Effect of a Novel Sugar Blend on Weight and Cardiometabolic Health among Healthy Indian Adults: A Randomized, Open-Label Study.

Obesity is one of the major factors contributing to noncommunicable diseases (NCDs), which is associated with a high intake of a sugar-rich diet. Sugar blend (a novel combination of sugar and stevia) has half the calories of sugar with the same sweetness at recommended use and offers better compliance. A randomized controlled trial was conducted to evaluate the efficacy and safety of this sugar blend in normal to mildly overweight subjects with a body mass index (BMI) of 23−26 kg/m. Sixty subjects were categorized into Group A: Sugar group (n = 30), and Group B: Sugar blend group (n = 30). The primary outcomes evaluated were weight, waist circumference, hip circumference, waist/hip ratio, BMI, and the secondary outcomes evaluated were lipid profile, random blood sugar, and HbA1c. All these parameters were assessed at baseline, 30 days, 60 days, and 90 days. Group B showed a significantly higher weight loss (p = 0.013) at 90 days compared with Group A. A significant reduction in waist circumference (p < 0.0001) by 4.4 cm was noted at 90 days, in addition to reduction in total cholesterol (p < 0.0001), triglyceride (p = 0.006), LDL cholesterol (p = 0.0490), and VLDL cholesterol (p = 0.006) in Group B compared with the baseline. The study revealed that the sugar blend is an effective formulation in reducing weight, anthropometric factors, and other related metabolic parameters. It has been proven to be well tolerated and promotes weight loss when used in conjunction with a daily balanced diet and exercise plan.

Nanotechnology-Based Celastrol Formulations and Their Therapeutic Applications.

Celastrol (also called tripterine) is a quinone methide triterpene isolated from the root extract of Tripterygium wilfordii (thunder god vine in traditional Chinese medicine). Over the past two decades, celastrol has gained wide attention as a potent anti-inflammatory, anti-autoimmune, anti-cancer, anti-oxidant, and neuroprotective agent. However, its clinical translation is very challenging due to its lower aqueous solubility, poor oral bioavailability, and high organ toxicity. To deal with these issues, various formulation strategies have been investigated to augment the overall celastrol efficacy in vivo by attempting to increase the bioavailability and/or reduce the toxicity. Among these, nanotechnology-based celastrol formulations are most widely explored by pharmaceutical scientists worldwide. Based on the survey of literature over the past 15 years, this mini-review is aimed at summarizing a multitude of celastrol nanoformulations that have been developed and tested for various therapeutic applications. In addition, the review highlights the unmet need in the clinical translation of celastrol nanoformulations and the path forward.

Oral Bioavailability Evaluation of Celastrol-Encapsulated Silk Fibroin Nanoparticles Using an Optimized LC-MS/MS Method.

Celastrol (CL), a compound isolated from Tripterygium wilfordii, possesses various bioactivities such as antitumor, anti-inflammatory and anti-obesity effects. In previous studies, we developed CL-encapsulated silk fibroin nanoparticles (CL-SFNP) with satisfactory formulation properties and in vitro cancer cytotoxicity effect. For further in vivo oral bioavailability evaluation, in this study, a simple and reliable LC-MS/MS method was optimized and validated to determine CL concentration in rat plasma. The separation of CL was performed on a C18 column (150 by 2 mm, 5 µm) following sample preparation using liquid-liquid extraction with the optimized extraction solvent of tert-butyl methylether. The assay exhibited a good linearity in the concentration range of 0.5-500 ng/mL with the lower limit of quantification (LLOQ) of 0.5 ng/mL. The method was validated to meet the requirements for bioassay with accuracy of 91.1-110.0%, precision (RSD%) less than 9.1%, extraction recovery of 63.5-74.7% and matrix effect of 87.3-101.2%. The developed method was successfully applied to the oral bioavailability evaluation of CL-SFNP. The pharmacokinetic results indicated the AUC0-∞ values of CL were both significantly (p < 0.05) higher than those for pure CL after intravenous (IV) or oral (PO) administration of equivalent CL in rats. The oral absolute bioavailability (F, %) of CL significantly (p < 0.05) increased from 3.14% for pure CL to 7.56% for CL-SFNP after dosage normalization. This study provides valuable information for future CL product development.

