Metal-organic frameworks: Drug delivery applications and future prospects.

Background and purpose: Metal-organic frameworks (MOFs) have gained incredible consideration in the biomedical field due to their flexible structural configuration, tunable pore size and tailorable surface modification. These inherent characteristics of MOFs portray numerous merits as potential drug carriers, depicting improved drug loading, site-specific drug delivery, biocompatibility, biodegradability, etc. Review approach: The current review article sheds light on the synthesis and use of MOFs in drug delivery applications. In the beginning, a brief overview of the key components and efficient fabrication techniques for MOF synthesis, along with its characterization methods, have been presented. The MOFs-based formulations have been critically discussed. The application of the design of experiments (DoE) approach to optimize MOFs has been elucidated. The MOFs-based formulations, especially the application of stimuli-responsive MOFs for site-specific drug delivery, have been deciphered. Along with drug release kinetic models, several administration methods for MOFs have also been enunciated. Subsequently, MOFs as future potential drug carriers have been elaborated. Key results and conclusion: Recently, MOFs have emerged as versatile drug delivery carriers possessing customization potential and meeting the needs of spatio-temporal drug delivery. Researchers have devised several environment-friendly approaches for MOF construction and surface modification. Owing to stimuli-responsive potential, MOFs have demonstrated their prominent therapeutic efficacy via several routes of administration. The numerous benefits of MOFs would certainly open up a new vista for its novel drug delivery applications.

Design of cobalt-doped graphene quantum dot-decorated vanadium pentoxide nanosheet-based Off-On fluorescent sensor system for tiopronin sensing.

Despite the high medicinal value of tiopronin, there are substantial adverse effects such as yellow skin, yellow eyes, muscle aches, etc. Therefore, there is a huge necessity to identify tiopronin using advanced sensors in provided samples. Recently, the preference for graphene quantum dots (GQDs) and inorganic nanomaterial-based fluorescent sensors for the detection of pharmaceuticals has been extensively documented due to their plentiful advantages. Therefore, in this work, the cobalt-doped GQDs decorated vanadium pentoxide nanosheet-based fluorescence switch 'Off-On' sensor (Co-GQDs@V2O5-NS) was designed for highly sensitive and selective detection of tiopronin. Briefly, the green synthesis of highly fluorescent Co-GQDs was carried out using a hydrothermal method. Meanwhile, the synthesis of V2O5-NS was synthesized using the liquid exfoliation method. The synthesis of Co-GQDs@V2O5-NS was accomplished wherein Co-GQDs adsorbed on the surface of V2O5-NS that offered the quenching of fluorescence of Co-GQDs. Afterward, the addition of tiopronin into the quenched probe disclosed the proportional recovery of fluorescence of Co-GQDs. Here, the addition of tiopronin provides the decomposition of V2O5-NS and conversion into the V4+ that aids in releasing the quenched fluorescence of Co-GQDs. The limit of detection and linearity range for tiopronin was found to be 1.43 ng/mL and 10-700 ng/mL, respectively. Moreover, it demonstrated high selectivity, good stability at experimental conditions, and practicality in analyzing tiopronin in spiked sample analysis. Hence, the designed Co-GQDs@V2O5-NS nanosized sensor enables high sensitivity, selectivity, simplicity, label-free, and eco-friendly tiopronin recognition. In the future, the utility of Co-GQDs@V2O5-NS can open a new door for sensing tiopronin in provided samples.

Stimuli-Responsive Design of Metal-Organic Frameworks for Cancer Theranostics: Current Challenges and Future Perspective.

