COLON SPECIFIC DELIVERY OF COMBINATION OF 5-FLUOROURACIL AND CELECOXIB: PREPARATION, CHARACTERIZATION, AND IN VITRO CYTOTOXICITY ASSAY

Objective: 5-Fluorouracil (5-FU) and celecoxib (Cel) combination offered additive effect in the treatment of colon cancer. However, physicochemical and biopharmaceutical attributes of both drugs deliver suboptimal concentration at the site of action. The objective of the current study is the development of a microparticulate drug delivery system loaded with a combination of 5-FU and Cel to achieve prolonged drug delivery in colon cancer. Methods: 5-FU and Cel combination were loaded in Eudragit coated chitosan (CH) microspheres (MSs) and characterized. Results: The average particle size of the MSs was in the range of 2.7±0.9μm to 4.8±1.1μm. A substantial drug encapsulation efficiency of 71.30±2.3% as obtained for 5-FU as compared to 35.20±1.9% of Cel in the tailored microparticles. The drug loading capacity of 6.5 mg/10 mg and 2.3 mg/10 mg was obtained for 5-FU and Cel, respectively. By Eudragit S 100 (Ed) coating, significant pH-dependent release profile was achieved, and no drug release was observed in simulated gastric and intestinal fluids. The developed MSs exhibited the release of 92.1±2.9% of 5-FU in 8h whereas 18.9±0.7% Cel was found to be released from the developed MSs. The drug-loaded MSs exhibited appreciable potency against HT-29 cells with an IC50 value of 35.9 μM. Conclusion: The results indicated that these microparticles are a promising vehicle for selectively targeting drugs to the colon in the chemotherapy of colon cancer

Telmisartan loaded Solid Lipid Nanoparticles augmented cytotxicity in cervical cancer cells: Optimization and in vitro characterization

Cervical cancer, a malignant cancer is leading second most cancer found in women. Telmisartan has 3000 times more affinity toward angiotensin II receptor type 1 (AT1) receptor than AT2 and inhibited neovascularization by down-regulating VEGF acting on endothelial cells with antagonized activity of Angiotensin II. Despite well-known therapeutic potential of telmisartan in malignant cancer, poor physicochemical properties and pharmacokinetic properties including meageraqueous solubility (0.078 mg/mL), low oral bioavailability (45-58%), and erratic biodistribution not only limit the therapeutic potential of telmisartan in treatment of malignant cancer but also appeal for development of dosage form with enhanced oral bioavailability.  Telmisartan encapsulated stearic acid nanostructured solid lipid particles were developed by solvent diffusion method. On applying of box behnken design with three factors and three levels, 17 different formulations were yielded and prepared with Response of particle size (Y1) and percentage drug entrapment (Y2) for 17 formulations were evaluated. The IC50 value of optimized telmisartan loaded lipid nanoparticle and market preparation, indicated telmisartan loaded solid lipid nanoparticle expressed lower IC50 value of 30.28 μM with significant anticancer activity against HeLa cancer cell line in comparison to higher IC50 value 58.69 μM of market preparation. In conclusion, telmisartan loaded solid lipid nanoparticles may be a promising drug delivery systems for cervical cancer. Keywords: Telmisarn, cervical cancer; solid lipid nanoparticles; cytotxicit

Telmisartan-poly (ethylene glycol) conjugate augmented drug dissolution and permeability in cervical cancer cells

