Technological Innovation in Pharmaceutical Research Vol. 1

Odontonema is a group of tropical plant species used in folklore medicine because of its wide range of pharmacological properties. These plants show a wide variety in habitat-preference and biological types. Most of them are shrubs or herbs, climbing plants; xerophytes and marshy plants are also very common. These plants are known to be anti-bacterial, anti-inflammatory, anti-hypertensive, anti-viral, hepatoprotective, sedative and anti-oxidant. Furthermore, some species have been reported to induce child birth and trigger bronchodilatation. Since this group of plants is associated with a plethora of pharmacological properties, a review of reported medicinally-relevant investigations is warranted. Herein, we review the ethnopharmacology, bioactivity reports, and phytochemistry of the plant species belonging to the genus Odontonema. To compile this review, an extensive literature search was conducted using Google Scholar, SciFinder, ScienceDirect, Web of Science, and Scielo web sites, updated to September 2020. Although there are a number of pharmacological and ethnopharmaco-logical reports on the four species of Odontonema covered in this review, phytochemical profiling of this group of plants is quiet limited. Odontonema strictium was found to be the most phytochemically profiled showing the presence of phytosterols and flavonoids. The anti-inflammatory, anti-bacterial, anti-oxidant, anti-hypertensive and uterine contraction properties must stimulate phytochemical research interests into this genus which could, one day, lead to development and commercialization of a drug from this natural source.

Nutrition is a part of systemic health in maintaining an equilibrium between the healthy and ill status. As a part of our regular diet and intake as supplements it plays a major role in maintaining oral health .this article focuses on role of various nutrients that play a major role in maintain oral health. Nutrient and dietary supplements when added along with clinical or mechanical treatment for various oral diseases yield better results. Clinicians and health care personnel should recommend change in diet plans for additional benefits through the process of treatment

Aims: The genus Achromobacter includes lactose-non-fermenting Gram-negative bacteria that are aerobic, motile (with peritrichous flagella), oxidase and catalase-positive. To assess the prevalence of A. xylosoxidans isolated from non-respiratory tract samples from adult inpatients and outpatients and the antibiotic resistance levels at a tertiary-care teaching hospital in Szeged, Hungary retrospectively, during a 10-year study period.

Study Design: Retrospective microbiological study.

Place and Duration of Study: 1^st of January 2008 - 31^st of December 2017 at the University of Szeged, which is affiliated with the Albert Szent-Györgyi Clinical Center, a primary- and tertiary-care teaching hospital in the Southern Great Plain of Hungary.

Methodology: Data collection was performed electronically. Antimicrobial susceptibility testing (AST) was performed using disk diffusion method and when appropriate, E-tests on Mueller–Hinton agar plates.

Results: During the 10-year study period, a total of 68 individual A. xylosoxidans isolates were identified (6.8±3.6/year, range: 0-11 isolates). The frequency of isolation in the first half of the study period (2008-2017) was n=22, while in 2013-2017, this number was n=46. The majority of isolates (51 out of 68) were from inpatient departments. 32 out of 68 patients were female (female-to-male ratio: 0.89). The susceptibilities of the respective A. xylosoxidans isolates (n=68) were the following: high levels of susceptibility for imipenem and meropenem (n=63; 92.6%), and moxifloxacin (n=55; 80.9%), while higher rates of resistance were detected for sulfamethoxazole/trimethoprim (susceptible: n=36; 52.9%), ciprofloxacin (susceptible: n=40; 58.8%) and almost all isolates were resistant to ceftazidime (susceptible: n=3; 4.4%) and cefepime (n=2; 2.9%).

Conclusion: The existing literature on Achromobacter infections in the context of non-respiratory human infections is scarce, as the incidence of these pathogens in clinically-relevant syndromes in low. It should be noted, that the difficulty in the adequate identification (especially in low-resource settings) may be partly blamed for the infrequent characterization of these bacteria as significant pathogens. The developments in diagnostic technologies in routine clinical microbiology will probably lead to a shift in the isolation frequency of these bacteria in the future.