Scientific fraternity revealed the potential of stimuli-responsive nanotherapeutics for cancer treatment that aids in tackling the major restrictions of traditionally reported drug delivery systems. Among stimuli-responsive inorganic nanomaterials, metal-organic frameworks (MOFs) have transpired as unique porous materials displaying resilient structures and diverse applications in cancer theranostics. Mainly, it demonstrates tailorable porosity, versatile chemical configuration, tunable size and shape, and feasible surface functionalization, etc. The present review provides insights into the design of stimuli-responsive multifunctional MOFs for targeted drug delivery and bioimaging for effective cancer therapy. Initially, the concept of cancer, traditional cancer treatment, background of MOFs, and approaches for MOFs synthesis have been discussed. After this, applications of stimuli-responsive multifunctional MOFs-assisted nanostructures that include pH, light, ions, temperature, magnetic, redox, ATP, and others for targeted drug delivery and bioimaging in cancer have been thoroughly discussed. As an outcome, the designed multifunctional MOFs showed an alteration in properties due to the exogenous and endogenous stimuli that are beneficial for drug release and bioimaging. The several reported types of stimuli-responsive surface-modified MOFs revealed good biocompatibility to normal cells, promising drug loading capability, target-specific delivery of anticancer drugs into cancerous cells, etc. Despite substantial progress in this field, certain crucial issues need to be addressed to reap the clinical benefits of multifunctional MOFs. Specifically, the toxicological compatibility and biodegradability of the building blocks of MOFs demand a thorough evaluation. Moreover, the investigation of sustainable and greener synthesis methods is of the utmost importance. Also, the low flexibility, off-target accumulation, and compromised pharmacokinetic profile of stimuli-responsive MOFs have attracted keen attention. In conclusion, the surface-modified nanosized design of inorganic diverse stimuli-sensitive MOFs demonstrated great potential for targeted drug delivery and bioimaging in different kinds of cancers. In the future, the preference for stimuli-triggered MOFs will open a new frontier for cancer theranostic applications.

Isolation and identification of hair growth potential fraction from active plant extract of Blumea eriantha DC grown in Western Ghat of India: In silico study.

BACKGROUND: In Aayurveda, Blumea eriantha DC has been used in the management of various diseases and is found to exhibit antioxidant and anti-hyperlipidemic, hypoglycemic, anti-diarrhoeal, larvicidal, antimicrobial properties. OBJECTIVE: The present study has focused on isolation of the active fraction from B. eriantha DC extract and to investigate its effect as a hair growth promoter along with identification of phytoconstituent(s) responsible for hair growth activity and its probable mechanism of action. MATERIALS AND METHODS: Our work introduces an effective isolation protocol for the active fraction from B. eriantha DC extract using chromatographic techniques. Fraction A was isolated by using mobile phase toluene:acetone (9:1). In-vitro and in-vivo methods were executed for the evaluation of hair growth activity. Moreover, the docked conformations of the isolated phytoconstituent Dimethyl sulfone was compared to Minoxidil for selected proteins namely 2FGF, 2PVC and 4U7P. The PDB identifications 2PVC (DNMT3L recognizes unmethylated histone H3 lysine 4), 4U7P (Crystal structure of DNMT3A-DNMT3L complex and 2FGF (Human Basic Fibroblast Growth Factor) were downloaded from Protein Data Bank. RESULTS: The study data revealed that B. eriantha DC alcoholic extracts exhibited prominent hair growth activity and it was affirmed that Dimethyl sulfone a phyto-constituent isolated from B. eriantha DC alcoholic extract contributed for the same. CONCLUSION: The findings strongly suggest hair growth promotion potential of the extract of B. eriantha DC.

Colon targeted dosage form of Capecitabine using folic acid anchored modified carbon nanotube: in vitro cytotoxicity, apoptosis and in vivo roentgenographic study.

