Current Aspects in Pharmaceutical Research and Development Vol. 6

Nowadays, nanotechnology has experienced significant growth in research and its application in the field of medicine. Nanomedicine, application of nanotechnology to medicine allows the development of nanoparticle-therapeutic carriers. Nanoparticles have shown to be vital for the delivery of poorly water-soluble drugs. Nanocarriers composed of liposomes, micelles, polymeric nanoparticles and solid lipid nanoparticles have presented tremendous opportunities in the area of drug delivery. The ‘new kid on the block’, nanostructured lipid carrier system, is now gaining currency among researchers. This is purely due to its superior properties over the other nanocarriers. In pursuit of nanostructured lipid carriers (NLCs), researchers have employed myriad of liquid and solid lipids. However, in treating diseases, the use of NLCs in ushering therapeutic agents to certain body parts has not been fully exploited.

Serpiginous Choroiditis is a rare recurrent eye disease marked by irregularly shaped (serpiginous) lesions that affect two layers of the eye surface (the retinal pigment epithelium and the choriocapillaris). Diagnosing this rare disorder is a challenge in itself followed by its complex pharmacotherapeutic approach which is seen in the following case report. It will help to bring to light the many treatment challenges in order to open a window for improved treatment regimens and early diagnosis, while keeping in mind the constant motivation and calm mind that a patient requires to combat such a rare disease.

The science of Ayurveda always suggests a holistic way of living. It strongly states that the mental status of the mother has a strong influence on foetal health. This does not start from the time of conception. Instead from the time of development of the ovum itself all the mental conditions of the mother start affecting the foetal health. In this busy urban life mental health of the mother is given less importance. Most of the women, including pregnant ladies, are under stress in the present scenario. Ayurveda very clearly explains the impact of maternal mental health on the foetus. It also suggests different consequences of its negligence and measures for maintaining the mental health of a woman during puberty, pregnancy, parturition and postnatal period. Recent studies also suggest that the thoughts and feelings of the mother will be communicated to the foetus through hormones. It can even alter the gene expression in the developing embryo. Awareness regarding the impact of the mental status of the mother on the fetus may help society to prevent the ill effects of maternal stress on the fetus. Along with the importance of nutrition and physical health care, awareness needs to be generated in society regarding the importance of maternal mental health care. This may help to reduce genetic disorders and mental health issues in the future generations.

The past several decades have seen a 'one size fits all' strategy, that is, a similar line of therapy or the use of the same drug/ medicine, that too in a conventional approach, to treat a specific ailment. This method is related to unique genetic constitutions and processes rather than specific personal attributes. Precision oncology has the potential to significantly enhance prediction, therapy, and follow-up care for patients. Identifying the numerous and diverse biological components linked with carcinogenesis has only recently been possible as a result of recent biotechnological advancements. The main objective of this chapter is to bridge the gap between the research and the clinical practice of Precision Oncology by creating awareness among the scientists, clinicians and the public as well using detailed representation of all the advances made in the field of Precision Oncology considering almost all the aspects and possibilities of the same. It also provides a comprehensive idea of the genes associated with different cancer types including the overlapping genes involved in multiple types of cancer.  Knowing a patient's genetic information and the genes sensitive to mutation can help in precise diagnosis and receive the best personalized medicines, lowering the odds of treatment failure prevalent in cancer therapy. This chapter takes into account all the aspects pf Precision Oncology and provides an overview of overlapping genes as well as genes whose mutations can lead to cancer. This assembled information could help with future clinical studies to predict and prevent cancer and academic research.

The present study was carried out to determine the Biological profile and therapeutic potentials of Cardiospermum halicacabum. Cardiospermum halicacabum is an annual or perennial herb, is commonly seen in Sri Lanka and the whole plant has been used to treat rheumatism, stiffness of limbs, and snakebites. Cardiospermum halicacabum has been used to treat Gastrointestinal problems, respiratory disorder and urinogenital infection. The leaves of Cardiospermum halicacabum contain beta-sitosterol, oxalic acid and amino acids. It has also been reported to have saponin and quebrachitol. The seed oil of the plant has erucic acid, oleic acid, eicosonic acid, octanoic acid and n-hexadecanoic acid and high concentration of triterpenoids as well.

The present study carried out to determine the Pharmacological and therapeutic potential of Cissus quadrangularis L. Cissus quadrangularis(CQ) Linn., commonly known as Veldt Grape, Winged Tree-bine or Devil’s Backbone, is a plant native to India and Sri Lanka and indigenous to Asia and Africa. Numerous studies support the development of new treatments in oncology to be added to the traditional protocols to increase the effectiveness of available treatments, reducing side effect profile, and the patients’ quality of life. Chemotherapy- induced side effects depend on various variables such as the drug employed, its dosage, and treatment duration. These side effects include pain, fatigue, throat and mouth sores, diarrhoea, nausea, vomiting, constipation, and blood disorders. Side effects affecting the nervous system are commonly experienced with chemotherapy and include cognitive dysfunction, headache, dizziness, vision loss and vision disturbances such as blurred or double vision, changes in learning and memory, sexual dysfunction, ataxia, and peripheral neuropathy

