The structural, optical and photovoltaic properties of Zn-doped MAPbI2Br perovskite solar cells.

The spin coating method was used to deposit MAPbI2Br films on FTO-glass substrates. Zn2+ (zinc) doping was used for these films at intensity rates of 2% and 4%, respectively. XRD analysis proved that MAPbI2Br films had a cubic structure and a crystalline character. 2% Zn doping into the MAPbI2Br film had a modest large grain size (38.09 nm), Eg (1.95 eV), high refractive index (2.66), and low extinction coefficient (1.67), according to XRD and UV-vis analyses. To facilitate and enhance carrier transit, at contacts as well as throughout the bulk material, the perovskite's trap-state densities decreased. The predicted MAPbI2Br valence and conduction band edges are -5.44 and -3.52, respectively. The conduction band (CB) edge of the film that was exposed to Zn atoms has been pressed towards the lower value, assembly it a better material for solar cells. EIS is particularly useful for understanding charge carrier transport, recombination mechanisms, and the influence of different interfaces within the device structure. Jsc is 11.09 mA cm-2, Voc is 1.09, PCE is 9.372% and FF is 0.777. The cell made with the 2% Zn doped into the MAPbI2Br film demonstrated a superior device.

Bandgap reduction and efficiency enhancement in Cs2AgBiBr6 double perovskite solar cells through gallium substitution.

Lead-free halide double perovskite (LFHDP) Cs2AgBiBr6 has emerged as a promising alternative to traditional lead-based perovskites (LBPs), offering notable advantages in terms of chemical stability and non-toxicity. However, the efficiency of Cs2AgBiBr6 solar cells faces challenges due to their wide bandgap (Eg). As a viable strategy to settle this problem, we consider optimization of the optical and photovoltaic properties of Cs2AgBiBr6 by Gallium (Ga) substitution. The synthesized Cs2Ag0.95Ga0.05BiBr6 is rigorously characterized by means of X-ray diffraction (XRD), UV-vis spectroscopy, and solar simulator measurements. XRD analysis reveals shifts in peak positions, indicating changes in the crystal lattice due to Ga substitution. The optical analysis demonstrates a reduction in the Eg, leading to improvement of the light absorption within the visible spectrum. Importantly, the Cs2Ag0.95Ga0.05BiBr6 solar cell exhibits enhanced performance, as evidenced by higher values of open circuit voltage (Voc), short-circuit current (Jsc), and fill factor (FF), which are 0.94 V, 6.01 mA cm-2, and 0.80, respectively: this results in an increased power conversion efficiency (PCE) from 3.51% to 4.52%. This research not only helps to overcome film formation challenges, but also enables stable Cs2Ag0.95Ga0.05BiBr6 to be established as a high-performance material for photovoltaic applications. Overall, our development contributes to the advancement of environmentally friendly solar technologies.

Impact of Ce doping on the optoelectronic and structural properties of a CsPbIBr2 perovskite solar cell.

This paper provides a detailed analysis of pure CsPbIBr2 and 4% Ce-doped CsPbIBr2 perovskite films, emphasizing their structural, optical and photovoltaic properties. X-ray diffraction confirms a predominant cubic perovskite phase in both samples, with Ce doping leading to the increased crystal size (21 nm to 32 nm). UV-vis spectroscopy reveals a reduced bandgap energy (2.2 eV to 2.1 eV) with Ce doping. Dielectric constant analysis indicates the enhanced permittivity of the Ce-doped sample, crucial for solar-cell light trapping. Energy band structure analysis demonstrates improved photovoltaic cell performance with Ce doping, yielding higher open-circuit voltage, short-circuit current, and efficiency (9.71%) compared to pure CsPbIBr2 (8.02%). Ce doping mitigates electron-hole recombination, enhancing cell stability, electron affinity, and power output. This research underscores the potential of cost-effective, efficient, and stable CsPbIBr2 perovskite solar cells.

Celecoxib and bevacizumab synergistically inhibit non-small cell lung cancer by inducing apoptosis and modulating VEGF and MMP-9 expression.