Telmisartan is currently reported for inhibiting cervical cancer cells. Despite favorable therapeutic profile, poor aqueous solubility and low oral bioavailability limit its therapeutic application in treatment of cervical cancer. Telmisartan was chemically conjugated to poly (ethylene glycol) through amide linkage to form telmisartan-PEG drug conjugate. Poly (ethylene glycol) with terminal –NH2 was conjugated with telmisartan via amide linkage. Telmisartan-PEG conjugate displayed peak at 1690 cm-1 for C=O group of amide linkage. Furthermore, telmisartan illustrated the crystalline lattice as compared to amorphous nature of telmisartan-PEG conjugate. The in vitro dissolution testing indicated that telmisartan displayed only 22.6±3.8% drug release from dialysis bag as compared (Two-way ANOVA test, P<0.05) to 76.9±5.4% from telmisartan-PEG conjugate. The therapeutic efficacy of telmisartan and telmisartan-PEG conjugate was analyzed in cervical cancer, HeLa cells. The IC50 of telmisartan in HeLa cells was estimated to be 48.6±6.9µM as compared (Two Way ANOVA test) to 17.2±2.7-µM of telmisartan-PEG conjugate dissolved in aqueous phase. In conclusion, telmisartan-PEG conjugate must be investigated under a set of stringent in vivo parameters for pharmacokinetic and pharmacodynamic studies.  Keywords: Cervical cancer, telmisartan, poly (ethylene glycol), conjugate, dissolution, cytotoxicit

EXTRACTION OF GUM FROM ABELMOSCHUS ESCULENTUS: PHYSICOCHEMICAL PECULIARITY AND ANTIOXIDANT PREPATENT

  Objective: This study is aimed to extract gum from Abelmoschus esculentus using ultrasonic assisted method and exploring physicochemical, functional, and antioxidant potential of gum for food and pharmaceuticals.Materials and Methods: The extraction of gum from okra was done employing ultrasound-assisted method to improvise the yield. The extracted gum was further characterized for physical properties including swelling index, solubility, water sorption time, packing and flow properties, electrical properties, zeta potential, scanning electron microscopy, and antioxidant activity.Results: The extraction yield of okra fruit gum (OFG) was found to be 31.52%±0.22% (n=3). The OFG powder obtained after lyophilization showed good flow properties as determined from the results of angle of repose (34.21°), Hausner ratio (1.14), and % compressibility (12.5%). An increase in solubility and swelling index of OFG with increase in pH of buffer from 2.0 to 7.4 was observed. The freeze dried OFG possess rough surface and zeta potential of −9.85 mV. Application of derivatized/interacted OFG gum for modification of drug release profiles is concluded from high degree of esterification of 7.8.Conclusion: The result suggest that the antioxidant activity of OFG was higher compared to corn flour gum. Thus, OFG could be utilized as natural antioxidant food ingredients and also for application in medicine and health-care products

Cyclodextrin Complexes of Reduced Bromonoscapine in Guar Gum Microspheres Enhance Colonic Drug Delivery

Here, we report improved solubility and enhanced colonic delivery of reduced bromonoscapine (Red-Br-Nos), a cyclic ether brominated analogue of noscapine, upon encapsulation of its cyclodextrin (CD) complexes in bioresponsive guar gum microspheres (GGM). Phase−solubility analysis suggested that Red-Br-Nos complexed with β-CD and methyl-β-CD in a 1:1 stoichiometry, with a stability constant (Kc) of 2.29 × 103 M−1 and 4.27 × 103 M−1. Fourier transforms infrared spectroscopy indicated entrance of an O−CH2 or OCH3−C6H4−OCH3 moiety of Red-Br-Nos in the β-CD or methyl-β- CD cavity. Furthermore, the cage complex of Red-Br-Nos with β-CD and methyl-β-CD was validated by several spectral techniques. Rotating frame Overhauser enhancement spectroscopy revealed that the Ha proton of the OCH3−C6H4−OCH3 moiety was closer to the H5 proton of β-CD and the H3 proton of the methyl-β-CD cavity. The solubility of Red-Br-Nos in phosphate buffer saline (PBS, pH ∼ 7.4) was improved by ∼10.7-fold and ∼21.2-fold when mixed with β-CD and methyl-β-CD, respectively. This increase in solubility led to a favorable decline in the IC50 by ∼2-fold and ∼3-fold for Red-Br-Nos−β-CD-GGM and Red-Br-Nos−methyl-β-CD-GGM formulations respectively, compared to free Red-Br-Nos−β-CD and Red-Br-Nos−methyl-β-CD in human colon HT-29 cells. GGM-bearing drug complex formulations were found to be highly cytotoxic to the HT-29 cell line and further effective with simultaneous continuous release of Red-Br-Nos from microspheres. This is the first study to showing the preparation of drug-complex loaded GGMS for colon delivery of Red-Br-Nos that warrants preclinical assessment for the effective management of colon cancer

