21 research outputs found
Development of self-nanoemulsifying tablet (SNET) for bioavailability enhancement of sertraline
No full textAbstract The purpose of the study was to combine the advantages of self-nanoemulsifying drug delivery systems and tablets as a conventional dosage form. Self-nanoemulsifying drug delivery system (SNEDDS) was prepared to enhance the solubility and thus oral bioavailability of sertraline. Aqueous titration method was used to prepare the liquid SNEDDS; ternary phase diagrams were constructed and based on smaller droplet size (24.8 nm), minimum viscosity (153.63 cP) and polydispersity index (0.182), higher percentage transmittance (95%) and in vitro drug release (97%), an optimum system was designated. Liquid SNEDDS was transformed into free-flowing powder by solid adsorption technique followed by compression into tablets. In vitro release of sertraline from liquid and solid SNEDDS was found to be highly significant compared to plain sertraline (p<0.01). Pharmacokinetic studies after oral administration of liquid and solid SNEDDS in rats showed about 6-and 5-fold increased absorption of sertraline compared to the aqueous suspension of sertraline. These studies demonstrate that the solid SNEDDS are promising strategies for successful delivery of poorly water-soluble drug like sertraline
Spray-dried nanoemulsion for improved oral delivery of silymarin against hepatic cancer cells: silymarin against hepatic cancer cell
No full textSilymarin recognized for numerous activities, but the use is limited due to poor aqueous solubility, inefficient intestinal permeability, and low-erratic bioavailability. The aim of the current research was formulation of spray-dried nanoemulsion to enhance the solubility of silymarin. The nanoemulsion was prepared by aqueous titration method, spray died and characterized for thermal analysis by diffraction scanning calorimetry, crystallography analysis by x-ray diffraction, surface morphology by scanning electron microscopy. The reconstitution properties were determining for droplet size, polydispersity index and microscopic structure. Optimized nanoemulsion composed of 15% v/v of oil, 33% v/v of Smix and 52% v/v of distilled water demonstrated lowest droplet size (52.4 ± 1.63 nm) and polydispersity index (0.112), optimum viscosity (23.37 ± 2.36 cps), maximum % transmittance (94.55), optimum cloud point (88°C) and cumulative % drug release (98.43%). The microscopic structure of spray-dried nanoemulsion after reconstitution in distilled water revealed spherical shape free from any aggregation. Spray-dried nanoemulsion demonstrated amorphous sate of silymarin after fabrication into solid state. The cumulative % release of silymarin was significantly higher than marketed conventional suspension (Limarin). The developed spray-dried nanoemulsion was robust and stable for a period of 3 months that could be recommended for oral administration of silymarin after further study. Solids are preferred over liquid dosage form; the formulation may offer better patient compliance over liquid nanoemulsion. In addition, the in-vitro cytotoxicity study revealed more cytotoxicity of SD-NE than plain silymarin against HepG2 cell line after 48 h of incubation. Moreover, the HepG2 cellular uptake silymarin was found to be substantially higher from NE when compared to the plain silymarin. Further, silymarin loaded SD-NE could be potential approach against hepatic cancer.