Lung cancer is the most typical form of cancer that results in death worldwide. Patients with non-small cell lung cancer (NSCLC) have an around 15% survival rate despite of advancement in cancer treatment. This study aimed to evaluate the combined effect of celecoxib and bevacizumab on NSCLC using A549 cells as an in vitro model. The A549 cells were culture and treated with celecoxib, bevacizumab and their combination and the cell proliferation was assessed using MTT assay, whereas cell apoptosis was analyzed using flowcytometry. The effects on the apoptotic genes were examined using western blotting, while qPCR was used for analyzing the VEGF and MMP-9 expression. Celecoxib, bevacizumab and their combination exhibited a dose dependent inhibition (p<0.001). The rate of apoptosis was 14.1% and 26.5% but when the two drugs were combined, the rate of apoptosis was significantly increased due to synergism by 52.2% (p<0.001). Western blotting displayed that co-treatment significantly up regulated proapoptotic genes (caspase-3 and -9) and down regulated anti-apoptotic gene (Bcl-2) (p<0.001). Additionally, VEGF and MMP-9 expression were both significantly reduced with co-treatment compared to the control (p<0.001). Celecoxib combined with bevacizumab synergistically inhibited NSCLC by inducing apoptosis and modulating VEGF and MMP-9 expression.

Frequency, Characteristics, and Risk Factors for Falls at an Inpatient Cancer Rehabilitation Unit.

PURPOSE: Falls in the hospital can lead to adverse events, including injuries. Studies have shown that patients with cancer and those undergoing inpatient rehabilitation (IPR) are at higher risk for falls. Therefore, we measured the frequency, degree of harm, and characteristics of patients who fell in an inpatient cancer rehabilitation unit. METHODS: A retrospective review was conducted on inpatient cancer rehabilitation patients admitted from January 2012 to February 2016. Fall frequency, degree of harm, fall circumstances, cancer type, patient's fall risk score on the basis of the MD Anderson Cancer Center Adult Inpatient Fall Risk Assessment Tool (MAIFRAT), length of stay, and risk factors were evaluated for patients. RESULTS: There were 72 out of 1,571 unique individual falls (4.6%), with a falls incidence of 3.76 falls per 1,000 patient-days. Most fallers (86%) suffered no harm. Risk factors for falls included presence of patient-controlled analgesia pump (P = .03), pump such as insulin or wound vacuum-assisted closure (P < .01), nasogastric, gastric, or chest tube (P = .05), and higher MAIFRAT score (P < .01). The fallers were younger (62 v 66; P = .04), had a longer IPR stay (13 v 9; P = .03), and had a lower Charlson comorbidity index (6 v 8; P < .01). CONCLUSION: The frequency and degree of harm for falls in the IPR unit were less than previous studies, which suggests that mobilization for these patients with cancer is safe. The presence of certain medical devices may contribute to fall risk, and more research is needed to better prevent falls in this higher-risk subgroup.

Potential therapeutic strategies for myocardial infarction: the role of Toll-like receptors.

Myocardial infarction (MI) is a life-threatening condition among patients with cardiovascular diseases. MI increases the risk of stroke and heart failure and is a leading cause of morbidity and mortality worldwide. Several genetic and epigenetic factors contribute to the development of MI, suggesting that further understanding of the pathomechanism of MI might help in the early management and treatment of this disease. Toll-like receptors (TLRs) are well-known members of the pattern recognition receptor (PRR) family and contribute to both adaptive and innate immunity. Collectively, studies suggest that TLRs have a cardioprotective effect. However, prolonged TLR activation in the response to signals generated by damage-associated molecular patterns (DAMPs) results in the release of inflammatory cytokines and contributes to the development and exacerbation of myocardial inflammation, MI, ischemia-reperfusion injury, myocarditis, and heart failure. The objective of this review is to discuss and summarize the association of TLRs with MI, highlighting their therapeutic potential for the development of advanced TLR-targeted therapies for MI.

Development of Natural Polysaccharide-Based Nanoparticles of Berberine to Enhance Oral Bioavailability: Formulation, Optimization, Ex Vivo, and In Vivo Assessment.