Cancer Chemoprevention Using Nanotechnology-Based Approaches.

Cancer research in pursuit of better diagnostic and treatment modalities has seen great advances in recent years. However, the incidence rate of cancer is still very high. Almost 40% of women and men are diagnosed with cancer during their lifetime. Such high incidence has not only resulted in high mortality but also severely compromised patient lifestyles, and added a great socioeconomic burden. In view of this, chemoprevention has gained wide attention as a method to reduce cancer incidence and its relapse after treatment. Among various stems of chemoprevention research, nanotechnology-based chemoprevention approaches have established their potential to offer better efficacy and safety. This review summarizes recent advances in nanotechnology-based chemoprevention strategies for various cancers with emphasis on lung and bronchial cancer, colorectal, pancreatic, and breast cancer and highlights the unmet needs in this developing field towards successful clinical translation.

Efficacy and Pharmacokinetic Considerations of Loratadine Nanoformulations and its Combinations for Pancreatic Cancer Chemoprevention.

PURPOSE: Pancreatic cancer (PC) is predicted to become the second leading cause of cancer associated deaths by 2020. Earlier, we confirmed the development and efficacy of our novel Loratadine Self-Microemulsifying-Drug-Delivery-System - Sulforaphane (LOR SMEDDS -SFN) nanoformulation in PC chemoprevention. In this report, we extend our studies to evaluate the PC chemoprevention efficacy of LOR SMEDDS - SFN. METHODS: The nanoformulation was subjected to in vitro colony formation assays, in vivo oral pharmacokinetics and stability studies. RESULTS: The colony formation assay using Panc-1 PC cells demonstrated a survival fraction of 0.74 with LOR-SFN (p < 0.001) which further reduced to 0.35 with LOR SMEDDS-SFN treatment (p < 0.0001) confirming the synergistic chemoprevention efficacy of the nanoformulation. Further, the oral pharmacokinetic studies of LOR SMEDDS-SFN showed 4-fold and 9-fold increase in Cmax (503.2 ± 5.8 ng/mL) and oral bioavailability (20,274.8 ± 3711.0 ng·h/mL) for LOR compared to LOR-SFN combination respectively assuring the enhanced performance by the SMEDDS. Additionally, the formulation exhibited statistically non-significant alteration in globule size, zeta potential, drug content and in vitro drug release during stability studies confirming its stability and pharmaceutical acceptability. CONCLUSION: Our studies have demonstrated a potential of LOR SMEDDS-SFN nanoformulation as an effective PC chemoprevention strategy.

Optimization of Preparation and Preclinical Pharmacokinetics of Celastrol-Encapsulated Silk Fibroin Nanoparticles in the Rat.

Celastrol (CL), a bioactive compound isolated from Tripterygium wilfordii, has demonstrated bioactivities against a variety of diseases including cancer and obesity. However, its poor water solubility and rapid in vivo clearance limit its clinical applications. To overcome these limitations, nanotechnology has been employed to improve its pharmacokinetic properties. Nanoparticles made of biological materials offer minimal adverse effects while maintaining the efficacy of encapsulated therapeutics. Silk fibroin (SF) solution was prepared successfully by extraction from the cocoons of silkworms, and a final concentration of 2 mg/mL SF solution was used for the preparation of CL-loaded SF nanoparticles (CL-SFNP) by the desolvation method. A stirring speed of 750 rpm and storage time of 20 h at -20 °C resulted in optimized product yield. A high-performance liquid chromatography (HPLC) method was developed and validated for the analysis of CL in rat plasma in terms of selectivity, linearity, intra-/inter-day precision and accuracy, and recovery. No interference was observed in rat plasma. Linearity in the concentration range of 0.05-5 µg/mL was observed with R2 of 0.999. Precision and accuracy values were below the limit of acceptance criteria, i.e., 15% for quality control (QC) samples and 20% for lower limit of quantification (LLOQ) samples. Rats were given intravenous (IV) administration of 1 mg/kg of pure CL in PEG 300 solution or CL-SFNP. The pharmacokinetic profile was improved with CL-SFNP compared to pure CL. Pure CL resulted in a maximum concentration (Cmax) value of 0.17 µg mL-1 at 5 min following administration, whereas that for CL-SFNP was 0.87 µg mL-1 and the extrapolated initial concentrations (C0) were 0.25 and 1.09 µg mL-1, respectively, for pure CL and CL-SFNP. A 2.4-fold increase in total area under the curve (AUC0-inf) (µg h mL-1) was observed with CL-SFNP when compared with pure CL. CL-SFNP demonstrated longer mean residence time (MRT; 0.67 h) than pure CL (0.26 h). In conclusion, the preparation of CL-SFNP was optimized and the formulation demonstrated improved pharmacokinetic properties compared to CL in solution following IV administration.