Sunitinib associated chronic necrotizing cavitary pulmonary aspergillosis has rarely been reported in literature. This article describes a patient with biopsy proven papillary renal cell carcinoma initially treated by radical nephrectomy. He presented about 8 months later with progressively worsening abdominal pain, headache, weight loss of 40 pounds and investigation revealed extensive retroperitoneal and mediastinal lymphadenopathy with brain metastasis. He was evaluated by oncology and started on cycles of sunitinib with dexamethasone, which he took for about 6+ months. He presented to the hospital in respiratory distress requiring intubation and ICU admission and CT scan of thorax revealed a new large consolidation with necrosis and a cavity. Given suspicion of opportunistic fungal infection with sunitinib, he was started on empiric Vancomycin, Zosyn and Voriconazole. He underwent bronchoscopy, bronchoalveolar lavage and cultures revealed Aspergillus flavus. Subsequently serum and BAL (Bronchoalveolar Lavage) galactomannan were reported positive as well. Given poor prognosis, patient’s family elected for comfort measures. Enhanced clinical surveillance and implementation of prophylactic strategies based on risk stratification would aid in the prevention, early diagnosis and management of these infections.

Lantana ukambensis (Vatke) Verdc. (Verbenaceae) and Balanites aegyptiaca (L.) Delile (Zygophyllaceae), are used in African traditional medicine for the treatment of wounds and inflammatory diseases. The purpose of this study is to assess the cytotoxicity, cell cycle arrest, and pro-apoptotic effects of the extracts and fractions of these plants against HCT-116 and HT-29 cells. MTS, crystal violet, Hoechst staining, annexin V/PI and cytometry methods were used in this study. The crude extracts of these plants showed significant cytotoxic effects against HCT-116 and HT-29 cells. The 1-butanol and ethyl acetate fractions of L. ukambensis decreased the G1 phase by 20.53% and 28.47% and increased the G2/M by 23.47% and 25.90%, respectively, on HCT-116. Moreover, the 1-butanol fraction increased the cumulative value of apoptotic cells by 49.77% on HCT-116 and the ethyl acetate fraction increased this value by 53.37% at 15 µg/mL after 48 hours of exposure. In the case of B. aegyptiaca, the ethyl acetate fraction increased G1 phase by 3.83% on HCT-116 and by 8.6% on HT-29, whilst G2/M phase was decreased by 5.63 % on HCT-116 and by 6.62% on HT-29. Moreover, apoptotic cells were increased by 11.4% on HCT-116. The outcome of this study suggests the potential of the ethyl acetate fraction of each plant for the isolation of natural anticancer molecules against colorectal cancer.

Fucoidans are sulphated polysaccharides that can be obtained from brown seaweed and marine invertebrates. They have anti-cancer properties, through their targeting of several signaling pathways and molecular mechanisms within malignant cells. This review describes the chemical structure diversity of fucoidans and their similarity with other molecules such as glycosaminoglycan, which enable them to participation in diverse biological processes. Furthermore, this review summarizes their influence on the development of metastasis and drug resistance, which are the main obstacles to cure cancer. In some cancer types, fucoidans can inhibit metastasis processes including EMT, migration, invasion and MET processes. Finally, this article discusses how fucoidans have been used in clinical trials to evaluate their potential synergy with other anti-cancer therapies.

Purpose: The physiology of mouth enabled so many drugs to delivery through oral route. Oral mucosal drug delivery is another option and promising technique for drug delivery which offers a number of advantages The purpose of this study was to prevent first pass metabolism and increase bioavailability of a drug molecule alfuzosin hydrochloride by embedding in a sustained release buccal film over a period of 8 hours.

Materials and Methods: In the present study sustained release formulation of buccoadhesive films of alfuzosin hydrochloride were developed using polymers HPMC, K100M, sodium alginate, chitosan and the prepared buccoadhesive films were systematically evaluated for in vitro performances. The films were provided with a backing layer of Eudragit RS100 so as to get an unidirectional release pattern. The films were evaluated for their physical characteristics like weight, thickness, content uniformity, folding endurance, bioadhesive strength, surface pH, in vitro drug release, ex vivo buccal permeation studies.