The phytogenous alkaloid berberine (BBR) has become a potential drug for the treatment of diabetes, hyperlipidemia, and cancer. However, its therapeutic potential is limited because ofpoor intestinal absorption due to its efflux by the P-gp expressed in the intestinal lumen. Therefore, we aimed to design and fabricate a nanoparticulate system for delivery of BBR employing naturally derived biodegradable and biocompatible polymers, mainly chitosan and alginate, to enhance the oral bioavailability of BBR. A chitosan-alginate nanoparticle system loaded with BBR (BNPs) was formulated by ionic gelation method and was optimized by employing a three-factor, three-level Box-Behnken statistical design. BNPs were characterized for various physicochemical properties, ex vivo, and in vivo evaluations. The optimized BNPs were found to be 202.2 ± 4.9 nm in size, with 0.236 ± 0.02 of polydispersity index, zeta potential -14.8 ± 1.1 mV, and entrapment efficiency of 85.69 ± 2.6%. BNPs showed amorphous nature with no prominent peak in differential scanning calorimetry (DSC) investigation. Similarly, fourier-transform infrared spectroscopy (FTIR) studies did not reveal any interaction between BBR and excipients used. The drug release followed Higuchi kinetics, since these plots demonstrated the highest linearity (R2 = 0.9636), and the mechanism of release was determined to be anomalous or non-Fickian in nature. An ex-vivo gut permeation study showed that BNPs were better internalized into the cells and more highly permeated through the intestine. Furthermore, in vivo pharmacokinetic analysis in female Wistar rats showed a 4.10-fold increase in the oral bioavailability of BBR from BNPs as compared to BBR suspension. With these findings, we have gained new insight into the effective delivery of poorly soluble and permeable drugs via a chitosan-alginate nanoparticle system to improve the therapeutic performance of an oral nanomedicine.

Hypertriglyceridemia-Induced Pancreatitis Complicated by Diabetic Ketoacidosis.

Acute pancreatitis is a potentially fatal clinical entity having multiple underlying triggers. Though the incidence of hypertriglyceridemia-induced pancreatitis is low; however, patients with such risk factors develop severe disease. We present a case of a 47-year-old male who came to our facility with complaints of epigastric pain. Physical examination and laboratory workup unmasked the presence of pancreatitis alongside concurrent diabetic ketoacidosis (DKA). This presentation is unique, and to our knowledge, only a few cases have been reported in the literature. Furthermore, the co-existence of pancreatitis and DKA can overlap the clinical picture of each other, which might lead to unwanted complications if not diagnosed timely.

The development of a nomogram to determine the frequency of elevated risk for non-medical opioid use in cancer patients.

OBJECTIVE: Non-medical opioid use (NMOU) is a growing crisis. Cancer patients at elevated risk of NMOU (+risk) are frequently underdiagnosed. The aim of this paper was to develop a nomogram to predict the probability of +risk among cancer patients receiving outpatient supportive care consultation at a comprehensive cancer center. METHOD: 3,588 consecutive patients referred to a supportive care clinic were reviewed. All patients had a diagnosis of cancer and were on opioids for pain. All patients were assessed using the Edmonton Symptom Assessment Scale (ESAS), Screener and Opioid Assessment for Patients with Pain (SOAPP-14), and CAGE-AID (Cut Down-Annoyed-Guilty-Eye Opener) questionnaires. "+risk" was defined as an SOAPP-14 score of ≥7. A nomogram was devised based on the risk factors determined by the multivariate logistic regression model to estimate the probability of +risk. RESULTS: 731/3,588 consults were +risk. +risk was significantly associated with gender, race, marital status, smoking status, depression, anxiety, financial distress, MEDD (morphine equivalent daily dose), and CAGE-AID score. The C-index was 0.8. A nomogram was developed and can be accessed at https://is.gd/soappnomogram. For example, for a male Hispanic patient, married, never smoked, with ESAS scores for depression = 3, anxiety = 3, financial distress = 7, a CAGE score of 0, and an MEDD score of 20, the total score is 9 + 9+0 + 0+6 + 10 + 23 + 0+1 = 58. A nomogram score of 58 indicates the probability of +risk of 0.1. SIGNIFICANCE OF RESULTS: We established a practical nomogram to assess the +risk. The application of a nomogram based on routinely collected clinical data can help clinicians establish patients with +risk and positively impact care planning.

