Enhanced Codelivery of Gefitinib and Azacitidine for Treatment of Metastatic-Resistant Lung Cancer Using Biodegradable Lipid Nanoparticles.

Lung cancer is a formidable challenge in clinical practice owing to its metastatic nature and resistance to conventional treatments. The codelivery of anticancer agents offers a potential solution to overcome resistance and minimize systemic toxicity. The encapsulation of these agents within nanostructured lipid carriers (NLCs) provides a promising strategy to enhance lymphatic delivery and reduce the risk of relapse. This study aimed to develop an NLC formulation loaded with Gefitinib and Azacitidine (GEF-AZT-NLC) for the treatment of metastatic-resistant lung cancer. The physicochemical properties of the formulations were characterized, and in vitro drug release was evaluated using the dialysis bag method. The cytotoxic activity of the GEF-AZT-NLC formulations was assessed on a lung cancer cell line, and hemocompatibility was evaluated using suspended red blood cells. The prepared formulations exhibited nanoscale size (235-272 nm) and negative zeta potential values (-15 to -31 mV). In vitro study revealed that the GEF-AZT-NLC formulation retained more than 20% and 60% of GEF and AZT, respectively, at the end of the experiment. Hemocompatibility study demonstrated the safety of the formulation for therapeutic use, while cytotoxicity studies suggested that the encapsulation of both anticancer agents within NLCs could be advantageous in treating resistant cancer cells. In conclusion, the GEF-AZT-NLC formulation developed in this study holds promise as a potential therapeutic tool for treating metastatic-resistant lung cancer.

Combined Ramipril and Black Seed Oil Dosage Forms Using Bioactive Self-Nanoemulsifying Drug Delivery Systems (BIO-SNEDDSs).

Purpose: Ramipril (RMP)­an angiotensin-converting enzyme (ACE) inhibitor­and thymoquinone (THQ) suffer from poor oral bioavailability. Developing a combined liquid SNEDDS that comprises RMP and black seed oil (as a natural source of THQ) could lead to several formulations and therapeutic benefits. Methods: The present study involved comprehensive optimization of RMP/THQ liquid SNEDDS using self-emulsification assessment, equilibrium solubility studies, droplet size analysis, and experimentally designed phase diagrams. In addition, the optimized RMP/THQ SNEDDS was evaluated against pure RMP, pure THQ, and the combined pure RMP + RMP-free SNEDDS (capsule-in-capsule) dosage form via in vitro dissolution studies. Results: The phase diagram study revealed that black seed oil (BSO) showed enhanced self-emulsification efficiency with the cosolvent (Transcutol P) and hydrogenated castor oil. The phase diagram studies also revealed that the optimized formulation BSO/TCP/HCO-30 (32.25/27.75/40 % w/w) showed high apparent solubility of RMP (25.5 mg/g), good THQ content (2.7 mg/g), and nanometric (51 nm) droplet size. The in-vitro dissolution studies revealed that the optimized drug-loaded SNEDDS showed good release of RMP and THQ (up to 86% and 89%, respectively). Similarly, the isolation between RMP and SNEDDS (pure RMP + RMP-free SNEDDS) using capsule-in-capsule technology showed >84% RMP release and >82% THQ release. Conclusions: The combined pure RMP + RMP-free SNEDDS (containing black seed oil) could be a potential dosage form combining the solubilization benefits of SNEDDSs, enhancing the release of RMP/THQ along with enhancing RMP stability through its isolation from lipid-based excipients during storage.

Nicotine and cotinine quantification after a 4-week inhalation of electronic cigarette vapors in male and female mice using UPLC-MS/MS.

