Cholesterol derivative-based liposomes for gemcitabine delivery: preparation,in vitro,and in vivo characterization

As an anti-tumor drug, gemcitabine (Gem) is commonly used for the treatment of non-small cell lung cancer and pancreatic cancer. However, there are several clinical drawbacks to using Gem, including its extremely short plasma half-life and side effects. To prolong its half-life and reduce its side effects, we synthesized a derivative of Gem using cholesterol (Chol). This derivative, called gemcitabine-cholesterol (Gem-Chol), was entrapped into liposomes by a thin-film dispersion method. The particle size of the Gem-Chol liposomes was 112.57?±?1.25?nm, the encapsulation efficiency was above 99%, and the drug loading efficiency was about 50%. In vitro studies revealed that the Gem-Chol liposomes showed delayed drug release and long-term stability at 4?°C for up to 2 months. In vivo studies also showed the superiority of the Gem-Chol liposomes, and compared with free Gem, the Gem-Chol liposomes had longer circulation time. Moreover, an anti-tumor study in H₂₂ and S180 tumor models showed that liposomal entrapment of Gem-Chol improved the anti-tumor effect of Gem. This study reports a potential formulation of Gem for clinical application.     

Fluorescent liposomes as contrast agents for in vivo optical imaging of edemas in mice

This study assesses if specially designed fluorescent liposomes can be used as contrast agent for near-infrared fluorescence (NIRF) optical imaging of cultured macrophages in vitro and for NIRF imaging of inflammatory processes, like edema, in an in vivo mouse model. Fluorescent liposomes are prepared by the film hydration and extrusion method using cholesterol, L-phosphatidylcholine, and the NIR fluorescent dye DY-676-C(18) ester. Photon correlation spectroscopy and flow cytometry reveal that fluorescent liposomes are structurally stable for up to 133 days. Distinct uptake/labeling of cultured murine J774 macrophages is demonstrated by confocal laser scanning microscopy (CLSM), flow cytometry, and macroscopic NIRF imaging system at wavelengths >670 nm. Moreover, CLSM analysis reveals fluorescence signals within intracellular compartments. Ear edema is induced in mice (n = 16) by subcutaneous injection of zymosan A. Whole-body NIRF imaging is performed after intravenous injection (0-24 h) of fluorescent liposomes (55 nmol dye per kg body weight). Distinctly higher fluorescence intensities (1613.6 +/- 61.7 a.u.) are detected at inflamed areas of diseased mice as compared to controls (892.8 +/- 19.4 a.u.). Furthermore, cell isolated from ear lavage reveals the presence of labeled F4/80 positive tissue macrophages. Taken together, the results indicate both that mouse macrophages labeled with fluorescent liposomes can be detected in vitro with fluoro-optical methods and that in vivo optical imaging of inflammatory processes with fluorescent liposomes as contrast agent is feasible. Possibly, early stages of other inflammatory diseases could also be detected by the proposed diagnostic tool in the long term.     

The preparation,characterization of Lupeol PEGylated liposome and its functional evaluation in vitro as well as pharmacokinetics in rats

Objective: The objective of this study was to enhance the solubility and bioavailability of Lupeol.

Methods: Utilizing a thin-film dispersion method, we prepared Lupeol-loaded PEGylated liposomes and Lupeol-loaded liposomes, which was characterized using SEM, mean diameter, PDI, zeta potential, and entrapment efficiency (EE). The EE, in vitro release, and stability of Lupeol-loaded PEGylated liposomes were detected using HPLC. In addition to the safety evaluation, the evaluation was carried out on HepG2 cells in vitro; the pharmacokinetics were carried out after i.v. in the rats.