OBJECTIVE: Development of dosage form comprising of Capecitabine loaded carbon nanotubes for its targeted delivery to the colon. METHOD: Single walled carbon nanotubes (SWCNT) were functionalized by -COOH and Chitosan along with Folic acid. Capecitabine was loaded in these SWCNT's, and the system was analyzed by FTIR, SEM and Raman spectroscopy. Percent drug loading was assessed and the cytotoxicity (COLO320DM and HT29) was verified by using MTT and SRB assay. The apoptosis study was carried out by flowcytometry. The system was enclosed in an enteric coated capsule with pH sensitive polymers and characterized for invitro disintegration, dissolution and invivo roentgenographic studies. RESULTS: FTIR, Raman and XRD studies indicated the confirmation of attachments, whereas SEM exhibited size range of 200-500 nm. Drug loading capacity was observed to be 94.63 ± 1.07%. Cytotoxicity studies of Capecitabine and FA-CHI-F-SWCNT-Capecitabine against COLO320DM by using MTT assay showed that FA-CHI-F-SWCNT- Capecitabine exhibited 86.45 ± 0.5788% inhibition whereas pure Capecitabine showed 50.52 ± 0.3106% inhibition. Against HT29, the % inhibition was observed to be 82.76 ± 0.4668% and 56.41 ± 0.2316% respectively for FA-CHI-F-SWCNT-Capecitabine and pure Capecitabine. In case of SRB assay of COLO320DM, the FA-CHI-F-SWCNT-Capecitabine exhibited 89.62 ± 0.4095% inhibition and Capecitabine showed 84.36 ± 0.2559% inhibition, whereas against HT29, FA-CHI-F-SWCNT-Capecitabine showed 81.36 ± 0.2958% inhibition and Capecitabine exhibited 90.62 ± 0.4196% inhibition. CONCLUSION: FA-CHI-F-SWCNT loaded system revealed better cytotoxicity as compared with pure Capecitabine against two different cell lines. Invivo studies revealed that the prepared capsule formulation remained intact in the stomach thereby preventing drug release in the gastric milieu.

Green synthesis of silver, iron and gold nanoparticles of lycopene extracted from tomato: their characterization and cytotoxicity against COLO320DM, HT29 and Hella cell.

Our study aimed at development of Silver, Iron and Gold nanoparticles of Lycopene isolated from tomato by using green synthesis technique and to evaluate its anticancer potential against colorectal and cervical cancer. Lycopene was extracted by benzene extraction method and the silver, iron and gold nanoparticles were developed by green synthesis method. 1% aqueous extract of isolated Lycopene was mixed with 1% solutions of AgNO3, FeCl3 and HAuCl4 solutions and incubated at ambient temperature for 3-4 h separately and observed for the color change which is an indicative of formation of the nanoparticles. The prepared nanoparticles were characterized by FTIR, SEM, XRD analysis and evaluated for their antimicrobial potential. The cytotoxicity studies were carried out by in vitro assay like MTT, SRB and Tryphan blue method against Colo 320 DM, HT 29, and Hella. SEM showed nanosized particles of 50-100 nm range, whereas no antimicrobial activity was exhibited by the prepared nanoparticles. In MTT assay the LyAgNP showed maximum 41.41 ± 0.4124% inhibition against COLO320DM, whereas LyGNP exhibited 41.47 ± 0.4469% inhibition against HT 29 and LyAgNP showed 40.9 ± 0.6908% inhibition against Hella cells. In SRB assay LyAgNP showed maximum 82.68 ± 1.1798% inhibition against COLO320DM, whereas LyGNP exhibited maximum 91.21 ± 0.2372% inhibition against HT29 and 87.98 ± 0.5878% inhibition against Hella cells. In tryphan blue assay against COLO320DM, HT29 and Hella cells, the maximum inhibition exhibited by the prepared nanoparticles were observed as LyGNP 83.45 ± 0.4694%, LyAgNP 88.05 ± 0.1870% and LyAgNP65.47 ± 0.4766%. We conclude that the developed nanoparticles of Lycopene exhibited potential anticancer activity against Colorectal and cervical cancer cell as compared with pure Lycopene.

Silk industry waste protein: isolation, purification and fabrication of electrospun silk protein nanofibers as a possible nanocarrier for floating drug delivery.