Modifying natural polymers have imparted desirable properties making them suitable as pharmaceutical additives. This work was to prepare pre-gelatinized breadfruit starch using acetone to reduce drying time and energy expended. The modified starch was evaluated as a disintegrant in paracetamol oral compacts. The mode of incorporation of disintegrants has been reported to affect their performance and the quality of tablet and its release profile. Starch from unripe mature bread fruit was pre-gelatinized, precipitated with acetone to reduce drying time. Native and pre-gelatinized starches were characterized for micromeritics, compatibility studies with test drug using Fourier Transform Infra-Red (FT-IR) and water interaction properties (viscosity, swelling power and hydration capacity). Paracetamol granules formed by wet granulation were compacted incorporating starches as disintegrant intragranularly, extragranularly and combining both methods. Disintegration and dissolution studies done. Pre-gelatinization did not alter the native starch chemically and their pH were within pharmaceutical limits. The disintegration efficiency ratio (DER) for the P2 and P3 (tablet batches with pre-gelatinized starches) compared favourably with that of corn starch. Also, the dissolution kinetics of the breadfruit starches followed the Hixson Crowel’s model while that of reference corn starch was best described by the Higuchi kinetic model. Breadfruit starch is edible and the properties of its pre-gelatinized form as a disintegrant compares favourably with corn starch BP. It could be an good alternative as pharmaceutical excipient.

In this study, we isolated fungal endophytes from Centella asiatica Linn leaves, followed by fermentation and extraction of fungal endophytes with non-polar solvents like chloroform, ethyl acetate, and n-butanol. Preliminary phytochemical analysis of endophytic crude extracts of leaves was also performed to detect the presence of primary and secondary metabolites, which was followed by an invitro free radical scavenging activity assay using reducing power, DPPH, and hydroxyl radical assays.To isolate a possible secondary metabolite, the chloroform fungal endophytic fractions were submitted to column chromatography using a gradient elution approach. With increasing concentrations, the reducing power of endophytic extracts of C. asiatica Leaf (CAL-1) (50-450\(\mu\)g/ml) increased. Reaction with DPPH radicals of CAL-1 showed good scavenging activity. The IC₅₀ values for Ascorbic acid, chloroform fraction, ethyl acetate and n- butanol fraction were found to be 30.33 \(\mu\)g /ml, 66.58 \(\mu\)g/ml, 79.33 \(\mu\)g /ml and 96.39 \(\mu\)g/ml respectively. The IC50 values for mannitol, chloroform fraction, ethyl acetate, and n-butanol fraction were found to be121.06 \(\mu\)g / ml, 141.21 \(\mu\)g/ml, 181.80 µg/ml and 189.90 \(\mu\)g/ml respectively, in the hydroxyl radical assay. Endophytic crude fractions of ethyl acetate had significantly higher antioxidant activity than other fractions. As a result, ethyl acetate fungal endophytic fractions of Centella asiatica Linn leaves have the potential to be used as an antioxidant in the prevention of oxidative stress caused by free radicals. Further investigations are needed to isolate and characterize the potential polyphenolic compounds which are present in the endophytic extracts including their mode of action in the management of oxidative stress caused by the free radicals.

Secondary metabolites of pharmaceutically importance or phytopharmaceuticals comprise alkaloids, glycosides, flavonoids, volatile oils, tannins, resins etc. At present, most of these secondary metabolites are extracted from wild or cultivated plants since their chemical synthesis is either tremendously tough or economically impracticable. Production through callus and cell suspension cultures is a gorgeous substitute, nevertheless till yet this has had only restricted marketable accomplishment owing to less-existence of empathetic of how these metabolites are synthesized. The current book chapter has summarized some of the current progresses and investigations conducted by authors for the production of some of the useful bioactive secondary metabolites viz., withanolides, bacosides, glychyrhizin, reserpine, ajmalicine, amarogentin, plumbagin and terpenoids from callus and cell suspension cultures of corresponding plant species. The similar have been deliberated vastly.

Aim: Silymarin, a complex polyphenolic component mixture with anti-oxidant, anti-inflammatory, and membrane-stabilizing property is being investigated in several dermatological conditions. Present research aims to evaluate potential of silymarin loaded nanocochleates and liposomal topical application for treating chronic skin diseases.

Objectives: present study was carried out with the objectives to prepare and evaluate Silymarin loaded liposomes and optimize the same. Conversion of these liposomes into nanocochleates for improved efficacy in terms of drug entrapment, antimicrobial activity, cytotoxicity to HaCaT cell lines and short term stability studies.

Study Design: Silymarin loaded liposomes and nanocochleates were formulated and optimized using Design Expert software. Different invitro and exvivo tests were performed to compare their performance.

Methodology: Liposomes were prepared using ethanol injection method and further treated with calcium chloride to form nanocochleates by trapping method. Design of experiments (3² Factorial Design) was used for optimization of nanocochleates. Cell line studies (HaCaT cell lines) and short term stability studies were performed to compare the efficacy and stability respectively.