OBJECTIVES: To detect the cotinine and nicotine serum concentrations of female and male C57BL/6J mice after a 4-week exposure to electronic (e)-cigarette vapors using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). METHODS: This experimental study was carried out at an animal facility and laboratories, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, between January and August 2020. A 4-week exposure to e-cigarettes was carried out using male and female mice and serum samples were obtained for cotinine and nicotine quantification using UPLC-MS/MS. The chromatographic procedures involved the use of a BEH HSS T3 C18 column (100 mm x 2.1 mm, 1.7 µm) with acetonitrile as a mobile phase and 0.1% formic acid (2:98 v/v). RESULTS: The applied methodology has highly efficient properties of detection, estimation, and extraction, where the limit of quantification (LOQ) for nicotine was 0.57 ng/mL and limit of detection (LOD) for nicotine was 0.19 ng/mL, while the LOQ for cotinine was 1.11 ng/mL and LOD for cotinine was 0.38 ng/mL. The correlation coefficient was r2>0.99 for both compounds. The average recovery rate was 101.6±1.33 for nicotine and 100.4±0.54 for cotinine, while the precision and accuracy for cotinine and nicotine were less than 6.1. The serum cotinine level was higher in males (433.7±19.55) than females (362.3±16.27). CONCLUSION: This study showed that the gender factor might play a crucial role in nicotine metabolism.

Formulation of Gelucire®-Based Solid Dispersions of Atorvastatin Calcium: In Vitro Dissolution and In Vivo Bioavailability Study.

Atorvastatin (ATV) is a poorly water-soluble drug that exhibits poor oral bioavailability. Therefore, present research was designed to develop ATV solid dispersions (SDs) to enhance the solubility, drug release, and oral bioavailability. Various SDs of ATV were formulated by conventional and microwave-induced melting methods using Gelucire®48/16 as a carrier. The formulated SDs were characterized for different physicochemical characterizations, drug release, and oral bioavailability studies. The results obtained from the different physicochemical characterization indicate the molecular dispersion of ATV within various SDs. The drug polymer interaction results showed no interaction between ATV and used carrier. There was marked enhancement in the solubility (1.95-9.32 folds) was observed for ATV in prepared SDs as compare to pure ATV. The drug content was found to be in the range of 96.19% ± 2.14% to 98.34% ± 1.32%. The drug release results revealed significant enhancement in ATV release from prepared SDs compared to the pure drug and the marketed tablets. The formulation F8 showed high dissolution performance (% DE30 value of 80.65 ± 3.05) among the other formulations. Optimized Gelucire®48/16-based SDs formulation suggested improved oral absorption of atorvastatin as evidenced with improved pharmacokinetic parameters (Cmax 2864.33 ± 573.86 ng/ml; AUC0-t 5594.95 ± 623.3 ng/h ml) as compared to ATV suspension (Cmax 317.82 ± 63.56 ng/ml; AUC0-t 573.94 ± 398.9 ng/h ml) and marketed tablets (Cmax 852.72 ± 42.63 ng/ml; 4837.4 ± 174.7 ng/h ml). Conclusively, solid dispersion-based oral formulation of atorvastatin could be a promising approach for enhanced drug solubilization, dissolution, and subsequently improved absorption.

Solubilization and thermodynamic properties of simvastatin in various micellar solutions of different non-ionic surfactants: Computational modeling and solubilization capacity.

The aim of this work was to solubilize simvastatin (SIM) using different micellar solutions of various non-ionic surfactants such as Tween-80 (T80), Tween-20 (T20), Myrj-52 (M52), Myrj-59 (M59), Brij-35 (B35) and Brij-58 (B58). The solubility of SIM in water (H2O) and different micellar concentrations of T80, T20, M52, M59, B35 and B58 was determined at temperatures T = 300.2 K to 320.2 K under atmospheric pressure p = 0.1 MPa using saturation shake flask method. The experimental solubility data of SIM was regressed using van't Hoff and Apelblat models. The solubility of SIM (mole fraction) was recorded highest in M59 (1.54 x 10-2) followed by M52 (6.56 x 10-3), B58 (5.52 x 10-3), B35 (3.97 x 10-3), T80 (1.68 x 10-3), T20 (1.16 x 10-3) [the concentration of surfactants was 20 mM in H2O in all cases] and H2O (1.94 x 10-6) at T = 320.2 K. The same results were also recorded at each temperature and each micellar concentration of T80, T20, M52, M59, B35 and B58. "Apparent thermodynamic analysis" showed endothermic and entropy-driven dissolution/solubilization of SIM in H2O and various micellar solutions of T80, T20, M52, M59, B35 and B58.

Crosstalk of low density lipoprotein and liposome as a paradigm for targeting of 5-fluorouracil into hepatic cells: cytotoxicity and liver deposition.