Endoxifen: A new, protein kinase C inhibitor to treat acute and mixed mania associated with bipolar I disorder.

OBJECTIVES: Endoxifen is a protein kinase C inhibitor. The objective of the present phase III study was to demonstrate the safety and efficacy of endoxifen in treating bipolar I disorder (BPD I) patients. METHODS: A multicenter, double-blind, active-controlled study was conducted using a daily dose of 8 mg endoxifen compared to 1000 mg divalproex, the current standard treatment, in patients with BPD I acute manic episodes with/without mixed features. The primary endpoint of our study was the mean change in total Young Mania Rating Scale (YMRS) score at day 21. RESULTS: Endoxifen (n = 116) significantly (p < 0.0001) reduced total YMRS score (from 33.1 to 17.8. A significant (p < 0.001) improvement in Montgomery-Åsberg Depression Rating Scale (MADRS) score was observed for endoxifen (4.8 to 2.5). Early time to remission of the disease was observed with endoxifen compared to divalproex. None of the patients required rescue medication and there was no drug-associated withdrawals. Changes in Clinical Global Impressions-Bipolar Disorder and Clinical Global Impression-Severity of Illness scores showed that treatment with endoxifen was well-tolerated. CONCLUSIONS: Endoxifen at a low daily dose of 8 mg was as efficacious and safe in patients with BPD I acute manic episodes with/without mixed features.

Efficacy and safety of nanosomal docetaxel lipid suspension based chemotherapy in gastric and gastroesophageal junction adenocarcinoma.

The current retrospective multicenter study evaluated the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS; DoceAqualip) based chemotherapy in patients with gastric and gastroesophageal junction (GEJ) adenocarcinoma. The medical charts of patients with gastric and GEJ adenocarcinoma, who were treated with NDLS (50-75 mg/m2; 3 weekly cycles) based chemotherapy and followed-up from April 2014 to September 2018, were analyzed. The study endpoints included overall response rate (ORR) and disease control rate (DCR) in neoadjuvant and metastatic settings. Overall survival (OS) and safety were also evaluated. Of the 43 patients with gastric (n=39) and GEJ (n=4) adenocarcinoma, efficacy evaluation was available in 35 (neoadjuvant, 17/18 patients; metastatic, 18/25 patients). In the neoadjuvant setting, an ORR of 58.82% and a DCR of 94.11% were observed, whereas in the metastatic setting, the ORR was 77.77% and the DCR was 83.33%. In the neoadjuvant setting, at a follow-up ranging from 0.7 to 41.2 months, the median OS was not reached. In the metastatic setting, the median OS was 31.9 months at a follow-up ranging from 0.2 to 50.3 months. At least one adverse event (AE) was reported in 24 patients. Anemia, lymphopenia and thrombocytopenia were the most common hematological AEs, while nausea, vomiting and weakness were the most common non-hematological AEs. NDLS based treatment was well-tolerated without any new safety concerns. Overall, NDLS-based chemotherapy was effective and well-tolerated in the management of gastric and GEJ adenocarcinoma.

The Development of Pemetrexed Diacid-Loaded Gelatin-Cloisite 30B (MMT) Nanocomposite for Improved Oral Efficacy Against Cancer: Characterization, In-Vitro and Ex-Vivo Assessment.