Pancreatic Cancer: Recent Advances in Nanoformulation-Based Therapies.

Pancreatic cancer is the fourth leading cause of death in the United States and has a 5-year life expectancy of ~8%. Currently, only a few drugs have been approved by the United States Food and Drug Administration for pancreatic cancer treatment. Despite available drug therapy and ongoing clinical investigations, the high prevalence and mortality associated with pancreatic cancer mean that there is an unmet chemopreventive and therapeutic need. From ongoing studies with various novel formulations, it is evident that the development of smart drug delivery systems will improve delivery of drug cargo to the pancreatic target site to ensure and enhance the therapeutic/chemoprevention efficacy of existing drugs and newly designed drugs in the future. With this in view, nanotechnology is emerging as a promising avenue to enhance drug delivery to the pancreas via both passive and active targeting mechanisms. Research in this field has grown extensively over the past decade, as is evident from available scientific literature. This review summarizes the recent advances that have brought nanotechnology-based formulations to the forefront of pancreatic cancer treatment.

Loratadine self-microemulsifying drug delivery systems (SMEDDS) in combination with sulforaphane for the synergistic chemoprevention of pancreatic cancer.

Pancreatic cancer (PC), currently the third leading cause of cancer-related deaths in the USA, is projected to become the second leading cause, behind lung cancer, by 2020. The increasing incidence, low survival rate, and limited treatment opportunities necessitate the use of alternative approaches such as chemoprevention, to tackle PC. In this study, we report significant synergistic chemoprevention efficacy for the first time from a low-dose combination of a classical antihistaminic drug, Loratadine (LOR) and a neutraceutical compound, Sulforaphane (SFN) using a self-microemulsifying drug delivery system (SMEDDS) formulation. The formulation was developed using Quality by Design approach (globule size, 95.13 ± 7.9 nm; PDI, 0.17 ± 0.04) and revealed significant (p < 0.05) enhancement in the in vitro dissolution profile confirming the enhanced solubility of BCS class II drug LOR with SMEDDS formulation. The LOR-SFN combination revealed ~ 40-fold reduction in IC50 concentration compared to LOR alone in MIA PaCa-2 and Panc-1 cell lines respectively, confirming the synergistic enhancement in chemoprevention. Further, the nanoformulation resulted in ~ 7-fold and ~ 11-fold reduction in IC50 values compared to LOR-SFN combination. Hence, our studies successfully demonstrate that a unique low-dose combination of LOR encapsulated within SMEDDs with SFN shows significantly enhanced chemopreventive efficacy of PC.

Pancreatic Cancer: Recent Advances in Nanoformulation-Based Therapies.

Pancreatic cancer is the fourth leading cause of death in the United States and has a 5-year life expectancy of ~8%. Currently, only a few drugs have been approved by the United States Food and Drug Administration for pancreatic cancer treatment. Despite available drug therapy and ongoing clinical investigations, the high prevalence and mortality associated with pancreatic cancer mean that there is an unmet chemopreventive and therapeutic need. From ongoing studies with various novel formulations, it is evident that the development of smart drug delivery systems will improve delivery of drug cargo to the pancreatic target site to ensure and enhance the therapeutic/chemoprevention efficacy of existing drugs and newly designed drugs in the future. With this in view, nanotechnology is emerging as a promising avenue to enhance drug delivery to the pancreas via both passive and active targeting mechanisms. Research in this field has grown extensively over the past decade, as is evident from available scientific literature. This review summarizes the recent advances that have brought nanotechnology-based formulations to the forefront of pancreatic cancer treatment.

Novel nano-drug combination therapeutic regimen demonstrates significant efficacy in the transgenic mouse model of pancreatic ductal adenocarcinoma.

