous pharmacotherapeutic strategies have gained immense popularity in RA therapy and improving the patient life. METHODS: Besides, it exhibits numerous drawbacks such as requirement of high dose of drugs, unavoidable adverse effects and diseases remission. Thus, use of currently available pharmacotherapeutics employing conventional formulations can only provide therapeutic effects to a certain extent. RESULTS: Recent advancements in nanotechnology-based lipidic vesicular nanocarriers have led provided improved efficacy and safety for the anti-rheumatic drugs. These include liposomes, stealth liposomes, ethosomes, transfersomes, etc., which have shown their potential to improve the therapeutic efficacy of antirheumatic drugs with lesser toxicity. Although the results of animal models for use of lipid vesicular nanocarriers for drug targeting in RA have been found to be highly promising, but lack of sufficient data in a clinical setup are still evident to demonstrate their practical utility in patient populations. In this regard, considerable research studies are required for evaluating the efficacy and safety of the aforementioned nanocarriers in RA through clinical studies. CONCLUSION: The present review, therefore, covers the brief pathophysiology of RA, current medication and their challenges in RA therapy. Besides, an extensive account on recent advancements in novel lipid vesicular nanocarriers in RA therapy has also been addressed with special emphasis on the patent literature too.