AIM: The intention of this investigation was to develop Pemetrexed Diacid (PTX)-loaded gelatine-cloisite 30B (MMT) nanocomposite for the potential oral delivery of PTX and the in vitro, and ex vivo assessment. BACKGROUND: Gelatin/Cloisite 30 B (MMT) nanocomposites were prepared by blending gelatin with MMT in aqueous solution. METHODS: PTX was incorporated into the nanocomposite preparation. The nanocomposites were investigated by Fourier Transmission Infra Red Spectroscopy (FT-IR), Differential Scanning Calorimetry (DSC), Scanning Electron Microscope (SEM) X-Ray Diffraction (XRD) and Confocal Laser Microscopy (CLSM). FT-IR of nanocomposite showed the disappearance of all major peaks which corroborated the formation of nanocomposites. The nanocomposites were found to have a particle size of 121.9 ± 1.85 nm and zeta potential -12.1 ± 0.63 mV. DSC thermogram of drug loaded nanocomposites indicated peak at 117.165 oC and 205.816 oC, which clearly revealed that the drug has been incorporated into the nanocomposite because of cross-linking of cloisite 30 B and gelatin in the presence of glutaraldehyde. RESULTS: SEM images of gelatin show a network like structure which disappears in the nanocomposite. The kinetics of the drug release was studied in order to ascertain the type of release mechanism. The drug release from nanocomposites was in a controlled manner, followed by first-order kinetics and the drug release mechanism was found to be of Fickian type. CONCLUSION: Ex vivo gut permeation studies revealed 4 times enhancement in the permeation of drug present in the nanocomposite as compared to plain drug solution and were further affirmed by CLSM. Thus, gelatin/(MMT) nanocomposite could be promising for the oral delivery of PTX in cancer therapy and future prospects for the industrial pharmacy.

Optimisation of ethosomal nanogel for topical nano-CUR and sulphoraphane delivery in effective skin cancer therapy.

Aim: The optimisation and evaluation of ethosomal nanogel (NGs) for topical delivery in skin cancer.Methods: The formulations were optimised by employing 3-factor, 3-level Box Behnken design for responses of vesicle size, and fluxes. They characterised in vitro and evaluated for drug release, permeation and retention, skin penetration of ethosome, electron microscopy, texture analysis, and in vitro cytotoxicity.Results: The optimised formulation exhibited z-average 125.67 ± 10.43 nm, apparent zeta potential -17.1 ± 2.61 mV, average flux of drug loaded ethosome were 54.72 ± 5.45 and 59.83 ± 6.09 µg/cm2/h. Further, Rhodamine B loaded ethosome penetrated deeper up to 183.82 µm. The NGs texture analysis showed index of viscosity 225.45 g.s, firmness 209.34 g, cohesiveness -189.48 g, and consistency 59.45 g.s. The optimised ethosome NGs exhibited significant anti-cancer effect in B16-F10 murine tumour cell line (p < 0.05).Conclusion: Ethosomal NGs could be promising for skin cancer treatment.

Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Sarcoma: A Multicenter, Retrospective Study.

OBJECTIVE: To evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip) based chemotherapy in patients with sarcoma. METHODS: In this retrospective, multicenter (6 centers), observational study, we analyzed the medical charts of adult patients of either sex, who were treated with NDLS (75 mg/m2 in 3-weekly cycles) based chemotherapy for the treatment of sarcoma. The efficacy outcomes were overall response rate (ORR: complete response (CR) + partial response (PR)) and disease control rate (DCR: CR + PR + stable disease (SD)) in patients who received NDLS-based chemotherapy in neoadjuvant and metastatic settings. Overall survival (OS) and safety were evaluated for all settings. RESULTS: Of 11 patients (neoadjuvant: 1, adjuvant: 3, and metastatic: 7) in this study, majority had leiomyosarcoma (63.6%, 7/11) followed by extraskeletal myxoid chondrosarcoma (EMC), high grade pleomorphic sarcoma of mandible, malignant fibrous histiocytoma of right thigh, and osteosarcoma of femur (9.1% each, 1/11 each). NDLS plus gemcitabine combination was used in 10 patients (90.9%), and NDLS plus cyclophosphamide was used in one patient with EMC (9.1%). Efficacy evaluation was performed for 7 patients (neoadjuvant: 1/1; metastatic: 6/7). Complete response was reported in one patient (soft tissue sarcoma of mandible) treated in neoadjuvant setting. In metastatic setting, ORR was 50% and DCR was 66.7% (CR: 16.7% (1/6), PR: 33.3% (2/6), SD: 16.7% (1/6)). At a median follow-up of 6.5 months (range: 0.06-20.2 months), median OS was not reached in neoadjuvant and adjuvant settings, but it was 15.8 months in metastatic setting. At least 1 AE was reported in 7 (63.6%) patients. Neutropenia, thrombocytopenia, lymphopenia, and anemia were the hematological AEs, whereas nausea, vomiting, and diarrhea were the most common nonhematological AEs. NDLS treatment was well tolerated without any new safety concerns. CONCLUSION: Nanosomal docetaxel lipid suspension-based chemotherapy was efficacious and well tolerated in the treatment of sarcoma. Further prospective trials are needed to confirm the data.