Amongst assorted regio-selective and targeted oral drug delivery strategies accepted for the gastro-retentive drug delivery system (GRDDS), the floating drug delivery system (FDDS) holds a major share as clinically accepted formulations. The major objective of the present investigation was to explore the silk industry waste protein, silk fibroin (SF) as a possible electrospun nanocarrier for the FDDS. In a nutshell, electrospinning (ES) is one of the flexible and astonishing strategies for the fabrication of porous electrospun nanofibers (NFs), which offers the potential to amend the floating profile, dissolution rate, solubility, and release patterns of the drug, etc as per compendial requirements. Looking at the prospects of floating SF-NFs preparation, we have isolated and lyophilized the SF from industrial waste cocoons and prepared drug-loaded SF single polymer nanofibers (SPN). Lafutidine (LF) being a good candidate for GRDDS selected as a model drug, which is an excellent proton pump inhibitor, mainly used in the treatment of gastric ulcers. Finally, the obtained LF loaded SF-NFs (LF-SF-NFs) were successfully analyzed for physicochemical characteristics, porosity, swelling index, antioxidant activity, mucoadhesion strength, floating properties, enzymatic degradation, and accelerated stability study, etc. Further, these LF-SF-NFs were evaluated for percent drug content, weight variation, in-vitro dissolution in 0.1 N hydrochloric acid (HCl, pH:1.2) and fasted state simulated gastric fluid (FSSGF), and accelerated stability study. It has shown significant floating time >18 h, about 99% ± 0.58% floating buoyancy with sustained release up to 24 h. LF-SF-NFs showed good compatibility, entrapment efficiency, antioxidant activity, mucoadhesion strength, enzymatic degradation, and long term stability. Soon, the essential floating and drug release profiles can claim single polymer (SF) based electrospun protein NFs as a possible novel oral nanocarrier for FDDS.

Discovery of potential inhibitors for phosphodiesterase 5A, sodium-potassium pump and beta-adrenergic receptor from Terminalia arjuna: in silico approach.

The aim of this work was to perform in silico analysis of selected biomolecules from Terminalia arjuna (T. arjuna) by using virtual screening, molecular docking and pharmacophore modeling. Reported 30 biomolecules of T. arjuna were used as ligands. Grip-based docking was carried out to produce the target-specific complex model using vLife MDS 4.4 software. Docked conformations of the selected T. arjuna biomolecules resulted in eight potential biomolecules namely Casuarinin, Luteolin, Pelargonidin, Arjunin, Castalagin, Punicalagin, Kaempferol and Quercetin with major interactions and exhibited good affinity to the residues of protein targets. Developed pharmacophore models have suggested minimum pharmacophoric features required in the biomolecule so as to show standard like activity. Interestingly, Casuarinin showed multiple inhibitions on phosphodiesterase 5A and sodium-potassium pump whereas Pelargonidin on phosphodiesterase 5A and beta-adrenergic protein targets. Conclusively, this study provides a suitable platform for discovery of novel inhibitors from natural source for heart disorders.

Green synthesis of silver and iron nanoparticles of isolated proanthocyanidin: its characterization, antioxidant, antimicrobial, and cytotoxic activities against COLO320DM and HT29.

BACKGROUND: In the current research, we have developed silver and iron nanoparticles of isolated proanthocynidin (PAC) from grape seed by green synthesis and evaluated for antimicrobial, antioxidant activity and in vitro cytotoxicity against colon cancer cell lines. RESULTS: One percent solution of isolated proanthocynidin in water was vigorously mixed with 1% silver nitrate and 1% ferric chloride solution and kept for 4 h, to yield PACAgNP and PACFeNP. The synthesized nanoparticles were characterized by UV, FTIR, XRD, and SEM analysis and evaluated for antimicrobial potential against selected microbes. Moreover, the synthesized nanoparticles were studied for DPPH assay and in vitro cytotoxicity using colon cancer cell lines COLO320DM and HT29 (MTT, SRB, and Trypan blue assay). UV spectroscopy confirmed the development of nanoparticles. SEM analysis showed that the particles were aggregated in the size range of 50 to 100 nm. Antimicrobial potential was found to be less against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, whereas cytotoxicity of PACAgNP and PACFeNP against COLO320DM and HT29 exhibited promising results as compared to the pure PAC. PACAgNP and PACFeNP exhibited 20.83 ± 0.33% and 18.06 ± 0.60% inhibition, respectively, against DPPH radical, whereas pure PAC showed 16.79 ± 0.32% inhibition and standard (ascorbic acid) exhibited 98.73 ± 0.18% inhibition of DPPH radical. CONCLUSION: The silver and iron nanoparticles were successfully developed by green synthesis method using isolated proanthocynidin which is economical and eco-friendly. The use of metal nanoparticles may open up a new opportunity for anticancer therapies to minimize the toxic effects of available anticancer drugs specifically in targeting specific site.