Učinak ampicilina i klorokina na humoralnu imunošku reakciju na goveđi albumin kapsuliran u liposome

Immune suppression resulting from chemoprophylaxis and potential drug interaction were investigated in experimental animals pre-medicated with ampicillin and chloroquine followed by immunization with bovine serum albumin bearing liposomes prepared by the reverse phase evaporation method. The prepared liposomes were evaluated for particle size, entrapment efficiency and in vitro release. Humoral immune response was measured in terms of systemic IgG antibody titre by the ELISA method. The present study showed that 7:3 molar ratio of soya phosphatidylcholine and cholesterol produced liposomes of mean diameter of 235.4 10.3 nm and entrapment efficiency of 41.3 3.2%. Ampicillin significantly (p < 0.05) decreased the antibody titre whereas chloroquine did not reduce the antibody titre significantly. The study will help in programming a new drug management and in characterization of vaccine-drug interaction.Na eksperimentalnim životinjama koje su prvo tretirane ampicilinom i klorokinom a zatim imunizirane goveđim serumskim albuminom s liposomima praćena je supresija imunološkog sustava i potencijalna interakcija lijekova. Liposomi su pripravljeni metodom reverzno-fazne evaporacije, a određena im je veličina čestica, količina supstancije koju mogu inkorporirati i oslobađanje in vitro. Humoralna imunološka reakcija praćena je određivanjem titra IgG antitijela ELISA metodom. Rezultati rada pokazuju da liposomi s fosfatidilkolinom iz soje i kolesterolom u molnom omjeru 7:3 imaju prosječni promjer 235.4 10.3 nm i sposobnost inkorporacije 41.3 3.2%. Ampicilin je značajno (p < 0.05) smanjio titar antitijela, a klorokin nije. Ovi će rezultati biti korisni u programiranju novog režima primjene lijekova i u praćenju interakcije između cjepiva i lijeka

PHARMA SCIENCE MONITOR AN INTERNATIONAL JOURNAL OF PHARMACEUTICAL SCIENCES ADVANCEMENT IN TREATMENT TECHNOLOGY FOR UTERINE LEIOMYOMA

ABSTRACT Uterine leiomyomass, or fibroids, represent a major public health problem.This is most common female pelvic tumor, typically reported to occur in 20-40% of reproductive aged women, and up to 70% of white and 80% of black women by the age of 50 years Most fibroids are a symptomatic, but nearly half of women with fibroids have significant and often disabling symptoms including heavy menstrual bleeding, pain and pressure symptoms Traditionally, symptomatic fibroids have been treated with myomectomy or hysterectomy performed by laparotomy In an effort to reduce the cost, morbidity and lifestyle impact of major surgery, various less invasive or non-surgical procedures, new treatment approaches have become available to women with symptomatic fibroids. Undoubtedly the most significant therapeutic innovation has been the advent of uterine artery emobilization (UAE) as a form of non-surgical management. New technology has provided additional minimally invasive options such as percutaneous laser ablation, cryoablation, transvaginal uterine artery occlusion and magnetic resonance imaging (MRI)-guided focused ultrasound that are currently under intense investigation. Furthermore, new medications have been introduced, that show for practical, long-term medical therapy for symptomatic fibroids

APPLICATION OF CENTRAL COMPOSITE DESIGN AND RESPONSE SURFACE METHODOLOGY FOR OPTIMIZATION OF METAL ORGANIC FRAMEWORK: NOVEL CARRIER FOR DRUG DELIVERY