This study aimed to utilize cholesterol conjugation of 5-fluorouracil (5-FUC) and liposomal formulas to enhance the partitioning of 5-FU into low density lipoprotein (LDL) to target hepatocellular carcinoma (HCC). Thus, 5-FU and 5-FUCwere loaded into liposomes. Later, the direct loading and transfer of 5-FU, and 5-FUC from liposomes into LDL were attained. The preparations were characterized in terms of particle size, zeta potential, morphology, entrapment efficiency, and cytotoxicity using the HepG2 cell line. Moreover, the drug deposition into the LDL and liver tissues was investigated. The present results revealed that liposomal preparations have a nanosize range (155 - 194 nm), negative zeta potential (- 0.82 to - 16 mV), entrapment efficiency of 69% for 5-FU, and 66% for 5-FUC. Moreover, LDL particles have a nanosize range (28-49 nm), negative zeta potential (- 17 to -27 mV), and the entrapment efficiency is 11% for 5-FU and 85% for 5-FUC. Furthermore, 5-FUC loaded liposomes displayed a sustained release profile (57%) at 24 h compared to fast release (92%) of 5-FU loaded liposomes. 5-FUC and liposomal formulas enhanced the transfer of 5-FUC into LDL compared to 5-FU. 5-FUC loaded liposomes and LDL have greater cytotoxicity against HepG2 cell lines compared to 5-FU and 5-FUC solutions. Moreover, the deposition of 5-FUC in LDL (26.87ng/mg) and liver tissues (534 ng/gm tissue) was significantly increased 5-FUC liposomes compared to 5-FU (11.7 ng/g tissue) liposomal formulation. In conclusion, 5-FUC is a promising strategy for hepatic targeting of 5-FU through LDL-mediated gateway.

Enhancing Oral Bioavailability of Apigenin Using a Bioactive Self-Nanoemulsifying Drug Delivery System (Bio-SNEDDS): In Vitro, In Vivo and Stability Evaluations.

Apigenin (APG) is a very well-known flavonoid for its anti-inflammatory and anticancer properties. The purpose of this study is to improve the solubility and bioavailability of APG using a stable bioactive self-nanoemulsifying drug delivery system (Bio-SNEDDS). APG was incorporated in an oil phase comprising coconut oil fatty acid, Imwitor 988, Transcutol P, and HCO30 to form a Bio-SNEDDS. This preparation was characterized for morphology, particle size, and transmission electron microscopy (TEM). The APG performance was investigated in terms of loading, precipitation, release and stability tests from the optimal Bio-SNEDDS. An antimicrobial test was performed to investigate the activity of the Bio-SNEDDS against the selected strains. Bioavailability of the Bio-SNEDDS was evaluated using Wister rats against the commercial oral product and the pure drug. The results demonstrated the formation of an efficient nanosized (57 nm) Bio-SNEDDS with a drug loading of 12.50 mg/gm which is around 500-fold higher than free APG. TEM analysis revealed the formation of spherical and homogeneous nanodroplets of less than 60 nm. The dissolution rate was faster than the commercial product and was able to maintain 90% APG in gastro intestinal solution for more than 4 h. A stability study demonstrated that the Bio-SNEDDS is stable at a harsh condition. The in vivo pharmacokinetics parameters of the Bio-SNEDDS formulation in comparison to the pure drug showed a significant increase in maximum concentration (Cmax) and area under the curve (AUC (0-t)) of 105.05% and 91.32%, respectively. Moreover, the antimicrobial study revealed moderate inhibition in the bacterial growth rate. The APG-Bio-SNEDDS could serve as potential carrier aimed at improving the clinical application of APG.

Enhanced Dissolution of Luteolin by Solid Dispersion Prepared by Different Methods: Physicochemical Characterization and Antioxidant Activity.