The current work studied the chemopreventive efficacy of orally administered chitosan coated solid-lipid nanoparticle (c-SLN) encapsulated aspirin (ASP), curcumin (CUR) and free sulforaphane (SFN), ACS-cSLN, in the LSL-Kras G12D/+; Pdx-1 Cre/+ transgenic mouse model of pancreatic ductal adenocarcinoma (PDAC). In vitro uptake study and intracellular localization of ODA-FITC labeled ASP and CUR c-SLNs were performed in Panc-1 and MIA PaCa-2 cells by fluorescence microscopy. LSL-Kras G12D/+; Pdx-1 Cre/+ transgenic mice (n = 30) were randomly divided into 5 groups. Treatment groups were orally gavaged with ACS c-SLNs in three doses: low (2 + 4.5 + 0.16 mg/kg), medium (20 + 45 + 1.6 mg/kg) and high (60 + 135 + 4.8 mg/kg), respectively. After 20 weeks of treatment, mice pancreas were harvested, stained with dye and scored according to various pancreatic intraepithelial neoplasms (PanIN) categories by an independent observer. In vitro, cellular uptake evaluated on Panc-1 and MIA PaCa-2 cells resulted in higher fluorescence intensities, indicating increased cellular uptake of ASP and CUR c-SLNs. For further evidence, the addition of lysoID (red fluorescence) demonstrated location and uptake of ASP and CUR c-SLNs into the lysosome. In vivo, treatment with ACS c-SLN for 20-weeks did not cause obvious adverse effects on growth and no statistically significant differences in body weight were observed between groups. However, the weight (mean ± SEM) of pancreas at the end of the study was higher in blank c-SLN group (223.6 ± 42.2 mg) compared to low (138.0 ± 26.0 mg; not significant [NS]), medium (145.0 ± 9.0 mg; NS), and high (133.8 ± 20.3 mg; NS) ACS c-SLN treated groups, demonstrating the efficacy of ACS c-SLN nanoformulations. The low, medium and high dose of ACS c-SLN combinations exhibited a reduction in tumor incidence (PanIN count) by 16.6% (P < 0.01), 66.8% (P < 0.01), and 83.4% (P < 0.01), respectively. These studies provide further proof for the use of an oral, low dose nanotechnology-based combinatorial regimen for the chemoprevention of PDAC.

Adapting Leadership Styles to Reflect Generational Differences in the Academy.

The topic of adapting one's leadership style is controversial and can generate great debate. When one considers adapting one's leadership style, the question of authenticity often bubbles to the surface. This is even more compelling in the context of generational differences in our society and workforce. How can faculty members be effective if they refuse to adapt their leadership style to students' learning styles and generational characteristics? Leadership development is an ongoing focus for the American Association of Colleges of Pharmacy (AACP) to prepare faculty for roles as future leaders in higher education while a major redistribution of generations is occurring within the workforce. These generations are molded by many factors, including the economy, significant events, technology, and education. As experienced leaders, we affirm that one's leadership styles must be honed over time and adapted to reflect generational differences in academic pharmacy among colleagues, students, alumni, and stakeholders, including patients. Current and future leaders need further education and development so that their awareness of generational characteristics prepares them to adapt their leadership styles to more effectively engage and lead people of any generation.

Multiproduct Resin Reuse for Clinical and Commercial Manufacturing-Methodology and Acceptance Criteria.

