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.

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.

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.

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.

Development and characterization of gelatin based nanoparticles for targeted delivery of zidovudine.

INTRODUCTION: The present work was aimed at development and evaluation of zidovudin (AZT) loaded gelatin nanoparticles (GNPs) by simple desolvation method and further couple it with mannose. MATERIAL AND METHODS: Total seven batches of GNPs (A1-A7) were formulated by changing the concentration of polymer gelatin. Various parameters such as particle size, polydispersity index, zeta potential, % entrapment efficiency and in-vitro drug release of plain and mannosylated gelatin nanoparticles (M-GNPs) were studied. RESULTS: Scanning electron microscopy (SEM) studies revealed that the average particle size of GNPs and M-GNPs were found to be 394 ± 3.21 and 797.2 ± 2.89 nm respectively (optimised batch A3). It was interesting to note that the average particle size of M-GNPs was more due to anchored mannose, whereas drug entrapment was lesser compared to plain GNPs. Studies have showed drug loading for GNPs and M-GNPs to be 66.56% and 58.85% respectively. Zeta potential studies demonstrated little reduction in solution stability of M-GNPs compared to GNPs. In-vitro drug release studies showed almost 80% release (bimodal) up to 24 h, following Korsmeyer-Peppas release kinetics model (GNPs, r = 0.9760; M-GNPs, r = 0.9712). CONCLUSIONS: Hence, it can be concluded that, development of GNPs and M-GNPs will pave the way for reticuloendothelial system uptake of AZT; thus, achieving targeted delivery, selectivity and reduction in associated side effect reduction in acquired immuno defficiency syndrome.

Solid-state characterization and dissolution properties of meloxicam-moringa coagulant-PVP ternary solid dispersions.

The effect of ternary solid dispersions of poor water-soluble NSAID meloxicam with moringa coagulant (obtained by salt extraction of moringa seeds) and polyvinylpyrrolidone on the in vitro dissolution properties has been investigated. Binary (meloxicam-moringa and meloxicam-polyvinylpyrrolidone (PVP)) and ternary (meloxicam-moringa-PVP) systems were prepared by physical kneading and ball milling and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffractometry. The in vitro dissolution behavior of meloxicam from the different products was evaluated by means of United States Pharmacopeia type II dissolution apparatus. The results of solid-state studies indicated the presence of strong interactions between meloxicam, moringa, and PVP which were of totally amorphous nature. All ternary combinations were significantly more effective than the corresponding binary systems in improving the dissolution rate of meloxicam. The best performance in this respect was given by the ternary combination employing meloxicam-moringa-PVP ratio of [1:(3:1)] prepared by ball milling, with about six times increase in percent dissolution rate, whereas meloxicam-moringa (1:3) and meloxicam-PVP (1:4) prepared by ball milling improved dissolution of meloxicam by almost 3- and 2.5-folds, respectively. The achieved excellent dissolution enhancement of meloxicam in the ternary systems was attributed to the combined effects of impartation of hydrophilic characteristic by PVP, as well as to the synergistic interaction between moringa and PVP.

Preparation and evaluation of talc agglomerates obtained by wet spherical agglomeration as a substrate for coating.

The present research was aimed at the preparation of spherical agglomerates of talc (SAT) by wet spherical agglomeration (WSA) and evaluation as inert core/substrate for coating. Talc being an inert and inexpensive excipient was used in the design of spherical agglomerates. To evaluate agglomerate performance, comparison was made with sugar spheres (SS), having a size 1200 µm, for surface morphology, micromeritics, mechanical, compressional and drug release properties. Surface morphology studied by scanning electron microscopy (SEM) and optical profilometry have shown smooth surface of SAT compared to SS. Shape and sphericity analysis of both showed aspect ratio close to 1. Flowability of SAT was similar to SS. Although, crushing force of SAT was significantly less than SS (p = 0.05), friability studies revealed that it was satisfactory. Compressibility studies showed plastic deformation of SAT unlike SS. Both SAT and SS had comparable drug and polymer layering efficiency, with better surface smoothness in SAT than SS, as confirmed from optical profilometry. Thus, SAT, similar to SS, can be used as a substrate for coating due to its comparable surface topography, micromeritics, adequate crushing resistance and satisfactory drug and polymer layering efficiency.