Luteolin (LT) is a poorly soluble bioactive compound that suffered bioavailability problems after oral administration. Hence, the aim of the proposed research work was to formulate and investigate various solid dispersions (SDs) of LT in order to enhance its dissolution and bioactivity. LT-SD was prepared using polyethylene glycol 4000 (PEG 4000) as a carrier at the mass ratios of 1:1, 1:2, and 1:4. LT-SD was prepared using different methods including fusion (FU), solvent evaporation (SE), and microwave irradiation (MI) methods. The prepared LT-SD was duly characterized in terms of differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), infrared (IR) spectroscopy, and nuclear magnetic resonance (NMR) and evaluated for dissolution and in vitro antioxidant activity. The results of DSC, XRD, SEM, IR, and NMR suggested the formation of LT-SD. After 90 min of the dissolution study, the results displayed that the % release of LT from prepared SD was significantly higher compared with the pure LT and its physical mixture dispersion (PMD). LT-SD prepared using the MI method displayed the maximum release of LT (i.e., 97.78 ± 4.41%) at a 1:2 mass ratio of LT:PEG 4000. The LT-SD prepared using the SE method displayed the maximum release of 93.78 ± 3.98% at a mass ratio of 1:4 of LT:PEG 4000. The SD prepared by the MI method showed enhanced dissolution due to higher aqueous solubility and the reduction of particle size. The solid-state characterization studies (DSC, XRD, SEM, IR, and NMR studies) suggested the morphological conversion of LT into the amorphous form from the crystalline state. The results of the antioxidant study revealed that the formation LT-SD displayed significantly higher radical scavenging activity than the pure LT. Therefore, SD obtained using PEG 4000 could be a potential strategy for maximizing the solubility, in vitro dissolution, and therapeutic efficacy of LT.

Rat palatability, pharmacodynamics effect and bioavailability of mefenamic acid formulations utilizing hot-melt extrusion technology.

Mefenamic acid (MA) has been reported as a weakly soluble drug which presents weak in vivo absorption upon oral administration using conventional formulations. Solid dispersions (SDs) have been investigated extensively in literature for enhancing the solubility and bioavailability of weakly-soluble molecules. Hence, the aim of proposed study was to prepare MA novel formulations in the form of SDs using hot-melt extrusion technology in order to enhance its palatability, bioavailability, and pharmacodynamics effects/anti-inflammatory efficacy. Various SDs of MA were prepared using hot-melt extrusion technology, characterized physically and investigated for dissolution tests. Optimized SD formulations of MA were being subjected to palatability, pharmacodynamics, and pharmacokinetic studies in rats. Optimized SD of MA showed significant rat palatability tastes as compared with pure and marketed MA (p < .05). Anti-inflammatory efficacy of 20% SD and 25% SD of MA was found to be 86.44 and 89.83%, respectively, in comparison with 74.57 and 78.24% by pure MA and marketed MA, respectively. The anti-inflammatory efficacy of optimized SD was found to be significant as compared with pure and marketed MA (p < .05). The oral absorption of MA from optimized 20% SD was also noted as statistically significant as compared with pure MA (p < .05). The relative bioavailability of MA from 20 and 25% SDs was 2.97 and 2.24-folds higher than pure MA. The results of this study suggested that SDs prepared using hot-melt extrusion technology are capable to enhance palatability, anti-inflammatory efficacy, and oral bioavailability of MA in comparison with pure drug.

Defining the process parameters affecting the fabrication of rosuvastatin calcium nanoparticles by planetary ball mill.

PURPOSE: Rosuvastatin calcium (ROSCa) nanoparticles were fabricated by planetary ball mill to enhance ROSCa dissolution rate and bioavailability. METHODS: Milling time factors (milling cycle time and number as well as pause time) were explored. The effect of different milling ball size, speed, and solid-to-solvent ratio were also studied using Box-Behnken factorial design. The fabricated nanoparticles were evaluated in term of physicochemical properties and long-term stability. RESULTS: The obtained data revealed that the integrated formulation and process factors should be monitored to obtain desirable nanoparticle attributes in terms of particle size, zeta potential, dissolution rate, and bioavailability. The optimized ROSCa nanoparticles prepared by milling technique showed a significant enhancement in the dissolution rate by 1.3-fold and the plasma concentration increased by 2-fold (P<0.05). Moreover, stability study showed that the optimized formula of ROSCa nanoparticles exhibits higher stability in long-term stability conditions at 30°C with humidity of 60%. CONCLUSION: Formulation of ROSCa as nanoparticles using milling technique showed a significant enhancement in both dissolution rate and plasma concentration as well as stability compared with untreated drug.

Evaluation of the bioavailability of hydrocortisone when prepared as solid dispersion.