Chromatography resins used for purifying biopharmaceuticals are generally dedicated to a single product. In good manufacturing practice (GMP) facilities that manufacture a limited amount of any particular product, this practice can result in the resin being used for a fraction of its useful life. A methodology for extending resin reuse to multiple products is described. With this methodology, resin and column performance, product carryover, and cleaning effectiveness are continually monitored to ensure that product quality is not affected by multiproduct resin reuse (MRR). Resin and column performance is evaluated in terms of (a) system suitability parameters, such as peak-shape and transition, and height equivalent theoretical plate (HETP) data; (b) key operating parameters, such as flow rate, inlet pressure, and pressure drop across the column; and (c) process performance parameters, such as impurity profiles, product quality, and yield. Historical data are used to establish process capability limits (PCLs) for these parameters. Operation within the PCLs provides assurance that column integrity and binding capacity of the resin are not affected by MRR.Product carryover defined as the carryover of the previously processed product (A) into a dose of the subsequently processed product (B) (COA→B), should be acceptable from a predictive patient safety standpoint. A methodology for determining COA→B from first principles and setting acceptance limits for cleaning validation is described.Cleaning effectiveness is evaluated by performing a blank elution run after inter-campaign cleaning and prior to product changeover. The acceptance limits for product carryover (COA→B) are more stringent for MRR than for single-product resin reuse. Thus, the inter-campaign cleaning process should be robust enough to consistently meet the more stringent acceptance limits for MRR. Additionally, the analytical methods should be sensitive enough to adequately quantify the concentration of the previously processed product (A) and its degradants in the eluent.General considerations for designing small-scale chromatographic studies for process development are also described. These studies typically include process-cycling runs with multiple products followed by viral clearance studies with a panel of model viruses. Small-scale studies can be used to optimize cleaning parameters, predict resin performance and product quality, and estimate the number of multiproduct purification cycles that can be run without affecting product quality. The proposed methodology is intended to be broadly applicable; however, it is acknowledged that alternative approaches may be more appropriate for specific scenarios.LAY ABSTRACT: Chromatography resins used for purifying biopharmaceuticals are generally dedicated to a single product. In good manufacturing practice (GMP) facilities that make a limited amount of any particular product, this practice can result in the resin being used for a fraction of its useful life. A methodology for extending resin reuse to multiple products is described. With this methodology, resin and column performance, product carryover, and cleaning effectiveness are continually monitored to ensure that product quality is not affected by multiproduct resin reuse.General considerations for designing small-scale chromatographic studies for process development are described. These studies typically include process-cycling runs with multiple products followed by viral clearance studies with a panel of model viruses. Small-scale studies can be used to optimize cleaning parameters, predict resin performance and product quality, and estimate the number of multiproduct purification cycles that can be run without impacting product quality.The proposed methodology is intended to be broadly applicable; however, it is acknowledged that alternative approaches may be more appropriate for specific scenarios.

An analysis of the use of Pharmacy Curriculum Outcomes Assessment (PCOA) scores within one professional program.

OBJECTIVE: The Pharmacy Curriculum Outcomes Assessment (PCOA) is a recent assessment requirement for US pharmacy professional programs. This study analyses PCOA scores for uses described in the 2016 Standards with data from one professional program. METHODS: PCOA data were analyzed for two consecutive classes (n=215) of pharmacy students at the end of their didactic curriculum to explore relationships among PCOA scores, grade point average (GPA), and North American Pharmacist Licensure Examination (NAPLEX) scores utilizing regression analyses. RESULTS: Decisions about student learning based on PCOA scores and GPA indicated remediation would have been prescribed for approximately 7% of students. In comparison, NAPLEX scores revealed a 1% failure rate among the study sample. Relationships between PCOA scores and GPA (r=0.47) and NAPLEX (r=0.51) were moderate to large, respectively. GPA explained a larger portion of unique variance (14%) than PCOA (8%) in NAPLEX scores. CONCLUSIONS: In this sample of students, academic decisions would have varied depending upon the learning assessment, which is consistent with a moderate correlation between GPA and PCOA scores. Although PCOA scores correlate with GPA and NAPLEX, PCOA scores explained a smaller portion of unique variance in NAPLEX scores than GPA. The ongoing establishment of validity evidence of PCOA scores is important for meaningful interpretation of scores for the intended uses.

Triptolide and celastrol loaded silk fibroin nanoparticles show synergistic effect against human pancreatic cancer cells.