Results: The size, PDI, zeta potential, and EE of Lupeol-loaded PEGylated liposomes and Lupeol-loaded liposomes were 126.9?nm, 0.246, ?1.97?mV, 87%; 97.23?nm, 0.25, 1.6?mV, 86.2%, respectively. Lupeol-loaded PEGylated liposomes showed the slow-release effect in vitro release experiments. Lupeol-loaded PEGylated liposomes offered significant advantages over other experimental groups in vitro studies, such as the highest inhibition rate and the highest apoptosis rate. We also found that Lupeol-loaded PEGylated liposomes blocked cells in the G₂M phase. The pharmacokinetics result showed that the AUC of Lupeol-loaded PEGylated liposomes group was 3.2 times higher than free Lupeol group after i.v., the MRT and t_1/2 values of Lupeol-loaded PEGylated liposomes (MRT = 6.09?h, t_1/2 =12.94?h) showed improvements of 2.5 and 4.1 times compared to free Lupeol (MRT = 2.43?h, t_1/2 = 3.16?h).

Conclusion: The Lupeol-loaded PEGylated liposomes have successfully solved its poor hydrophilicity, low bioavailability.     

Design,preparation, and evaluation of liposomal gel formulations for treatment of acne: in vitro and in vivo studies

The study highlights the significance of co-application of bioactive components into liposomal gel formulations and their comparison to azithromycin for treatment of Acne. A Design of Experiments (DoE) approach was utilized to obtain optimized liposomal formulation encapsulating curcumin, with size and zeta potential of ～100?nm and ～14?mV, respectively, characterized by DLS, HR-TEM, FESEM, and AFM. The curcumin liposomal dispersion depicted excellent stability over the period of 60?days, which was further converted in gel form using Carbopol. Pharmacokinetics of curcumin-loaded liposomal gel showed that T_max for curcumin was achieved within 1?h of post application in both stratum corneum and skin, indicating quick penetration of nano-sized liposomes. Stratum corneum depicted C_max of 688.3?ng/mL and AUC_0-t of 5857.5?h?×?ng/mL, while the skin samples displayed C_max of 203.3?ng/gm and AUC_0-t of 2938.1?h?×?ng/gm. Lauric acid and azithromycin liposomal gel formulations were prepared as per the optimum parameters obtained by DoE. In antibacterial activity using agar diffusion assay, lauric acid gel formulation revealed ～1.5 fold improved antibacterial effect than curcumin gel formulation. Interestingly, their co-application (1:1) exhibited significantly enhanced antibacterial effect against both macrolide-sensitive (1.81 versus 1.25 folds) and resistant strains of P. acnes (2.93 versus 1.22 folds) than their individual counterparts. The in vivo studies in rat ear model displayed a ～2 fold reduction in comedones count and cytokines (TNF-α and IL-1β) on co-application with curcumin and lauric acid liposomal gel compared to placebo treated group.     

Nanosized nasal emulgel of resveratrol: preparation,optimization, in vitro evaluation and in vivo pharmacokinetic study

Abstract

Nano-emulgel has become one of the most significant controlled release systems, which has the advantages of both gels and nano-emulsions. This work aims at the formulation of nasal nano-emulgel for resveratrol, employing carbopol 934 and poloxamer 407 as the gelling agents. The optimum nano-emulsion was determined through further characterization of the selected system. The nasal nano-emulgel was prepared and tested for the in vitro release, the release kinetics, FTIR, ex vivo permeation, nasal mucosa toxicity, and in vivo pharmacokinetic study. The optimum nano-emulsion consisted of Tween 20, Capryol 90, and Transcutol at a ratio of (54.26: 23.81: 21.93%v/v), and it exhibited transmittance of 100%, resveratrol solubility of 159.9?±?6.4?mg/mL, globule size of 30.65?nm. The in vitro resveratrol released from nano-emulsion and nasal nano-emulgel was 96.17?±?4.43% and 78.53?±?4.7%, respectively. Ex vivo permeation was sustained during 12?h up to 63.95?±?4.7%. The histopathological study demonstrated that the formula is safe and tolerable to the nasal mucosa. C_max and AUC _(0–∞) of resveratrol obtained after nasal administration of nasal nano-emulgel was 2.23 and 8.05 times, respectively. Similarly, T_max was increased up to 3.67?±?0.82?h. The optimized nasal nano-emulgel established intranasal safety and bioavailability enhancement so it is considered as a well-designed system to target the brain.     