Objective: The aim of the present study is to optimize the synthesis method of metal-organic framework (MOF) for high yield and larger surface area with minimum size for efficient drug loading. Materials and Methods: Materials of Institute Lavoisier (MIL)-101-NH2 was synthesized by microwave-assisted hydrothermal method. Central composite design (CCD) under response surface methodology (RSM) was used for optimization. Process optimization was done by validating the model to obtain maximum surface area, maximum yield, and minimum particle size. Final obtained formulation was characterized by particle size and zeta potential, scanning electron microscopy, powder X-ray diffraction, Fourier-transform infrared spectroscopy, Brunauer–Emmett–Teller, and thermogravimetric analysis. Furthermore, gemcitabine (GEM) was used as a model drug for encapsulation in these MOFs for drug delivery carriers. Results: The results revealed that MIL-101-NH2 of average size-158 nm with high yield (70%) and high surface area (2347 m2/g) could be produced easily and reproducibly at a selected condition. This enhances the drug delivery application of the valuable MIL-101-NH2. Optimized values for these parameters were 170°C, 5.00, and 1:1:400 for temperature, pH, and reactant ratio, respectively. MIL-101-NH2 appeared as a promising carrier for GEM delivery with higher encapsulation (77.7±2%) and loading (22.6±2%). Conclusion: The results conclude that processing parameters such as temperature pH and reactant concentration obtained from CCD-RSM significantly affect the main constraints, i.e., surface area, particle size, and yield. The faster encapsulation of GEM in MOF makes them a promising carrier for drug delivery application

SYNTHESIS AND OPTIMIZATION OF GEMCITABINE-LOADED MIL-101NH2 (Fe) NANOCARRIERS: RESPONSE SURFACE METHODOLOGY APPROACH: GEMCITABINE LOADED MIL-101 NH2 (Fe) NANOCARRIERS

Objective: The objective of the present study is to synthesize and optimize gemcitabine (GEM)-loaded MIL-101NH2 (Fe) nanocarriers. The design of experiments is used to optimize the formulation for higher encapsulation efficiency (EE) for effective drug delivery. Materials and Methods: MIL-101NH2 (Fe) was synthesized by microwave-assisted hydrothermal method. Central composite design (CCD) under response surface methodology was used for the optimization of GEM encapsulation into the MIL-101NH2 (Fe). The most influential variable that affects the EE was investigated by Perturbation plot. Validation of the design was carried out by performing the experiments under optimal conditions. Further optimized formulation was physicochemically characterized for particle size, surface charge, and surface morphology using zetasizer and scanning electron microscopy (SEM), respectively. Structural integrity of the optimized formulation was carried out by Powder X ray crystallography (PXRD). Fourier-transform infrared (FTIR) spectroscopy was used for the confirmation of GEM loading. Accelerated storage stability analysis was also performed to find out the related parameters. Results: Here in this work, crystalline MIL-101NH2 (Fe) has been successfully synthesized by microwave radiation method. The optimization result revealed that process variables such as GEM concentration, pH, and time significantly affect the desired constraint, EE. Perturbation plot evidenced that among all the variables, pH is the most significant factor followed by drug concentration and time. The optimized formulation exhibited 76.4 ± 7% EE and average particle size of 252.9 ± 9.23 nm. PXRD and SEM results demonstrated that the optimized formulation was crystalline in nature. FTIR spectroscopy confirms the presence of drug inside the MIL-101NH2 (Fe). In vitro release profile revealed that MIL-101NH2 (Fe)-GEM exhibited the sustained release up to 72 h in comparison to the native GEM. Storage-stability studies also indicate that MIL-101NH2 (Fe)-GEM has a shelf life of 6 months. Conclusion: The EE of GEM in MIL-101NH2 (Fe) can be altered by varying the drug concentration and pH during the impregnation