Pancreatic cancer is a lethal disease with a dreadful 5-year survival rate of only 5%. In spite of several treatment options, the prognosis still remains extremely poor. Therefore, novel therapy strategies with combinations of drugs are urgently required to combat this fatal disease. Triptolide (TPL) and celastrol (CL), two main compounds in traditional Chinese medicine isolated from Thunder God Vine, have a broad range of bioactivities including anticancer activity. Silk fibroin (SF), a naturally occurring protein with several unique properties, is an ideal carrier material. In this study, we prepared TPL and CL loaded silk fibroin nanoparticles (TPL-SFNPs and CL-SFNPs) by a modified desolvation method and evaluated their synergistic effects against human pancreatic cancer cells. Both SFNPs were characterized for particle size and zeta potential. The entrapment efficiency, drug loading, and drug release profiles were evaluated by HPLC. The cytotoxicity and synergistic effect of SFNPs were investigated in MIA PaCa-2 and PANC-1 human pancreatic cells. The results showed that the particle sizes of TPL-SFNPs and CL-SFNPs were 166.4 ± 4.6 nm and 170.4 ± 2.3 nm, with a mean zeta potential -27.2 ± 2.0 mV and -25.5 ± 2.57 mV, respectively. TPL-SFNPs and CL-SFNPs have a drug loading of 57.0 ± 4.7 µg mg-1 and 63.5 ± 3.8 µg mg-1 along with an encapsulation efficiency of 81.8 ± 2.8% and 87.0 ± 5.1%, respectively. Drug release studies revealed that a rapid release of the drugs from SFNPs was observed at pH 4.5 (lysosomal pH) and a delayed release was observed at pH 7.4 (plasma pH). TPL-SFNPs (IC50 3.80 and 4.75 nM) and CL-SFNPs (IC50 0.38 and 0.64 µM) were 2-3 fold more potent against MIA PaCa-2 and PANC-1 cells than free TPL (IC50 11.25 and 11.58 nM) and CL (IC50 0.84 and 1.23 µM). Furthermore, co-treatment with TPL-SFNPs and CL-SFNPs increased the growth inhibition of the same cells significantly in comparison with TPL-SFNPs or CL-SFNPs alone. Almost all combination index (CI) values, calculated using the CompuSyn software, were <1, suggesting that the growth inhibition effect of TPL-SFNPs in combination with CL-SFNPs was synergistic rather than additive, further suggesting that this novel combination may offer a potential treatment for pancreatic cancer.

Imiquimod-induced psoriasis-like inflammation in differentiated Human keratinocytes: Its evaluation using curcumin.

Psoriasis is considered to be a systemic disease of immune dysfunction. It is still unclear what triggers the inflammatory cascade associated with psoriasis but recent evidences suggest the vital role of IL-23/IL-17A cytokine axis in etiology of psoriasis. Several studies have been conducted in psoriatic-like animal models but ethical issues and complexity surrounding it halts the screening of new anti-psoriatic drug candidates. Hence, in this study, we developed a new in-vitro model for psoriasis using imiquimod (IMQ) induced differentiated HaCaT cells which could be used for screening of new anti-psoriatic drug candidates. The differentiated HaCaT cells were treated with IMQ (100µM) to induce psoriatic like inflammation and its effect was investigated using a natural anti-psoriatic compound, curcumin. The proliferation of psoriatic-like cells was inhibited by curcumin at 25 and 50µM concentrations. The psoriatic-like cells decreased in number with increase in apoptotic and dead cells upon curcumin treatment. Curcumin inhibited the proliferation of IMQ-induced differentiated HaCaT cells (Psoriatic-like cells) by down-regulation of pro-inflammatory cytokines, interleukin-17, tumor necrosis factor-α, interferon-γ, and interleukin-6. Apart from this, curcumin significantly enhanced the skin-barrier function by up-regulation of involucrin (iNV) and filaggrin (FLG), the regulators of epidermal skin barrier. The IMQ-induced differentiated HaCaT in vitro model recapitulated some aspects of the psoriasis pathogenesis similar to murine model. Henceforth, we conclude that this model may be used for rapid screening of anti-psoriatic drug candidates and warrant further mechanistic studies.

Preclinical systemic toxicity evaluation of chitosan-solid lipid nanoparticle-encapsulated aspirin and curcumin in combination with free sulforaphane in BALB/c mice.