In vitro and in vivo evaluation of puerarin-loaded PEGylated mesoporous silica nanoparticles

Puerarin, which is extracted from Chinese medicine, is widely used in China and mainly used as a therapeutic agent for the treatment of cardiovascular diseases. Owing to its short elimination half-life in human beings, frequently intravenous administration of high doses of puerarin may be needed, which possibly leads to severe and acute side effects. The development of an effective sustained-release drug delivery system is urgently needed. In this study, PEGylated mesoporous silica nanoparticles (PEG-MSNs) had become a preferred way to prolong the half-life and improve the bioavailability of drugs. The release of puerarin from PEG-MSNs was pH dependent, and the release rate was much faster at lower pH than that at higher pH. Moreover, the PEG-MSNs exhibited improved blood compatibility over the MSNs in terms of low hemolysis, and it could also reduce the side effect of hemolysis induced by PUE. Compared with puerarin, PUE-loaded PEG-MSNs showed a 2.3-fold increase in half-life of puerarin and a 1.47-fold increase in bioavailability. Thus, the PEG-MSNs hold the substantial potential to be further developed as an effective sustained-release drug delivery system.     

Preparation,characterization and in vitro and in vivo evaluation of a solid dispersion of Naringin

Naringin (NA) is one of typical flavanone glycosides widely distributed in nature and possesses several biological activities including antioxidant, anti-inflammatory, and antiapoptotic. The aim of this study was to develop solid dispersion (SD) and to improve the dissolution rate and oral bioavailability of NA. NA–SD was prepared by the traditional preparation methods using PEG6000, F68, or PVP K30 as carrier at different drug to carrier ratios. According to the results of solubility and in vitro dissolution test, the NA–PEG6000 (1:3) SD was considered as an optimal formulation to characterize by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry and powder X-ray diffraction. Furthermore, oral bioavailabilities of NA–PEG6000 (1:3) SD and NA–suspension with the same dosage were investigated in SD rats. The results confirmed the formation of SD and the pharmacokinetic parameters of NA–PEG6000 (1:3) SD (C_max?=?0.645?±?0.262?µg/ml, AUC_0–t?=?0.471?±?0.084?µg/ml?h) were higher than that of NA–suspension (C_max?=?0.328?±?0.183?µg/ml, AUC_0–t =?0.361?±?0.093?µg/ml?h). Based on the results, the SD is considered as a promising approach to enhance the dissolution rate and oral bioavailability of NA.     

Capsaicin pretreatment enhanced the bioavailability of fexofenadine in rats by P-glycoprotein modulation: in vitro,in situ and in vivo evaluation

Background and objective: Capsaicin is the main pungent principle present in chili peppers has been found to possess P-glycoprotein (P-gp) inhibition activity in vitro, which may have the potential to modulate bioavailability of P-gp substrates. Therefore, purpose of this study was to evaluate the effect of capsaicin on intestinal absorption and bioavailability of fexofenadine, a P-gp substrate in rats.

Methods: The mechanistic evaluation was determined by non-everted sac and intestinal perfusion studies to explore the intestinal absorption of fexofenadine. These results were confirmed by an in vivo pharmacokinetic study of oral administered fexofenadine in rats.

Results: The intestinal transport and apparent permeability (P_app) of fexofenadine were increased significantly by 2.8 and 2.6 fold, respectively, in ileum of capsaicin treated rats when compared to control group. Similarly, absorption rate constant (K_a), fraction absorbed (F_ab) and effective permeability (P_eff) of fexofenadine were increased significantly by 2.8, 2.9 and 3.4 fold, respectively, in ileum of rats pretreated with capsaicin when compared to control group. In addition, maximum plasma concentration (C_max) and area under the concentration-time curve (AUC) were increased significantly by 2.3 and 2.4 fold, respectively, in rats pretreated with capsaicin as compared to control group. Furthermore, obtained results in rats pretreated with capsaicin were comparable to verapamil (positive control) treated rats.