A remarkable in vitro cytotoxic, cell cycle arresting and proapoptotic characteristics of low-dose mixed micellar simvastatin combined with alendronate sodium.

The objective of the present study was to screen the effect of increased simvastatin (SVS) solubility, through mixed micelles as a model approach, on in vitro anticancer efficacy in combination with hydrophilic alendronate sodium (ADS) as a strategy to improve therapeutic efficacy and to repositioning the existing drugs. The SVS-loaded mixed micelles (SVS-MMs) composed of TPGS and Poloxamer-407 were prepared using the film dispersion method and characterized for SVS loading and mean particle size. The optimized SVS-MMs were physically mixed with plain ADS (SVS + ADS MMs) and screened for in vitro cytotoxicity using MTT assay and cell cycle arresting and apoptotic activities using FACS technique. The optimized SVS-MMs showed maximum SVS loading (97.3 ± 2.3%) with minimum particle size (206 ± 8 nm). The SVS + ADS MM treatment significantly (P < 0.001) inhibited the cell growth with low IC50 values against all cells (A549: 0.037 ± 0.028 µg/mL, MDAMB-231: 0.172 ± 0.031 µg/mL, PC-3: 0.022 ± 0.015 µg/mL). Further, the SVS + ADS MM treatment significantly inhibited the cell multiplication in the S phase and resulted in high % of late apoptotic and necrotic cells at low concentration (0.05 and 0.15 µg/mL) as compared other test samples. The above results revealed the significance of encapsulating SVS in the core of MMs (improved solubility), and high efficacy and quick effect of SVS + ADS MM treatment against all cell lines screened. Graphical abstract.

Pharmaceutical applications of electrospinning.

Development of tailor-made pharmaceutical nanofibers has gained vital prominence due to ease of fabrication and versatility of electrospinning (ES). ES is one of the flexible and, wonderful strategies for the fabrication of nanofibers. ES unit comprises a supplier of high voltage current, a syringe (pump), spinneret and a metal plate collector. The obtained nanofibers are optimized by manipulating process and formulation variables Viz: polymer/drug resolution (viscosity, concentration, physical phenomenon, molecular mass) and the environmental conditions (humidity, temperature). The electrospun nanofibers can be used for loading of the drug, amorphization of a crystalline API and an increase in its physical storage stability. ES technique enables mixing of two or more API and may facilitate or inhibit the burst release of a drug, along with attainment of modified release. Additionally, nanofibers demonstrate a reduction in overall dose needed for the therapeutic activity, by improving dissolution and bioavailability of the drugs. The current review is an attempt to focus on ES method, the optimization parameters, and pharmaceutical applications of the electrospun nanofibers.

Sericin Inhibits Devitrification of Amorphous Drugs.

The purpose of the present investigation was to analyze devitrification of amorphous drugs such as lornoxicam, meloxicam, and felodipine in the presence of sericin. The binary solid dispersions comprising varying mass ratios of drug and sericin were subject to amorphization by spray drying, solvent evaporation, ball milling, and physical mixing. Further, obtained solid dispersions (SDs) were characterized by HPLC, ATR-FTIR, H1NMR, molecular docking, accelerated stability study at 40°C and 75 ± 2% RH (XRD and DSC), and in vitro dissolution studies. The HPLC analysis indicated no decomposition of the drugs during the spray drying process. From ATR-FTIR, NMR, and molecular docking study, it was revealed that H-bonding played a vital role in amorphous drug stabilization. An excellent devitrification inhibition was observed in case of lornoxicam (SDLS3) and meloxicam (SDMS3) SDs prepared by spray drying. On the other hand, spray-dried SD of felodipine (SDFS3) showed traces of microcrystals. The percent crystallinity of SDLS3, SDMS3, and SDFS3 was found to be 7.4%, 8.23%, and 18.31% respectively indicating adequate amorphization. The dissolution performance of SDLS, SDMS, and SDFS after 3 months showed > 85% than SDs prepared by other methods. Thus, sericin significantly inhibited crystallization and was responsible for amorphous state stabilization of pharmaceuticals.