Concurrent use of opioids with benzodiazepines or nonbenzodiazepine sedatives among patients with cancer referred to an outpatient palliative care clinic.

BACKGROUND: The concurrent use of opioids with benzodiazepines (BZD) or nonbenzodiazepine sedatives (S) recently was found to be associated with an increased risk of overdose death compared with the use of opioids alone. In the current study, the authors examined the frequency and trend of concurrent opioid/BZD-S use and its associated risk factors among patients with cancer. METHODS: Data regarding the frequency and trend of concurrent opioid/BZD-S use were extracted for 1500 randomly selected patients referred to the outpatient palliative care clinic at The University of Texas MD Anderson Cancer Center between the calendar years of 2011 and 2016. To explore associated risk factors, the authors compared the demographic and clinical predictors of 418 patients each in the concurrent opioid/BZD-S group and opioids-only group. RESULTS: In 2011, at the time of referral to the palliative care clinic, 96 of 221 patients with cancer (43%) were prescribed concurrent opioids/BZD-S. This rate progressively declined to 67 of 217 patients (31%) by 2016 (P = .0008). Patients in the concurrent opioid/BZD-S group had a higher percentage of females (233 individuals; 55% [P = .007]) and whites (323 individuals; 77% [P = .002]), and patients reported higher scores regarding depression (P = .0001), anxiety (P ≤ .0001), drowsiness (P = .048), and worst feeling of well-being (P = .001). The morphine equivalent daily dose was significantly higher in concurrent opioid/BZD-S group (median of 67.5 mg/day [interquartile range (IQR), 30-135 mg/day] vs 60 mg/day [IQR, 30-105 mg/day]; P = .034). Multivariate analysis demonstrated that anxiety (P ≤ .0001), white race (P = .0092), and poor Eastern Cooperative Oncology Group performance status (P = .0017) were significantly associated with concurrent use. CONCLUSIONS: The concurrent use of opioids with BZD-S has declined but continues to be frequent among patients with cancer. Anxiety, white race, and poor Eastern Cooperative Oncology Group performance status were associated with its use. More research is needed to explore which medications can replace these agents.

Analytical Comparison of the Originator Granulocyte-colony Stimulating Factor Filgrastim and its Biosimilars.

PURPOSE: Filgrastim, a recombinant human granulocyte colony-stimulating factor (rhG-CSF) produced in Escherichia coli, is indicated for treatment of neutropenia-related conditions in cancer patients. It has been marketed as Neupogen since 1991. In 2006, biosimilar rhG-CSF products have been approved in the European Union (EU). The aim of this study was to compare quality attributes of the originator filgrastim with its three biosimilars which came from the EU market in 2014 to verify whether their similarity is maintained since their market approval. MATERIALS/METHODS: Spectrophotometric analysis was used to determine protein content in analyzed products. Chromatographic and electrophoretic analyses were applied to verify the presence of high and low-molecular weight impurities. Secondary and tertiary structure of the drugs were investigated with circular dichroism and intrinsic fluorescence. Finally, biological activity of the drugs was assessed using cell proliferation assay. RESULTS: All products displayed protein content close to the label concentration with a ±6% variation. Two oxidized forms and a deamidated form were present at <0.5%. Levels of dimers and other high molecular-weight impurities were similar except for one product, which contained higher amount of the dimer. Profiles and levels of process-related impurities were comparable. The three-dimensional conformation of the molecules with respect to exposed tryptophan residues was similar. The relative potencies of the products were comparable to the reference standard with a ±2% variation. CONCLUSION: This study shows that a high level of similarity is maintained among originator and three biosimilar filgrastims up to 5 years from their first registration in the EU.