Conclusions: Capsaicin pretreatment significantly enhanced the intestinal absorption and bioavailability of fexofenadine in rats likely by inhibition of P-gp mediated cellular efflux, suggesting that the combined use of capsaicin with P-gp substrates may require close monitoring for potential drug interactions.     

Mucoadhesive liposomes as ocular delivery system: physical,microbiological, and in vivo assessment

Background: Mucoadhesive drug delivery is a promising strategy to overcome ocular biopharmaceutical constraints. Objective and methods: Ciprofloxacin HCl-loaded reverse phase evaporation liposomes were coated with different concentrations and molecular weights of mucoadhesive biocompatible chitosan polymer to form chitosomes. This colloidal mucoadhesive system was evaluated in vitro and in vivo with respect to deliver the antibiotic to ocular surface. Results and conclusion: The results obtained pointed out that liposome coating process resulted in entrapment efficiency reduction and higher chitosan concentration, and molecular weight showed a more pronounced effect. No morphological differences between coated and uncoated liposomes were observed. Diffusion was the drug release mechanism from chitosomes. Concerning rheological behavior, pseudoplastic flow was characteristic to the prepared chitosomal dispersions. In addition, chitosan coating improved the ocular permeation of ciprofloxacin HCl. Microbiologically; this formulated system enhanced antimicrobial activity of ciprofloxacin HCl against both Gram-positive and Gram-negative bacteria. Moreover, this mucoadhesive system was able to inhibit the growth of Pseudomonas aeruginosa in rabbits' eyes for 24 hours when compared to the marketed preparation. In vivo bacterial conjunctivitis model elucidated that symptoms were controlled by the prolonged release formulation such as that done by the marketed product.     

Novel naproxen/esomeprazole magnesium compound pellets based on acid-independent mechanism: in vitro and in vivo evaluation

The purpose of this study was to develop the novel naproxen/esomeprazole magnesium compound pellets (novel-NAP/EMZ) depending on EMZ acid-independent mechanism which has been proved to be predominate in the mechanism of co-therapy with nonsteroidal anti-inflammatory drug. The novel-NAP/EMZ compound pellets, composed of NAP colon-specific pellets (NAP-CSPs) and EMZ modified-release pellets (EMZ-MRPs), were prepared by fluid-bed coating technology with desired in vitro release profiles. The resulting pellets were filled into hard gelatin capsules for in vivo evaluation in rats and compared with the reference compound pellets, consisted of NAP enteric-coated pellets (NAP-ECPs) and EMZ immediate-release pellets (EMZ-IRPs). The reference compound pellets were prepared simulating the drug delivery system of VIMOVO^®. In vivo pharmacokinetics, EMZ-MRPs had significantly larger AUC_0–t (p?0–_t. Compared to the reference compound pellets, the novel-NAP/EMZ compound pellets did not show distinct differences in histological mucosal morphology. However, biochemical tests exhibited enhanced total antioxidant capacity, increased nitric oxide content and reduced malondialdehyde level for novel-NAP/EMZ compound pellets, indicating that the acid-independent action took effect. The gastric pH values of novel-NAP/EMZ compound pellets were at a low and stable level, which could ensure normal physiological range of human gastric pH. As a result, the novel-NAP/EMZ compound pellets may be a more suitable formulation with potential advantages by improving bioavailability of drug and further reducing undesirable gastrointestinal damages.     