Development of stable emulsified formulations of Terminalia arjuna for topical application: evaluation of antioxidant activity of final product and molecular docking study.

Objective: The aim of this work was to develop stable emulsified formulations containing Terminalia arjuna (T. arjuna) extract and to assess antioxidant potential of the final product with in silico molecular screening. Methods: Terminalia arjuna emulsified formulations were prepared by application of ternary phase diagram design and were evaluated for phytochemical screening, solubility studies, ex vivo permeation study, DPPH free radical scavenging assay, anti-tyrosinase activity, skin irritation, stability studies, molecular docking study, and pharmacophore modeling. Results: Phytochemical screening resulted in the presence of secondary metabolites. The result of the solubility study exhibited that olive oil, tween 80, and PEG 400 could be the most appropriate combination for preparation of the emulsified system. The ex vivo study showed adequate release from its emulsified formulation. Globule size determination and Zeta potential analysis indicate the stability of the emulsified system. The result of DPPH free radical scavenging activity and anti-tyrosinase activity of the final product were satisfactory. Skin irritation test on albino rats resulted in no allergic dermal effects. All the prepared formulations were found to be stable upon storage for 3 months. Molecular docking resulted in antioxidant potential via tyrosinase inhibitory mechanism mainly by hydrogen bonding interaction with His60B, Glu158B, His208B, Asn205B, Met215B, His42B, and Asn57B whereas ionic interactions by Arg209B and Val218B of tyrosinase. Pharmacophore modeling describes the similarity features with the standard. Conclusions: The results suggest that developed emulsified formulations with T. arjuna extract for topical application demonstrate interesting attributes to be explored as potential pharmaceutical products.

Development of High-Strength Extended-Release Multiparticulate System by Crystallo-co-agglomeration Technique with Integration of Central Composite Design.

The number of unit operations to be followed in the preparation of tablets was cumbersome and may introduce material as well as process-related critical parameters which may negatively affect the quality of final formulation. The hypothesis of the present research was to develop directly compressible, high-strength extended-release spherical agglomerates of talc containing indapamide by crystallo-co-agglomeration technique. Hydroxypropyl methylcellulose 15 cps and polyethylene glycol 6000 were used to impart the desired sphericity, strength, and deformability to agglomerates, respectively. Ethyl cellulose 10 cps was used to improve the strength of agglomerates and achieve extended release. Design of experiment (rotatable central composite design) was implemented for the elucidation of the effect of type and quantity of polymers on quality attributes of agglomerates. Prepared agglomerates were evaluated for morphological, micromeritic, mechanical, and drug release properties. A satisfactory yield (> 97%, wt/wt), better crushing strength, and low friability of agglomerates indicated good processing and handling characteristics. Compatibility and reduced crystallinity of indapamide in agglomerates were confirmed by spectroscopic and X-ray diffraction studies. Formation of the miniscular dosage form and hydrophobicity of talc were the key factors observed in controlling and extending the drug release (up to 6 h) from agglomerates. Hence, the developed crystallo-co-agglomeration technique could be successfully used for the preparation of directly compressible high-strength extended-release spherical agglomerates of indapamide.

In vitro studies of the anticancer action of Tectaria cicutaria in human cancer cell lines: G0/G1 p53-associated cell cycle arrest-Part I.