Our previous studies have established the efficacy of chemopreventive regimens of aspirin and curcumin (CUR) encapsulated within solid lipid nanoparticles (SLNs) in combination with free sulforaphane (ACS combination) to prevent or delay the initiation and progression of pancreatic cancer, classified as one of the deadliest diseases with very low chances of survival upon diagnosis. Although toxicity of individual drugs and SLN has been studied previously, there are no studies in current literature that evaluate the potential toxicity of a combined regimen of ACS, especially when encapsulated within chitosan-SLNs (c-SLNs). Hence, objective of the current study was to investigate the potential toxic effects of ACS c-SLN combined chemopreventive regimens following acute (3 days), subacute (28 days), and subchronic (90 days) administrations by oral gavage in BALB/c mice. Mice were administered the following regimens: saline, blank c-SLN, low-dose ACS c-SLN (2+4.5+0.16 mg/kg), medium-dose ACS c-SLN (20+45+1.6 mg/kg), and high-dose ACS c-SLN (60+135+4.8 mg/kg). The potential toxicity was evaluated based on animal survival, body weight, hematology, blood chemistry, and organ histopathology. During 3-day, 28-day, and 90-day study periods, no animal deaths were observed. Treatment with ACS c-SLNs did not cause alteration in complete blood counts and blood chemistry data. Histopathological examination of various organ sections (pancreas, heart, liver, kidney, and brain) appeared normal. Based on the results of this study, no signs of toxicity in acute, subacute, and subchronic studies following oral administration of ACS c-SLNs were found indicating that the oral dosing regimens were safe at the levels tested for long-term administration to prevent the onset of pancreatic cancer.

Protective Effects of Triphala on Dermal Fibroblasts and Human Keratinocytes.

Human skin is body's vital organ constantly exposed to abiotic oxidative stress. This can have deleterious effects on skin such as darkening, skin damage, and aging. Plant-derived products having skin-protective effects are well-known traditionally. Triphala, a formulation of three fruit products, is one of the most important rasayana drugs used in Ayurveda. Several skin care products based on Triphala are available that claim its protective effects on facial skin. However, the skin protective effects of Triphala extract (TE) and its mechanistic action on skin cells have not been elucidated in vitro. Gallic acid, ellagic acid, and chebulinic acid were deduced by LC-MS as the major constituents of TE. The identified key compounds were docked with skin-related proteins to predict their binding affinity. The IC50 values for TE on human dermal fibroblasts (HDF) and human keratinocytes (HaCaT) were 204.90 ± 7.6 and 239.13 ± 4.3 µg/mL respectively. The antioxidant capacity of TE was 481.33 ± 1.5 mM Trolox equivalents in HaCaT cells. Triphala extract inhibited hydrogen peroxide (H2O2) induced RBC haemolysis (IC50 64.95 µg/mL), nitric oxide production by 48.62 ± 2.2%, and showed high reducing power activity. TE also rescued HDF from H2O2-induced damage; inhibited H2O2 induced cellular senescence and protected HDF from DNA damage. TE increased collagen-I, involucrin and filaggrin synthesis by 70.72 ± 2.3%, 67.61 ± 2.1% and 51.91 ± 3.5% in HDF or HaCaT cells respectively. TE also exhibited anti-tyrosinase and melanin inhibition properties in a dose-dependent manner. TE increased the mRNA expression of collagen-I, elastin, superoxide dismutase (SOD-2), aquaporin-3 (AQP-3), filaggrin, involucrin, transglutaminase in HDF or HaCaT cells, and decreased the mRNA levels of tyrosinase in B16F10 cells. Thus, Triphala exhibits protective benefits on skin cells in vitro and can be used as a potential ingredient in skin care formulations.

Process and Performance Outcomes of a Nontraditional Postbaccalaureate PharmD Program Geared Toward Internationally Trained Pharmacists.

Established in 2003, the fully accredited international postbaccalaureate doctor of pharmacy (IPBP) program has attracted internationally trained pharmacists from approximately 25 countries and 6 continents, mostly residents of the United States, to attain the doctor of pharmacy (PharmD) degree at the Western University of Health Sciences. While recent trends in the IPBP applicant pool have shown a decline from its peak numbers in 2009 (222 applicants) for the 20 available seats each year, the quality of students remains high. Benchmark measures assessed for this group of students include the internal assessment entrance examination, admissions scores, academic assessments from didactic blocks, and scores on the North American Pharmacy Licensure Examination (NAPLEX), all of which indicate this quality. Moreover, graduates from the program not only consistently demonstrate excellence in the pharmacy curriculum and board examinations, but also go on to establish themselves as competent practitioners and educators. While the long-term future of the program is unknown, the status of the program and its graduates provides ample evidence of its value and ensures its continued success going forward.