Piroxicam encapsulated in liposomes: characterization and in vivo evaluation of topical anti-inflammatory effect

Liposomes of soya phosphatidylcholine, cholesterol, and stearylamine (molar ratio 6/3/1) and 0.1% alpha-tocopherol were prepared by the extrusion of multilamellar vesicles through 0.2-micron polycarbonate membrane. Liposomes were characterized by electron transmission microscopy, and the mean structure diameter was 278 nm. The encapsulation efficiency obtained was 12.73%. The topical anti-inflammatory effect was evaluated in vivo by the cotton pellet granuloma method. We analyzed free piroxicam at 4 mg/kg, piroxicam encapsulated in liposomes added to 1.5% hydroxyethylcellulose (HEC) gel at 1.6 mg/kg, and piroxicam encapsulated in liposomes added to HEC gel at 4 mg/kg; the inhibition of inflammation obtained was 21.1%, 32.8%, and 47.4%, respectively. These results showed that the encapsulation of piroxicam produced an increase of topical anti-inflammatory effect, suggesting that the inhibition of inflammation can be obtained with lower drug concentrations.     

In vitro and in vivo evaluation of controlled-release matrix tablets of highly water-soluble drug applying different mw polyethylene oxides (PEO) as retardants

The aim of the work presented is to prepare a controlled-release hydrophilic matrix tablet (CMT) controlling release of highly water-soluble drug applying pure combination of high- and low-Mw PEO as matrix materials, to avoid the lag time of drug release, and to overcome incomplete release in later stages. The influences of types and amounts of different Mw PEOs used, drug loading, pH of release medium and agitation rate on drug release were evaluated. The study of uptake and erosion of matrix was conducted and mechanism of improving drug release was discussed. In vivo pharmacokinetics of the CMT and reference preparation self-made controlled-release osmotic pump tablets (COPT) were performed in beagle dogs. The optimized formulation containing 43% PEO WSR 303 and 32% PEO N750 showed a zero order release from 1?h to 12?h. In vivo results demonstrated that the CMT had similar AUC_0-48?h and C_max with the COPT but smaller T_max than the COPT and provided a more stable therapeutic concentration compared to the COPT. In conclusion, hydrophilic matrix tablet combining only different Mw PEOs as matrix materials had very good potential to be developed into a controlled-release drug delivery system for highly water-soluble drug. Besides, its manufacturing processes were succinct which would be preferable for modern medicine industry.     

In vitro and in vivo evaluation of folate-mediated PEGylated nanostructured lipid carriers for the efficient delivery of furanodiene

Furanodiene (FN) loaded FA-PEG₂₀₀₀-DSPE modified nanostructured lipid carriers (FA-FN-NLCs) were developed to increase the solubility and bioavailability of FN, prolong the circulation time in blood and improve the targeting ability. FA-FN-NLCs were prepared using emulsification-ultrasonic and low temperature-solidification method and optimized by central composition design (CCD). In vitro and in vivo characteristics of FA-FN-NLCs were investigated in detail. The optimized formulations exhibited a spherical shape with particle size of 127.4?±?2.62?nm, PDI of 0.268?±?0.04, zeta potential of –14.7?±?1.08?mV, high encapsulation efficiency of 89.04?±?2.26% and loading capacity of 8.46?±?0.20%. Differential scanning calorimetry (DSC) indicated that FN was not in crystalline state in FA-FN-NLCs. In vitro drug release exhibited a biphasic release pattern which showed a relative burst drug release at the initial time and followed by a prolonged drug release. In vivo, compared with FN solution (FN-SOL) and FN loaded traditional NLCs (FN-NLCs), FA-FN-NLCs had a longer blood circulating time (t_1/2) and higher area under the curve (AUC). NiR fluorescence imaging study demonstrated that FA-FN-NLCs specially accumulated in tumor site by the receptor-mediated endocytosis. This study showed that FA-FN-NLCs was a promising drug delivery system for FN in the treatment of cancer.     