Results: Particle size, entrapment efficiency and drug deposition in Wistar Rat Skin was found to be statistically significant for nanocochleates over liposomes proving superiority of cochleates. Both the carriers sustained release of silymarin for 24h. Antimicrobial efficacy of nanocochleates against E.coli and S.aureus was significant. Inhibition of hyper proliferation of HaCaT cell lines (key mechanism by which most of the antipsoriatic drugs act) demonstrated the superiority of nanocochleates over liposomes. Nanocochleates also displayed better stability compared to liposomes due to decreased entrapment efficacy and leakage of drug.

Conclusion: Silymarin loaded Nanocochleates could prove as a promising topical drug delivery system for the treatment of chronic skin diseases like psoriasis.

The purpose of this study was to look into the hepatoprotective potential of Dyschoriste littoralis Nees (family Acanthaceae) on paracetamol-induced hepatotoxicity in rats. The aerial parts of Dyschoriste littoralis Nees. powder was extracted with various solvents (PE, EA and methanol) through Soxhlet extractor and crude various extracts utilized for hepatoprotective activity. The acute toxicity study was found that all the extracts are safe up to 2000mg/kg, so one tenth of this dose was consider as evaluation dose. Different extracts (Petroleum ether, Ethyl acetate and Methanol) of Dyschoriste littoralis were administered in dose of 200mg/kg/day to rats fed with high fat diet to assess its possible lipid-lowering potential Hepatotoxicity was induced by paracetamol (2g/kg b.wt.) on the 5^th day of the investigational period and given orally. The activities of liver enzymes such as SGOT, SGPT, ALP, gamma-glutamyl transpeptidase (GGT), creatinine, urea, total bilirubin, total cholesterol, and triglyc in the serum of paracetamol-induced rats were enhanced. Additionally, when compared to other extracts, oral administration of the ethyl acetate extract of Dyschoriste littoralis (200 mg/ kgb.wt.) given rats significantly reduced the level of SGOT, SGPT, ALP, gamma-glutamyltranspeptidase (GGT), creatinine, urea, total bilirubin, total cholesterol & triglycerides and significantly increased the concentration of total protein and albumin. The findings suggested that the ethyl acetate extract of Dyschoriste littoralis could provide better hepatoprotective activity in rats exposed to paracetamol-induced hepatotoxicity.

Background: Adverse gastrointestinal events are the commonest unwanted effects of the NSAIDs, and are believed to result mainly from the inhibition of gastric COX-1, which is responsible for the synthesis of prostaglandins that normally inhibit acid secretion and protect the mucosa. Previous studies report, that selective COX-2 inhibitors are safer when compared to non-selective cyclooxygenase inhibitors, regarding their adverse effects on gastrointestinal system. But, recent studies reveal, that gastrointestinal safety of these selective COX-2 inhibitors is not much better than that of conventional NSAIDs.

Aims: In view of the wider usage of selective COX-2 inhibitors, the study has been taken up to report, whether selective COX-2 inhibitors have got any advantages over conventional NSAIDs or not, in regard to their gastrointestinal side effects.

Methods: Patients were divided into eight groups, fifteen patients of each. Each group was given one of the NSAIDs from the eight drugs those were selected for the study, for 15 days. In the selected group, along with the symptomatic assessment of gastric toxicity, both pre and post-treatment values of Hb% are estimated, tabulated & subjected to statistical analysis.

Results: Both the drugs; diclofenac & meloxicam have shown significant changes in the Hb% values (‘p’ value 0.02 each), whereas selective COX-2 inhibitors like nimesulide & celecoxib were no less in gastric toxicity, in comparison with diclofenac; on symptomatic assessment. Diclofenac and meloxicam have shown significant change in the ‘p’ value, in the assessment of Hb% change both before and after treatment, showing that there must have been gastric bleeding erosions which must have given rise to such changes and thus to anemia, without any alarming symptoms.

Conclusions: In our short-term study, selective COX-2 inhibitors did not show any advantage over non-selective NSAIDs regarding their gastrointestinal toxicity.

In present work isolation and characterisation of a chalcone [(E)-3-(3,4-dihydroxyphenyl)-1-(2,3,4-trihydroxyphenyl) prop-2-en-1-one] or okanin has been described. The isolation was based on bio-assay guided fractionation. The methanol, hexane extracts and isolated okanin from methanol extracts were exhibited good antibacterial activity towards various pathogens gram positive (Micrococcus luteus and Staphlcocous aureus) and gram negative bacteria (Escherichia coli, R. planticola and Acinetobacter). The anti-inflammatory activity of hexane extracts, methanol extracts of Dalbergia sisso Roxb and okanin have been studied. The methanolic extract showed maximum activity. Dried leaves of Dalbergia sissoo is exhibited antibacterial, antiprotozoal, anti-inflammatory activity. This is the first report of any chalcone from the genus Dalbergia. The finding suggests more research would be required for presence of new phytoconstituents.