Keywords: Silymarin, spray-dried nanoemulsion, dextran, phase diagram, solubility, stabilit
In vitro/in vivo performance of different complexes of itraconazole used in the treatment of vaginal candidiasis
No full textA large majority of new chemical entities and many existing drug molecules exhibit poor aqueous solubility, which may limit their potential use in developing drug formulations, with optimum bioavailability. One of the approaches to improve the solubility of a poorly water soluble drug and eventually its bioavailability is complexation with agents like humic acid (HA), fulvic acid (FA), β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and caffeine (Caff). The current work emphasized at employing these agents to prepare different complexes and their in vitro/in vivo assessment. All the complexes evaluated for their complexation efficiency and authenticated by molecular modeling; conformational analysis, differential scanning calorimetry (DSC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and mass spectroscopy. Furthermore, the complexes were assessed in an in vivo, rat vaginal model for their efficacy in treatment of vaginal candidiasis. Amongst the five tested complexes, fulvic acid-itraconazole complex yielded better solubility as well as in vivo efficacy and therefore may further be explored for developing a commercial formulation for treating vaginal candidiasis.A maioria das novas entidades químicas e muitas moléculas de fármacos existentes apresenta fraca solubilidade em água, o que pode limitar seu uso potencial no desenvolvimento de formulações com biodisponibilidade ideal. Uma das abordagens para melhorar a solubilidade de um fármaco pouco solúvel em água e, eventualmente, a sua biodisponibilidade é a complexação com agentes como o ácido húmico (HA), ácido fúlvico (FA), β-ciclodextrina (β-CD), 2-hidroxipropil-β-ciclodextrina (HP-β-CD) e cafeína (Caff). O presente trabalho baseia-se no uso desses agentes para preparar diferentes complexos e suas avaliações in vitro/in vivo. Todos os complexos foram avaliados quanto à eficiência de complexação por modelação molecular, análise conformacional, calorimetria de varredura diferencial (DSC), difração de raios-X (XRD), ressonância magnética nuclear (RMN) e espectroscopia de massas. Além disso, os complexos foram avaliados in vivo, em ratas, no tocante à sua eficácia no tratamento de candidíase vaginal. Entre os cinco complexos testados, o complexo de ácido fúlvico-itraconazol foi o que apresentou melhor solubilidade, bem como melhor eficácia in vivo e, portanto, pode ser explorado para o desenvolvimento de uma formulação comercial para o tratamento de candidíase vaginal
Development of Nanogel Loaded with Lidocaine for Wound-Healing: Illustration of Improved Drug Deposition and Skin Safety Analysis
No full textA wound refers to a cut or blow that may result in primary or secondary infection or even death, if untreated. In the current study, we have explored the wound-healing properties of lidocaine nanogel, owing to its antioxidant and neutrophilic modulatory potential. Initially, the pre-formulation study was performed and then using central composite design (CCD) fabrication and the characterization of lidocaine-loaded nanoemulsion was carried out. After the preparation of a nanogel of lidocaine-loaded nanoemulsion, it was evaluated on various parameters, such as pH, spreadability, extrudability, drug content, in vitro drug release, dermatokinetic study and in vivo skin safety. Based on the pre-formulation study, the maximum solubility of lidocaine was found in oleic acid (324.41 ± 4.19 mg/mL) and in Tween 20 (192.05 ± 8.25 mg/mL), selected as a suitable emulsifier. The refractive index of the optimized nanoemulsion was found to be 1.35 ± 0.04, the electrokinetic potential was recorded as −15.47 ± 0.95 mV. The pH, spreadability and extrudability of nanogel was found to be 6.87 ± 0.51, 73.32 ± 4.59 gm.cm/sec and 107.41 ± 6.42 gm/cm(2), respectively. The percentage of the cumulative drug content and drug release from nanogel was found to be 99.94 ± 1.70% and 93.00 ± 4.67%, respectively. Moreover, dermatokinetic study showed significantly (p < 0.0005) improved drug deposition and the in vivo skin safety study showed no sign of dermal erythematous lesion or any visible damage. Stability studies also testified the secureness of nanogel after storage in a prescribed environmental condition. Thus, this study provides substantial evidence for healing wounds effectively and the further evaluation of the in vivo model. The patent related to this work was published in the Indian Official Journal of the Patent Office (Issue number: 20/2022)
Intravenous Nanocarrier for Improved Efficacy of Quercetin and Curcumin against Breast Cancer Cells: Development and Comparison of Single and Dual Drug–Loaded Formulations Using Hemolysis, Cytotoxicity and Cellular Uptake Studies