Distribution of Melaleuca alternifolia essential oil in liposomes with Tween 80 addition and enhancement of in vitro antimicrobial effect

Tea tree oil (TTO) exhibits excellent broad-spectrum antimicrobial activity. In order to preserve it from the degradation in the presence of oxygen, light and temperature, TTO was encapsulated in liposomes (LTTOs) using the thin-membrane hydration and sonication method, and characterised by Zetasizer for size and size distribution, transmission electron microscope for morphology, zeta-potential for surface charge, entrapment efficiency and TTO release from the nanoparticles. The antimicrobial activities of phosphate-buffered saline solution containing TTO, unloaded liposomes and LTTOs suspension were determined by twofold serial broth dilution technique. The size of LTTOs was 75 nm and the encapsulation efficiency of 96.08% was obtained. LTTOs exhibited slow release of TTO and superior broad-spectrum antimicrobial effects compared with free TTO. Liposomes not only effectively encapsulated TTO to form a stable liposome suspension, but also enhanced inhibition and bactericidal effect on the TTO-tolerant strain. The liposomal systems carrying TTO may be a potential alternative for effective antimicrobial agents.     

Design and optimization of gastric floating sustained-release mini-tablets of alfuzosin hydrochloride based on a factorial design: in vitro/in vivo evaluation

Abstract

The purpose of this research was to develop multiple-unit gastric floating mini-tablets and to evaluate the possibility of using these mini-tablets as a delivery system to improve the drug absorption for drugs with a narrow absorption window. Mini-tablets were prepared using hydroxypropyl methylcellulose (HPMC K100M) and carbopol 971P as release retarding agents and sodium bicarbonate (NaHCO₃) as gas-forming agent. The properties of the prepared mini-tablets in terms of floating characteristic parameters and in vitro release were evaluated. Furthermore, in vivo gastric retention study in rats and in vivo pharmacokinetic study in rabbits of the optimized formulation were performed. The optimized mini-tablets containing 45% HPMC K100M, 15% stearyl alcohol, 13% carbopol 971P, and 12% NaHCO₃ were found to float immediately within 1?min and duration more than 9?h. The in vivo gastric retention study results indicated that the mini-tablets could retain in the stomach for more than 6.67?h. Furthermore, the AUC_0?t of the floating mini-tablets (6849.83?±?753.80?h ng·mL^?1) was significantly higher than that of marketed sustained-release tablets XATRAL®XL (4970.16?±?924.60?h ng·mL^?1). All these results illustrated that the gastric floating mini-tablets might be a promising drug delivery system for drugs with a narrow absorption window.     

Lonidamine solid dispersions: in vitro and in vivo evaluation

Solid dispersions of lonidamine in PEG 4000 and PVP K 29/32 were prepared by the spray-drying method. Then, the binary systems were studied and characterized using differential scanning calorimetry, hot stage microscopy, and x-ray diffractometry. In vitro dissolution studies of the solid dispersed powders were performed to verify if any lonidamine dissolution rate or water solubility improvement occurred. In vivo tests were carried out on the solid dispersions and on the cyclodextrin inclusion complexes to verify if this lonidamine water solubility increase was really able to improve the in vivo drug plasma levels. Drug water solubility was increased by the solid dispersion formation, and the extent of increase depended on the polymer content of the powder. The greater increase of solubility corresponded to the highest content of polymer. Both the solid dispersions and the cyclodextrin complexes were able to improve the in vivo bioavailability of the lonidamine when administered per os. Particularly, the AUC of the drug plasma levels was increased from 1.5 to 1.9-fold depending on the type of carrier.     