Ferulic acid combined with aspirin demonstrates chemopreventive potential towards pancreatic cancer when delivered using chitosan-coated solid-lipid nanoparticles.

BACKGROUND: The overall goal of this study was to demonstrate potential chemopreventive effects of ferulic acid (FA), an antioxidant, combined with aspirin (ASP), a commonly used anti-inflammatory drug for pancreatic cancer chemoprevention, using a novel chitosan-coated solid lipid nanoparticles (c-SLN) drug delivery system encapsulating FA and ASP. RESULTS: Our formulation optimization results showed that c-SLNs of FA and ASP exhibited appropriate initial particle sizes in range of 183 ± 46 and 229 ± 67 nm, encapsulation efficiency of 80 and 78 %, and zeta potential of 39.1 and 50.3 mV, respectively. In vitro studies were conducted to measure growth inhibition and degree of apoptotic cell death induced by either FA or ASP alone or in combination. Cell viability studies demonstrated combinations of low doses of free FA (200 µM) and ASP (1 mM) significantly reduced cell viability by 45 and 60 % in human pancreatic cancer cells MIA PaCa-2 and Panc-1, respectively. However, when encapsulated within c-SLNs, a 5- and 40-fold decreases in dose of FA (40 µM) and ASP (25 µM) was observed which was significant. Furthermore, increased apoptosis of 35 and 31 % was observed in MIA PaCa-2 and Panc-1 cells, respectively. In vivo studies using oral administration of combinations of 75 and 25 mg/kg of FA and ASP c-SLNs to MIA PaCa-2 pancreatic tumor xenograft mice model suppressed the growth of the tumor by 45 % compared to control, although this was not statistically significant. In addition, the immunohistochemical analysis of tumor tissue showed significant decrease in expression of proliferation proteins PCNA and MKI67, and also increased expression of apoptotic proteins p-RB, p21, and p-ERK1/2 indicating the pro-apoptotic role of the regimen. CONCLUSION: Combination of FA and ASP delivered via a novel nanotechnology-based c-SLN formulation demonstrates potential for pancreatic cancer chemoprevention and could be a promising area for future studies.

Evaluation of ibuprofen loaded solid lipid nanoparticles and its combination regimens for pancreatic cancer chemoprevention.

The objective of the present study was to establish the individual and combined chemopreventive potential of a widely used non-steroidal anti-inflammatory drug, ibuprofen (IBU), encapsulated in solid lipid nanoparticles (SLNs) for the chemoprevention of pancreatic cancer. The IBU SLNs were optimized using various lipids (Stearic acid, Compritol 888 ATO and Tripalmitin) and surfactants (Poloxamer 188, Tween-80). The synergistic effect of combination of IBU with sulforaphane (SFN) was also evaluated. Cell viability studies were conducted followed by colony formation and NF-κB DNA binding assays. The IC50 concentration of free IBU in human pancreatic cancer Panc-1 and MIA PaCa-2 cells were 1.25 and 1.26 mM, respectively. SLN optimization study of IBU revealed stearic acid (1:2 drug to lipid ratio) formulated with Poloxamer 188 to be the most efficacious in cell viability study. Upon encapsulation in SLNs, IC50 concentration of IBU-SLN was 113.8 and 122.6 µM for Panc-1 and MIA PACa-2 cells, respectively, reflecting a 10-fold reduction compared to free IBU. Combinations of low doses of free IBU (250 µM) and SFN (5 µM) reduced cell viability by ~55% (P<0.01), whereas a lower dose of encapsulated IBU-SLN (62.5 µM) and free SFN (5 µM) reduced cell viability by ~80% (P<0.001) for both Panc-1 and MIA PaCa-2 cells. These results reflect 4-fold reduction in IBU-SLN dose in combination compared to free IBU. Moreover, IBU-SLN and free SFN combination reduced number of colonies by ~50% (P<0.01). Further, IBU-SLN and SFN combinations showed down-regulation of DNA binding activity of the p50 subunit of NF-κB. In conclusion, these preliminary results demonstrate the potential of IBU as a chemopreventive agent against pancreatic cancer. Furthermore, when encapsulated in nanotechnology-based SLN delivery systems and delivered in combination with SFN provide evidence of a promising approach for pancreatic cancer prevention and therapy.