This study was conducted to formulate, characterize, and investigate the bioavailability of hydrocortisone (HCT) when prepared as solid dispersions. HCT was mixed in an organic solvent with polyethylene glycol 4000 (PEG 4000) and Kolliphor® P 407. Spray drying technique was employed to form a solid dispersion formulation at a specific ratio. Physical and chemical characterization of the formed particles were achieved using differential scanning calorimetry, scanning electron microscopy, Fourier transform infrared spectroscopy, and powder X-ray diffractometry. Furthermore, comparative in vitro and in vivo studies were conducted between the formulated particles against neat HCT. The formulated solid dispersion showed elongated particles with leaf-like structure. Formation of new chemical bonds in the formed particle was suggested due to the change in the vibrational wave numbers and the significant improvement in the bioavailability of the dispersed particles proved the importance of this technique.

UHPLC assisted simultaneous separation of apigenin and prednisolone and its application in the pharmacokinetics of apigenin.

A new ultra-high performance liquid chromatography-mass spectrometry-mass spectrometry (UHPLC-MS/MS) system has been formulated for the resolution of closely related drugs apigenin (API, a bioflavinoid) and prednisolone (PRD) from their mixture. This developed method comprised of a "BEH™ C18 column (50 mm × 2.1 mm, 1.7 µm)" using acetonitrile and 0.1% formic acid (35:65 v/v) at a supply rate of 0.25 mL·min-1 as eluent. It was found that selected eluent provided short run time (≤2.5 min) as well as better peak symmetry. Satisfactory values of chromatographic parameters such as resolution (Rs = 2.5), capacity factor (k; 13.6 and 23.4 for API and PRD respectively, selectivity (α = 1.72) and number of theoretical plates (N; 3789 and 42,435 for API and PRD respectively) indicate the efficiency of the developed method. The obtained separation was then exploited for the detection and measurement of API in rat plasma sample by means of PRD as an "internal standard" (IS). The eluted compounds in plasma were identified by tandem mass spectrometry by means of tandem quadrupole (TQ) detector ("Waters Corp., Milford, MA") fortified with an "electrospray ionisation (ESI)" source functioning in positive ionization mode. The determination of API in plasma was accomplished by means of "multiple reactions monitoring (MRM)" mode. Assortment of "ionization pairs" (m/z) was displayed in the following manner: API: 270.99 → 152.9 ("cone voltage" 57 V, "collision energy" 34 V), PRD: 403.172 → 385.224 ("cone voltage" 42 V, "collision energy" 13 V). The calibration curves followed linearity in concentration range of 05-1000 ng mL-1 with limit of detection "LOD" and limit of quantification "LOQ" of 7.30 and 22.77 ng mL-1, respectively. The developed method was validated taking into consideration various test conditions and satisfactory values of various parameters such as linearity (r2 ±â€¯SD = 0.9995 ±â€¯0.0005), interday accuracy (88-120%), interday precision % RSD = 3.30-13.65% whereas intraday accuracy (91-118%) intraday precision % RSD = 1.18-5.83) indicated its validity. The validation outcomes fulfilled the standards of united states food and drug administration "USFDA" in addition Scientific Working Group for Forensic Toxicology "SWGTOX" guiding principles and were not beyond the tolerable constraint. The process developed in plasma was efficaciously harnessed in the pharmacokinetic investigation of various formulations of API after oral administration in rats.

Application of a quality-by-design approach for utilizing sodium stearyl fumarate as a taste-masking agent in dextromethorphan hydrobromide orally disintegrating tablets.

Orally dissolving tablets (ODTs) represent one of the recent advances in drug delivery. The foremost objective of this study was to optimize the utilization of lubricant sodium stearyl fumarate in the preparation of dextromethorphan hydrobromide ODTs with enhanced taste-masking properties. The simple blending of sodium stearyl fumarate with the powder bed would result in taste-masking through physical adsorption of the lubricant particles on the drug particles. A randomized 32 full factorial experimental design was used to characterize the relationship between lubricant ratio (X1), mixing time (X2), and the tablet properties. The tablets were assessed for friability, hardness, disintegration time, and in-vitro dissolution. All tablets showed hardness within the range of 3.0-3.7 kp, and the % loss in friability test was less than 1.1%. The in-vitro disintegration time ranged between 9 and 25 s. An in-vitro drug release study of the prepared ODTs showed that more than 90% of the drug was released within 30 min. A palatability test of the optimized formula conducted in human volunteers showed acceptable taste and mouthfeel with in-vivo disintegration time of 17 s. Thus, results obtained convincingly showed successful fast disintegration of the prepared tablets and acceptable palatability when using sodium stearyl fumarate as a taste masking agent.