No full textThe present work highlights the suitability of an oil-based nanocarrier to deliver quercetin (Q) and curcumin (C) through the intravenous route for treatment of breast cancer. The nanoemulsion prepared by the modified emulsification-solvent evaporation method resulted in particle size (<30 nm), polydispersity index (<0.2), zeta potential (<10 mV), optimum viscosity, high encapsulation efficiency and drug loading for both drugs. The pH and osmolarity of the nanoemulsion were about 7.0 and 280 mOsm, respectively, demonstrated its suitability for intravenous administration. In-vitro release of drugs from all the formulations demonstrated initial fast release followed by sustained release for a period of 48 h. The fabricated single and dual drug–loaded nanoemulsion (QNE, CNE, QC-NE) exhibited moderate hemolysis at a concentration of 50 μg/mL. The % hemolysis caused by all the formulations was similar to their individual components (p ˃ 0.05) and demonstrated the biocompatibility of the nanoemulsion with human blood. In vitro cytotoxic potential of single and dual drug–loaded nanoemulsions were determined against breast cancer cells (MF-7). The IC(50) value for QNE and CNE were found to be 40.2 ± 2.34 µM and 28.12 ± 2.07 µM, respectively. The IC(50) value for QC-NE was 21.23 ± 2.16 µM and demonstrated the synergistic effect of both the drugs. The internalization of the drug inside MF-7 cells was detected by cellular uptake study. The cellular uptake of QNE and CNE was approximately 3.9-fold higher than free quercetin and curcumin (p < 0.0001). This strategically designed nanoemulsion appears to be a promising drug delivery system for the proficient primary preclinical development of quercetin and curcumin as therapeutic modalities for the treatment of breast cancer
Novel Therapeutic Approach in PEGylated Chitosan Nanoparticles of Apigenin for the Treatment of Cancer via Oral Nanomedicine
No full textThe goal of this study was to optimize and formulate apigenin (APG)-loaded pegylated chitosan nanoparticles (PEGylated-CNPs) via ionic gelation techniques using the Box–Behnken design (BBD). Three individual variables, X1(chitosan: TPP concentration), X2 (PEG-400 concentration), and X3 (sonication time), were investigated for their influence on response variables (Y1—particle size (PS); Y2—drug entrapment efficiency (DEE); and Y3—zeta potential (ZP). The optimized formula of APG-PEGylated CNPs was picked from the statistical design and was then examined for physical, morphological, release characterization, anti-oxidant, and anti-tumor potential. The average PS, PDI, %DEE, and ZP were found to be 139.63 ± 5.67 nm, 0.296 ± 0.014, 79.55 ± 3.12%, and 24.68 ± 1.84 mV, respectively. The optimized APG formulation was chosen and reformulated based on the desirability function. Results of the observed and predicted values of responses through the BBD process were found to be nearly identical. The resulting APG-PEGylated CNPs were spherical and smooth, according to surface morphology studies. The release study revealed that PEGylated-CNPs exhibited biphasic release patterns distinguished by an initial burst release of APG only at early phases accompanied by a delayed release near 24 h. Furthermore, APG-PEGylated CNPs demonstrated statistically increased antioxidant activities and cytotoxicity against MCF-7 cells compared to pure APG. Based on the findings, it is possible to conclude that BBD was efficient in optimizing the PEGylated CNPs formulation and recognizing the impacts of formulation variables. In conclusion, the developed formulation has a significant potential for anticancer therapy
Green Synthesis of Oxoquinoline-1(2H)-Carboxamide as Antiproliferative and Antioxidant Agents: An Experimental and In-Silico Approach to High Altitude Related Disorders
No full textAt high altitudes, drops in oxygen concentration result in the creation of reactive oxygen and nitrogen species (RONS), which cause a variety of health concerns. We addressed these health concerns and reported the synthesis, characterization, and biological activities of a series of 10 oxoquinolines. N-Aryl-7-hydroxy-4-methyl-2-oxoquinoline-1(2H)carboxamides (5a–j) were accessed in two steps under ultrasonicated irradiation, as per the reported method. The anticancer activity was tested at 10 µM against a total of 5 dozen cancer cell lines obtained from nine distinct panels, as per the National Cancer Institute (NCI US) protocol. The compounds 5a (TK-10 (renal cancer); %GI = 82.90) and 5j (CCRF-CEM (Leukemia); %GI = 58.61) showed the most promising anticancer activity. Compound 5a also demonstrated promising DPPH free radical scavenging activity with an IC50 value of 14.16 ± 0.42 µM. The epidermal growth factor receptor (EGFR) and carbonic anhydrase (CA), two prospective cancer inhibitor targets, were used in the molecular docking studies. Molecular docking studies of ligand 5a (docking score = −8.839) against the active site of EGFR revealed two H-bond interactions with the residues Asp855 and Thr854, whereas ligand 5a (docking = −5.337) interacted with three H-bond with the residues Gln92, Gln67, and Thr200 against the active site CA. The reported compounds exhibited significant anticancer and antioxidant activities, as well as displayed significant inhibition against cancer targets, EGFR and CA, in the molecular docking studies. The current discovery may aid in the development of novel compounds for the treatment of cancer and oxidative stress, and other high altitude-related disorders
Solvent Extraction and Gas Chromatography–Mass Spectrometry Analysis of <i>Annona squamosa</i> L. Seeds for Determination of Bioactives, Fatty Acid/Fatty Oil Composition, and Antioxidant Activity
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