OBJECTIVE: The rhizome of Tectaria cicutaria has been used in Indian traditional medicine for the treatment of various disorders. The objective of present investigation is to screen various extracts of the rhizomes of Tectaria cicutaria for anti-cancer activity and to investigate the mechanism involved. MATERIALS AND METHODS: The rhizomes of Tectaria cicutaria were extracted with different solvents. In vitro anti-cancer activity of different rhizome extracts were studied in Human cancer Cell Lines using Sulphorodamine B (SRB) colorimetric cytotoxicity assay. The effect of ethanolic extract (TCe) on cell growth inhibition, modulation in gene expression, and induction of apoptosis using the K562 human leukemia cell line were studied. The extract was analyzed by GC-MS to identify their major chemical compounds. RESULTS: TCe shows antioxidant potential in both DPPH scavenging assay and reducing capacity. Flow cytometric analysis showed that 11 µg/ml of TCe arrested cell cycle progression at the G0/G1 phase. In the TCe treated K562 cells, the mRNA and protein expression level of p53 was strongly up-regulated in reverse transcription polymerase chain reaction. Furthermore, its downstream target p21 level was also increased. The GC-MS study has depicted results with the presence of twelve different compounds which will require significant further efforts for structure and putative identification. CONCLUSION: The present work has for the first time, tried to elucidate the anti leukemic potential of Tectaria cicutaria. TCe was more potent in K562 cells, altering the cell cycle progression and inducing apoptosis.

Colon targeted curcumin microspheres laden with ascorbic acid for bioavailability enhancement.

An objective of the present study was to prepare colon-specific microspheres of curcumin (CUR) containing ascorbic acid (AA) for improved oral bioavailability. 32 factorial design was used to optimise chitosan microspheres (CSMS) containing CUR and AA. Subsequently, optimised CSMS were coated with Eudragit S-100, for delivery to colon. In vitro drug release, in vivo pharmacokinetics, and organ distribution studies were performed in Albino Wistar rats. Stabilisation of CUR in alkaline pH was successfully guarded by AA to the extent 98.5-100%. Results revealed complete amorphisation/molecular dispersion of CUR. Bioavailability enhancement of CUR and 90% of MS in colon at the end of 8 h in animals, deciphered successful design of colon-specific CUR MS. It can be concluded that AA in MS shielded the degradation of CUR. The developed double coat MS could be considered as a promising colon-targeted system for CUR aiming bioavailability enhancements.

Screening of drug-sericin solid dispersions for improved solubility and dissolution.

The aim of present attempt deals with preparation of binary dispersion of sericin, waste of sericulture industry in order to enhance solubility and dissolution of poorly soluble drugs. Solid dispersions (SDs) of BCS-II drugs were prepared by spray drying, solvent evaporation, ball milling and physical mixing in ratio of drug:sericin (1:0.5, 1:1, 1:1.5, 1:2, 1:2.5 and 1:3). Further, SDs were investigated by solubility, ATR-FTIR, XRD, DSC, micromeritics and tablettability, surface morphology and in-vitro dissolution. Results demonstrated that, sericin improves solubility of drugs by 8-10 fold. The ATR-FTIR showed the slight shifting/broadening of principle peaks corresponding to NH and OH. Spray dried (1:2w/w) SDs showed maximum reduction in crystallinity of drugs indicating drug was molecularly distributed and was in amorphous state. Spray dried SDs of meloxicam showed better compressibility and compactibility. The microphotograph of spray dried SDs of lornoxicam and meloxicam showed bowl shaped and blend of bowl and spherical particles respectively, while spray dried SDs of felodepine showed spherical shape. The spray dried SDs (1:2w/w) displayed better dissolution performance than other methods Conclusively, sericin offers a hydrophilic matrix to deliver poor water soluble drugs and its aerodynamic shape may show a great potential for various drug deliveries.

Phytochemicals Formulated As Nanoparticles: Inventions, Recent Patents and Future Prospects.