Dissolution and bioavailability improvement of bioactive apigenin using solid dispersions prepared by different techniques.

Apigenin (APG) is a poorly soluble bioactive compound/nutraceutical which shows poor bioavailability upon oral administration. Hence, the objective of this research work was to develop APG solid dispersions (SDs) using different techniques with the expectation to obtain improvement in its in vitro dissolution rate and in vivo bioavailability upon oral administration. Different SDs of APG were prepared by microwave, melted and kneaded technology using pluronic-F127 (PL) as a carrier. Prepared SDs were characterized using "thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), Fourier transform infra-red (FTIR) spectrometer, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM)". After characterization, prepared SDs of APG were studied for in vitro drug release/dissolution profile and in vivo pharmacokinetic studies. The results of TGA, DSC, FTIR, PXRD and SEM indicated successful formation of APG SDs. In vitro dissolution experiments suggested significant release of APG from all SDs (67.39-84.13%) in comparison with control (32.74%). Optimized SD of APG from each technology was subjected to in vivo pharmacokinetic study in rats. The results indicated significant improvement in oral absorption of APG from SD prepared using microwave and melted technology in comparison with pure drug and commercial capsule. The enhancement in oral bioavailability of APG from microwave SD (319.19%) was 3.19 fold as compared with marketed capsule (100.00%). Significant enhancement in the dissolution rate and oral absorption of APG from SD suggested that developed SD systems can be successfully used for oral drug delivery system of APG.

Female radical cystectomy patients have a higher risk of surgical site infections.

INTRODUCTION: Surgical site infections (SSI) are common after radical cystectomy. The objectives of this study were to evaluate if female sex is associated with postoperative SSI and if experiencing an SSI was associated with subsequent adverse events. METHODS: This was a historical cohort study of radical cystectomy patients from the American College of Surgeons' National Surgical Quality Improvement Program database between 2006 and 2016. The primary outcome was development of a SSI (superficial, deep, or organ/abdominal space) within 30 days of surgery. Multivariable logistic regression analyses were performed to determine the association between sex and other patient/procedural factors with SSI. Female patients with SSI were also compared to those without SSI to determine risk of subsequent adverse events. RESULTS: A total of 9,275 radical cystectomy patients met the inclusion criteria. SSI occurred in 1,277(13.7%) patients, 308 (16.4%) females and 969 (13.1%) males (odds ratio = 1.27; 95% confidence interval 1.10-1.47; P = 0.009). Infections were superficial in 150 (8.0%) females versus 410 (5.5%) males (P < 0.0001), deep in 40 (2.1%) females versus 114 (1.5%) males (P = 0.07), and organ/abdominal space in 118 (6.2%) females versus 445 (6.0%) males (P = 0.66). On multivariable analysis, female sex was independently associated with SSI (odds ratio = 1.21 confidence interval 1.01-1.43 P = 0.03). Females who experience SSI had higher probability of developing other complications including wound dehiscence, septic shock, and need for reoperation (all P < 0.05). CONCLUSIONS: Female sex is an independent risk factor for SSI following radical cystectomy. More detailed study of patient factors, pathogenic microbes, and treatment factors are needed to prescribe the best measures for infection prophylaxis.

Evaluation of wound healing activity of henna, pomegranate and myrrh herbal ointment blend.