Preparation and in vitro/in vivo evaluation of azilsartan osmotic pump tablets based on the preformulation investigation

The objective of this study was to design and evaluate azilsartan osmotic pump tablets. Preformulation properties of azilsartan were investigated for formulation design. Azilsartan osmotic pump tablets were prepared by incorporation of drug in the core and subsequent coating with cellulose acetate and polyethylene glycol 4000 as semi-permeable membrane, then drilled an orifice at the center of one side. The influence of different cores, compositions of semipermeable membrane and orifice diameter on azilsartan release were evaluated. The formulation of core tablet was optimized by orthogonal design and the release profiles of various formulations were evaluated by similarity factor (f₂). The optimal formulation achieved to deliver azilsartan at an approximate zero-order up to 14?h. The pharmacokinetic study was performed in beagle dogs. The azilsartan osmotic pump tablets exhibited less fluctuation in blood concentration and higher bioavailability compared to immediate-release tablets. Moreover, there was a good correlation between the in vitro dissolution and in vivo absorption of the tablets. In summary, azilsartan osmotic pump tablets presented controlled release in vitro, high bioavailability in vivo and a good in vitro-in vivo correlation.     

Using acoustic cavitation to enhance chemotherapy of DOX liposomes: experiment in vitro and in vivo

Experiments in vitro and in vivo were designed to investigate tumor growth inhibition of chemotherapeutics-loaded liposomes enhanced by acoustic cavitation. Doxorubicin-loaded liposomes (DOX liposomes) were used in experiments to investigate acoustic cavitation mediated effects on cell viability and chemotherapeutic function. The influence of lingering sensitive period after acoustic cavitation on tumor inhibition was also investigated. Animal experiment was carried out to verify the practicability of this technique in vivo. From experiment results, blank phospholipid-based microbubbles (PBM) combined with ultrasound (US) at intensity below 0.3 W/cm(2) could produce acoustic cavitation which maintained cell viability at high level. Compared with DOX solution, DOX liposomes combined with acoustic cavitation exerted effective tumor inhibition in vitro and in vivo. The lingering sensitive period after acoustic cavitation could also enhance the susceptibility of tumor to chemotherapeutic drugs. DOX liposomes could also exert certain tumor inhibition under preliminary acoustic cavitation. Acoustic cavitation could enhance the absorption efficiency of DOX liposomes, which could be used to reduce DOX adverse effect on normal organs in clinical chemotherapy.     

Celecoxib-cyclodextrin systems: characterization and evaluation of in vitro and in vivo advantage

Solid dispersions of Celecoxib were prepared with hydroxypropyl β cyclodextrin by various methods such as physical mixture, cogrinding, kneading, and coevaporation. The dispersions were characterized by differential scanning calorimetry (DSC), X-ray diffraction patterns, infrared spectroscopy, and nuclear magnetic resonance studies. The DSC thermograms of the dispersions indicated potential of heat-induced interaction between Celecoxib and cyclodextrin that could influence in vitro drug dissolution. The dispersions exhibited faster rates of dissolution compared to that of Celecoxib. The kneaded dispersion with the fastest in vitro dissolution rate when compressed into tablets showed a better release profile compared to the tablets of pure Celecoxib. In vivo studies revealed that the kneaded dispersion provided for quicker response and was more effective in inhibiting rat paw edema as compared to Celecoxib alone, thus confirming the advantage of improved pharmacological activity of Celecoxib when administered as a solid dispersion with cyclodextrin.     

Solid lipid nanoparticles of anticancer drug andrographolide: formulation,in vitro and in vivo studies

Diterpenoidal anti-cancer drug andrographolide (AD) was encapsulated into solid lipid nanoparticle (SLN) because of poor aqueous solubility and high lipophilicity. AD-SLNs were prepared by solvent injection method and characterized for droplet size, surface morphology, zeta potential, etc. In vitro drug release was carried out by dialysis-membrane method. A pharmacokinetic study was performed by UPLC/Q-TOF-MS method to determine the maximum plasma concentration (C_max), area under the curve (AUC), etc. There was an improvement in C_max and AUC of AD-SLNs when compared with AD, thereby enhancing the bioavailability of AD. The t_max was increased than that of AD suspension, indicating the sustained release pattern of AD-SLNs. The antitumor activity was carried out on Balb/c mice showing better results with AD-SLNs as compared to AD. Thus, the AD-loaded SLNs would be useful for delivering poorly water-soluble AD with enhanced bioavailability and improved antitumor activity.