Results: The films, prepared by the solvent casting method, were smooth and elegant in appearance; uniform in thickness, weight, and drug content; and showed good folding endurance. The mechanical properties reveal that the formulations were found to be strong but not brittle. The in vitro release data were fit to different equations and kinetic models viz. zero order, first order, higuchi’s plot and peppas plot. The best mucoadhesive performance and matrix controlled release was exhibited by the formulation A7 (2% HPMC K100 M and 2% chitosan). The correlation coefficient value (r) indicates, the kinetic of drug release was zero order. Stability study of optimized films was done and it was found that both drug and buccal films were stable.

Conclusion: It can be concluded that the present buccal formulation can be an ideal system to improve the bioavailability of the drug by avoiding hepatic first-pass metabolism. The optimized buccoadhesive films of alfuzosin hydrochloride with the combination of HPMC and chitosan can meet the ideal requirements for oral buccoadhesive film and a therapeutically effective amount of alfuzosin hydrochloride can be delivered via sustained release manner.

Microneedle (MN) assisted transdermal delivery is a novel technology that can overcome the stratum corneum barrier of skin and enable successful permeation enhancement of drugs. Zolmitriptan (ZT) and Rizatriptan (RT) are antimigraine drugs that show poor and variable bioavailability when administered as currently available formulations, owing to hepatic first pass metabolism. Transdermal delivery with MN application as permeation enhancement strategy was tried to efficiently delivering these molecules. For this purpose, poke and patch approach was employed. A significant enhancement in transdermal permeation of both the drugs was found with MN application. It was also found that design parameters like the MN length, needle density, etc., play a major role in such enhancement. Overall, MN application, especially via the poke and patch technique seems like a very promising technology that may hold the key to open up transdermal delivery as the major route for drug delivery in the future.

Background: Berberine (BB) is a protoberberine alkaloid with a wide spectrum of pharmacological activities considered to be a Janus kinase (Jak)2/3 inhibitor. Nevertheless, the mechanisms of berberine’s actions on joint inflammation have not been well clarified.

Aim: This study evaluated the effect of berberine on the processes of apoptosis and on the generation of senescent cells.

Methodology: The experiments were conducted in a murine model of erosive arthritis induced by intra-articular (i.a.) injection of zymosan (zymosan-induced arthritis, ZIA). Histopathologic changes were evaluated by Sudan Black B (SBB) staining. Bone marrow (BM) cell differentiation was assessed by TRAP and \(\beta\)-galactosidase staining. The apoptosis and the expression of Bcl-2 and Bax was determined by flowcytometry.

Results: Berberine decreased the generation of apoptotic and senescent cells in BM and bone, and lowered TRAIL-induced osteoclast formation. The alkaloid did not change the expression of anti-apoptotic BcL-2 and increased the expression of pro-apoptotic Bax in synovial cells. Berberine inhibited the elevation of megakaryocyte number in BM.

Conclusion: Berberine limited the accelerated generation of apoptotic and senescent cells in arthritic mice that may result in amelioration of joint inflammation.

Current medical treatments for oral infectious diseases deal with the specificity and resistance of pathogenic strains of bacteria, fungi and viruses, thus, novel substances are necessary for use as effective drugs. Plants have been a source of active chemical agents since ancient times; however, in the case of Malpighiaceae, a flowering plant family that possesses secondary metabolites that have exhibited a variety of pharmacological effects with promising results, its study still remains pendent. Since the importance of oral infections on global human health and its impact in the complications of patients with some chronic conditions, the present contribution has as objective to provide an overview of the extracts and active constituents isolated from species belonging to the Malpighiaceae family, to emphasize their activities against bacteria, fungi and viruses during recent years and their potential impact on the pathogens of the oral cavity. In the same manner, we explore the possible future development of dosage forms of potential products obtained from Malpighiaceae.