This study assessed the wound healing potential and antimicrobial activity of henna, pomegranate and myrrh extract formulations and their blend in excision, and dead space wound models in rats in comparison to a marketed ointment (gentamycin). The natural extracts were used in ointment formulations alone or in a combination of three extracts at a total concentration of 15% w/w in medications. The percent of wound contraction in case of henna, myrrh, pomegranate, the blend and gentamycin (10 mg/kg) were 85.90-98.5%, 88.35-99.52%, 93.55-100%, 97.30-100%, and 90.25-100% from days 16 to 20, respectively. The blended formulation showed the highest increase in the percent of wound contraction and decrease in the epithelisation period compared to other formulations and showed comparable results to the standard ointment. The histological studies of excision biopsy at day 24 showed healed skin structures with normal epithelisation, the restoration of adnexa and fibrosis within the dermis in all of the formulation- and gentamycin-treated groups while the control group lagged behind in the formation of the amount of ground substance in the granulation tissue. The formulations showed antimicrobial activity against Candida, Staphylococcus aureus, mucous membrane infections and E. coli topical infections. The study proved the wound healing potential and antimicrobial activity of the herbal extract.

Rosuvastatin calcium nanoparticles: Improving bioavailability by formulation and stabilization codesign.

PURPOSE: Rosuvastatin calcium (ROSCa) is a poorly soluble drug with bioavailability not exceeding 20%. Decreasing the particle size may enhance its solubility, dissolution rate and bioavailability. Therefore, the aim of the current study is to prepare ROSCa nanoparticles by wet milling technique using planetary ball mill. The codesign between formulation and stabilization of nanoparticles was studied to achieve both high dissolution as well as bioavailability. METHODOLOGY: ROSCa nanosuspensions was prepared by wet milling technique using planetary ball mill, by applying milling ball size of 0.1 mm at speed of 800 rpm for 3 cycles each cycle composed of 10 minutes. HPMC, PVP k-30, pluronic F-127, Tween 80 and PEG 6000 were used as stabilizers. The nanosuspensions were then freeze-dried, and the dried nanoparticles were evaluated for particle size, zeta potential, in-vitro dissolution test, XRPD and in-vivo study. RESULTS: ROSCa nanoparticles stabilized with 10% PVP (P3) had a good stability with smallest particle size, which in turn enhanced the dissolution rate. The particle size of the leading formula was 461.8 ± 16.68 nm with zeta potential of -31.8 ± 7.22 mV compared to untreated drug that has a particle size of 618µm. The percent of ROSCa dissolved after 1 hour enhanced significantly which reached 72% and 58.25% for leading nanoparticle formula and untreated ROSCa, respectively (P < 0.05). The in-vivo study of ROSCa from the leading nanoparticle formula showed a significant enhancement in the Cmax after 2 h (82.35 ng/ml) compared to 9.2 ng/ml for untreated drug. CONCLUSION: Wet milling technique is a successful method to prepare ROSCa nanoparticles. From different stabilizer used, PVP (10%) was able to produce stable nanoparticle with small particle size which significantly enhance the dissolution rate and pharmacokinetics parameters of ROSCa.

Long-term patient outcomes from the first year of a robotic surgery program using multi-surgeon implementation.

INTRODUCTION: There is concern that surgical quality initially declines during the learning phase of robotic surgery. At our institution, we used a multi-surgeon programmatic approach to the introduction of robotic surgery. The purpose of this study was to evaluate outcomes of patients treated during the first year of our program. METHODS: This is a historical cohort of all radical prostatectomy patients during a one-year period. Baseline, perioperative, and long-term followup data were prospectively and retrospectively collected. Treatment failure was a composite of any postoperative radiation, androgen-deprivation, or prostate-specific antigen (PSA) ≥0.2. RESULTS: During the study period, 225 radical prostatectomy procedures were performed (104 robotic and 121 open). Baseline characteristics were similar between groups (p>0.05). All patients were continent and 74% were potent prior to surgery. Mean estimated blood loss (280 cc vs. 760 cc; p<0.001) and blood transfusion (0% vs. 8.3%; p=0.002) was lower in the robotic cohort. Non-transfusion complications were similar between groups (13% vs. 12%; p=0.7). Mean hospital stay was shorter in the robotic cohort (1.4 vs. 2.5 days). There was no difference in overall positive margin rate (38% vs. 43%; p=0.4) or treatment failure at a median followup of 3.5 years (p=0.4). Robotically treated patients were more often continent (89% vs. 77%; p=0.02) and potent (48% vs. 32%; p=0.02). CONCLUSIONS: Using an inclusive multi-surgeon approach, robotic pros-tatectomy was introduced safely at a Canadian academic institution.