BACKGROUND: The quest to improve the therapeutic effectiveness of herbal drugs has driven the pharmaceutical research towards the development of herbal nanoparticles. OBJECTIVE: Till date, various approaches have been adopted for the design of herbal nanoparticles. METHODS: We carried out an organized search of bibliographic databases consisting of an ample number of published abstracts and research articles using a focused review questionaries and insertion/ omission criteria. The study was systematically structured to review various phytochemicals formulated as nanoparticles, understand its need and prospects. Indeed, research cited has revealed revival of some phytochemicals with therapeutic efficacy fronts. RESULTS: Certain patents (US20170157005A1, US20160228362A1 and US20150050357A1) have evinced entrapment concerns of phytoceuticals into nanoparticles. Amongst various phytochemicals, Curcumin, Quercetin, Silymarin, Paclitaxel etc. seems predominant ones being successfully formulated as nanoparticles. The reason for the availability of their splendid formulations lies in the addresal of poor stability, poor water solubility and consequently poor bioavailability. CONCLUSION: If bioavailability constraint is overcome, diseases like cancer, Alzheimer's, diabetes, liver disorder etc. can be effectively targeted. By doing so, the largely affected society, will breathe the relief. The present article is an attempt to elaborate and conclude on how nanoparticles have been serving as a tool to enhance the effectiveness of phytochemicals, by solubilization, dissolution and consequent bioavailability enhancements, along with in vivo targeting. To further facilitate understanding, the review discusses disease/disorder and phytochemicals with focus on their nanoparticles.

Enhancement in in vitro anti-angiogenesis activity and cytotoxicity in lung cancer cell by pectin-PVP based curcumin particulates.

The aim of this work was to prepare pectin-poly (vinyl pyrrolidone) [PVP] based curcumin particulates to enhance the anticancer potential of curcumin, solubility and allow its localized controlled release. Pectin-PVP based curcumin particulates (PECTIN-PVP CUR) were prepared by spray drying technique in different ratios and were evaluated for surface morphology, micromeritics, flowability, particle size, drug content, in vitro dissolution, inhalable fraction, anti-angiogenesis/angiolysis and cytotoxicity. Results of micromeritic properties, Carr's index, Hausner's ratio and angle of repose were satisfactory. The batch CP3 was considered as optimum, due to excellent flowability, acceptable aggregation and enhanced solubility. The particle size and size distribution data of selected batch CP3 showed 90% of curcumin particulates having size less than 2.74µm, which may deposit to lungs. Twin Impinger studies showed that 29% of respirable fraction was generated, which could be directly delivered to lungs. The in vitro dissolution data showed many fold increase in dissolution rate. Angiolytic activity and MTT assay of PECTIN-PVP CUR have demonstrated enhancement in the anti-tumor potential, compared to curcumin alone. Altogether, PECTIN-PVP CUR were found suitable for local delivery and enhance its anticancer potential of curcumin.

Enhanced dissolution and bioavailability of Nateglinide by microenvironmental pH-regulated ternary solid dispersion: in-vitro and in-vivo evaluation.

OBJECTIVES: Nateglinide, an Antidiabetic drug (BCS II), shows pH-dependent solubility and variable bioavailability. The purpose of study was to increase dissolution and bioavailability of Nateglinide by development of its microenvironmental pH-regulated ternary solid dispersion (MeSD). METHODS: MeSD formulation of Nateglinide, poloxamer-188 and Na2 CO3 was prepared by melt dispersion in 1 : 2 : 0.2 w/w ratio and further characterised for solubility, In-vitro dissolution, microenvironmental pH, crystallinity/amorphism, physicochemical interactions, bioavailability in Wistar rats. KEY FINDINGS: Solubility of Nateglinide was increased notably in MeSD, and its in-vitro dissolution study showed fourfold increase in the dissolution, particularly in 1.2 pH buffer. Prominent reduction in the peak intensity of X-ray powder diffraction (XRPD) and absence of endotherm in DSC thermogram confirmed the amorphism of Nateglinide in MeSD. Attenuated total reflectance Fourier transform infrared spectra revealed the hydrogen bond interactions between Nateglinide and poloxamer-188. In-vivo study indicated that MeSD exhibited fourfold increase in area under curve over Nateglinide. Tmax of MeSD was observed at 0.25 h, which is beneficial for efficient management of postprandial sugar. Instead of mere transformation of the Nateglinide to its amorphous form as evidenced by DSC and XRPD, formation of a soluble carboxylate compound of Nateglinide in MeSD was predominantly responsible for dissolution and bioavailability enhancement. CONCLUSIONS: The study demonstrates the utility of MeSD in achieving pH-independent dissolution, reduced Tmax and enhanced bioavailability of Nateglinide.