Lipid drug conjugate nanoparticle as a potential nanocarrier for the oral delivery of pemetrexed diacid: Formulation design, characterization, ex vivo, and in vivo assessment.

The present work was to develop lipid drug conjugated (LDC) nanoparticles for the potential oral delivery of pemetrexed diacid (PTX) and evaluation of its in vitro, ex vivo and in vivo potentials. The LDC was prepared by salt formation of PTX with stearic acid and followed by cold homogenization technique to produce the LDC nanoparticles. FTIR analysis of LDC proved the presence of amide bond in LDC powder indicating the conjugation between drug and lipid. LDC nanoparticles was found to have particle size 121.9±1.85nm and zeta potential -51.6mV±1.23 and entrapment efficiency 81.0±0.89%. TEM images revealed spherical morphology and were in corroboration with particle size measurements. Ex vivo gut permeation studies revealed a very good enhancement in permeation of drug present in the LDC as compared to plain drug solution and were confirmed by CLSM. MTT assay conformed significant% toxicity at the end of 24h and 48h. Furthermore, the AUC0-24 of PTX from the optimized LDC nanoparticels was found to be 4.22 folds higher than that from PTX suspension on oral administration. Thus, LDC has high potential for the oral delivery of PTX in cancer therapy and future prospects for the industrial purpose.

Validated HPLC method for the pharmacokinetic study of oral extended-release cefpodoxime proxetil chitosan-alginate beads in rabbits.

The aim of this study is to develop a simple and applicable HPLC method for the detection of cefpodoxime acid (CFA) in rabbit plasma after oral administration of cefpodoxime proxetil (CFP) loaded chitosan-alginate (CH-ALG) beads formulation. CFP is a prodrug that is deesterified in vivo to its active metabolite CFA to exhibit antibiotic activity. Chromatographic separation of CFA and internal standard (IS) was achieved by a RP18(C18), Phenomenax®100, (250×4.6mm) with the mobile phase consisting of (0.02mol/l (20mM) ammonium acetate solution and acetonitrile (92:8, v/v, pH=4.6) at a flow rate of 1.0ml/min. The method was validated according to the requirements of US-FDA guidelines for bioanalytical method validation. The linear regression analysis for the calibration plots showed good linear relationship (R2=0.9905) in the working concentration range of 0.5-50µg/ml. The limits of detection and quantification (S/N=3) were 0.069 and 0.136µg/ml. Plasma CFA levels were successfully determined in rabbit with satisfactory precision and accuracy. The analyte was found to be stable after a number of stability studies. The proposed HPLC method was successfully applied to pharmacokinetic study in rabbits for CFP loaded CH-ALG beads and marketed immediate release (IR) tablets. All pharmacokinetic parameters were assessed.

In vitro/in vivo evaluation of HPMC/alginate based extended-release matrix tablets of cefpodoxime proxetil.

The purpose of this research was to assessment of antimicrobial activity and in vitro/in vivo evaluation of cefpodoxime proxetil extended-release (ER) tablet for once daily administration. The tablets were prepared using combination of biodegradable polysaccharides including hydroxypropyl methylcellulose and sodium alginate as matrix material to achieve pH-independent ER release. The tablets were found within the permissible limits for various physicochemical parameters. The in vitro drug release showed that the drug was released over a period of 24h in a sustained release manner. The drug release followed Higuchi kinetics as these plots showed the highest linearity (R(2)=0.9833), but a close relationship was also observed with zero-order kinetics (R(2)=0.9088) and the drug release mechanism was found to be of anomalous or non-Fickian type. Further, in vitro drug release was assessed by antimicrobial assay and it revealed that drug release through 24h periods was above the MIC. In vivo investigation in rabbits showed ER pharmacokinetic profile of cefpodoxime from the matrix tablets. A good correlation of drug absorption in vivo and drug release in vitro (R(2)=0.9785) was observed. These results suggested that the investigated CFP matrix tablets have a potential for extended-release dosage forms.