Antibacterial efficiency of the photocatalysts, TiO₂, TiO₂+CuO and WO₃+CuO, were tested against E. coli, K. pneumoniae, MRSA and P. aeruginosa under UV irradiation to irritate active oxygen from the agents. Analytic criteria were drawing bacterial growth curve, colony counting on cultivated Petri dish, measuring generation time in liquid medium, and survival rate of bacteria by Step One Plus Realtime PCR. Tungsten oxide co-doped with copper (WO₃+CuO) was the most effective in growth inhibitive activity, followed by TiO₂+CuO and TiO₂ alone. Bacteria killing potency (survival rate) of WO₃+CuO was the strongest among the agents tested, and co-doped TiO₂+CuO and TiO₂ alone were less activity than WO₃+CuO. Photocatalysts exposed bacteria took unusual behavior in growth curve at 3 hurs incubation period such as re-growth again after growth inhibition. K. pneumoniae seemed resisting to photocatalysts effect in growth, suggesting emergence of the radical oxygen resistant bacteria. More detailed analysis should be done to clarify this unacceptable phenomenon to avoid appearance of the active oxygen resistant bacteria.

Aim of the Study: This study aimed at evaluating the adverse drug effects on blood and some biochemical parameters of anti-tuberculosis drugs among patients with primary tuberculosis infection.

Study Design: Non-probability (purposive) sampling technique was employed in this study.

Place and Duration of Study: This study was carried out at the Chest Clinic unit of the Tuberculosis and Leprosy referral Hospital, Yenagoa, Bayelsa State, Nigeria. This study was conducted from July, 2017 to April, 2018.

Methodology: Tuberculosis patients were selected using standard methods for clinical diagnosis and confirmed by laboratory analysis for Mycobacterium tuberculosis using acid fast bacilli as preliminary and Gene-Xpert^® as confirmatory test. A total of 44 tuberculosis patients met the study inclusion and exclusion criteria and completed the study at the Tuberculosis and Leprosy Referral Hospital Yenegoa, Bayelsa State. Eligible patients were administered with appropriate daily dose of (rifampicin-150 mg, isoniazid-75 mg, pyrazinamide-400 mg and ethambutol-275 mg) single drug combination for two months based on bodyweight. Blood was collected and evaluated for full blood count, liver enzymes, Alkaline phosphatase (ALP), Alanine transaminase (ALT), Aspartate aminotransferase (AST); Total proteins, Bilirubin and Cholesterol at baseline, week 4 and week 8. Data were descriptively analyzed using statistical package for social sciences (SPSS 21).

Results: Treatment in the intensive therapy phase resulted in significant increase of alanine aminotransferase and alkaline phosphatase levels (P=0.5). There was also significant decrease in total cholesterol and albumin (P=0.5). The WBC was also significantly reduced (P<0.05); week 0 (12.45±1.35), week 4(8.93±0.42) and wk 8 (7.70±0.34) while the RBC was significantly raised (P<0.05); RBC: week 0 (4.02±0.12), week 4 (4.59±0.12) and week 8 (4.82±0.10). There were no significant changes in aspartate aminotransferase, total protein and total bilirubin and more so, heamatological changes were noted but not severe enough to necessitate the discontinuation of the therapy.

Conclusion: The study results showed changes in full blood count and some biochemical parameters but were not severe enough to warrant discontinuation of therapy.

TLC densitometry method for quantification of gallic acid and ellagic acid using HPTLC is developed. HPTLC is suitable method for estimation of chemical constituent present in plant material. This is the first report of quantification of these two biologically active compounds as gallic acid and ellagic acid using HPTLC from this plant. Quantification of gallic acid and ellagic acid was carried out from the methanol extract by using solvent system of Toluene: Ethyl acetate: Formic acid (6:4:0.8 v/v/v). The R_f value of Gallic acid and ellagic acid are 0.43 and 0.38 respectively. The linearity ranges of gallic acid (100 to 600 ng) and ellagic acid (100 to 600 ng) with correlation coefficient (r- values) of 0.9994 and 0.9997 respectively. The amount of gallic acid and ellagic acid was 3.01 and 11.09 µg/ml in leaf and 4.97 and 18.30 µg/ml in stem respectively. Quantification of gallic acid and ellagic acid showed good separation and resolution from other constituent of extract. The main advantage of this method is simplicity, accuracy and selectivity. Its main advantages are its simplicity, accuracy and selectivity. This method can also be used for estimation of these compounds in other herbal preparation and may be useful for standardization purposes.