Attenuation of celecoxib cardiac toxicity using Poly(δ-decalactone) based nanoemulsion via oral route.

Celecoxib (CLX), a poorly soluble anti-inflammatory drug, requires administration in higher concentrations to produce therapeutic effects, oftentimes resulting in cardiac toxicity. Therefore, in this study, we employed a nanoemulsion technology to improve the solubility of CLX using poly(δ-decalactone) (PDL) polymer as an oil and mPEG-b-PDL as a surfactant. The nanoemulsion (NE) was successfully prepared via the nanoprecipitation method. In vitro characterization was performed for size, drug release, and stability. In vivo studies were performed to establish anti-inflammatory activity, CLX induced cardiac toxicity, and pharmacokinetic profile of NE, post-oral administration. The globular size of less than 100 nm was obtained in NE with high CLX loading. The in vitro drug release studies suggested ∼90% of CLX release from NE within 96 h. A significant anti-inflammatory activity with lowered cardiac marker values was observed for CLX NE compared to a marketed drug formulation. The pharmacokinetic study revealed that the mean retention time of CLX was significantly increased with NE in contrast to the marketed formulation, suggesting the advantage of administering CLX in the form of NE owing to the higher solubility and sustained release pattern. The long-term storage stability study reveals that NE does not show significant changes in terms of size with only a slight decrement in CLX content was observed after 24 months. The obtained results indicate that CLX bioavailability has been considerably improved without being toxic to the heart with the aid of NE and advocate the use of PDL NE for developing oral formulations for poorly soluble drugs.

Targeted delivery of panitumumab-scaffold bosutinib-encapsulated polycaprolactone nanoparticles for EGFR-overexpressed colorectal cancer.

Aims: Panitumumab (anti-Erb)-conjugated polycaprolactone (PCL) nanoparticles loaded with bosutinib (BTNB) were used to develop a targeted drug-delivery system for colon cancer cells. Materials & methods: Using carbodiimide coupling, anti-Erb was conjugated to BTNB-loaded PCL nanoparticles. Dynamic light scattering, scanning electron microscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, differential scanning calorimetry, x-ray diffraction and thermogravimetric analysis were used to analyze nanoparticles. Results: According to in vitro studies, anti-Erb-BTNB-PCL nanoparticles inhibited HCT116 cells more than BTNB alone. Cell arrest at different phases was examined for apoptotic potential. An in vivo efficacy study showed that anti-Erb-BTNB-PCL nanoparticles could target tumors selectively. Conclusion: Anti-Erb-conjugated BTNB nanoparticles could specifically target colon cancer.

Synthesis and Clinical Development of Palbociclib: An Overview.

Breast cancer is the second most commonly identified cancer in women in the United States after skin cancer. The past few years have seen a substantial increase in breast cancer awareness campaigns and active research in fields of diagnosis and targeted therapy. These factors have led to a better mechanistic understanding of the disease, detection at earlier stages, and a more personalized approach to treatment, ultimately causing a crucial increase in the survival rates after detection. However, with the advances in treatment, cases of patients developing primary resistance and acquired resistance are increasing. Most of the breast cancers which develop resistance to therapy are ER+ and are typically treated with tamoxifen and fulvestrant. These drugs either lower the levels of estrogen or inhibit the receptors for estrogen and prevent the tumor from spreading. Around one-third of women treated with these drugs develop resistance to them, lowering their chances of survival. This has directed the search for newer drug therapies to target advanced breast cancer and resistance. One of these efforts has resulted in the development of Palbociclib, a first in class inhibitor of cyclin dependent kinases 4 and 6 (CDK4 and CDK6), which was granted accelerated approval from the FDA for combination therapy in postmenopausal women with ER+, HER2- metastatic breast cancer. This review is focused on the various aspects of "Palbociclib" including its synthesis, molecular modeling studies, and efficacy and safety profile with data obtained from various clinical trials.

Cissus quadrangularis L: A comprehensive multidisciplinary review.

ETHNOPHARMACOLOGICAL RELEVANCE: Cissus quadrangularis L. is a perennial herb of the Vitaceae family and is utilized comprehensively as a medicinal herb in most tropical regions by various names. This herb is documented to possess a wide-ranging ethnomedicinal uses in malaria, fever, epilepsy, gout, piles, skin diseases, colic, etc. AIM OF THE REVIEW: A organized summary of the botany, traditional uses, phytochemistry, pharmacology, toxicology, available marketed formulations and filed patents were presented to explore the future therapeutic potential and scientific potential of this herb. MATERIALS AND METHODS: For a review of the literature, various databases were searched, including PubMed, EMBASE, and Scopus etc. From, total 408 records of this herb, we have screened 155 articles consist of desired information and available as full text. Present manuscript is structured from comprehensive information on this herb from screened 155 records. Plant taxonomy was confirmed to the database "The Plant List". RESULTS: Phytochemical assessment as a whole indicated the presence of flavonoids, triterpenoids, alkaloids, saponins, iridoids, stilbenes, vitamins, steroids, and glycosides. A toxicity study revealed that its LD50 value is above 3000 mg/kg in animals indicating its safety. A variety of pharmacological studies of aerial parts of this herb by different extracts have demonstrated analgesic, anti-inflammatory, anticonvulsant, antimicrobial, anticancer, anti-osteoporotic activity and other bone-related disorders to justify its name as Hadjod. Still, the herb has been utilized in clinical practice and several patents were filed in India and US for its antiosteoporotic property. CONCLUSION: The studies on Cissus quadrangularis Linn. are extensive, but gaps still remain. The molecular mechanism, structure-activity relationship, potential synergistic and antagonistic effects of these components needs to be further elucidated. These findings suggest the need for further research on this herb for the management of several other chronic ailments.

Role of monocarboxylate transporters in head and neck squamous cell carcinoma.

Head and Neck tumors are metabolically highly altered solid tumors. Head and Neck cancer cells may utilise different metabolic pathways for energy production. Whereas, glycolysis is the major source coupled with oxidative phosphorylation in a metabolic symbiosis manner that results in the proliferation and metastasis in Head and Neck Cancer. The monocarboxylate transporters (MCTs) constitute a family of 14 members among which MCT1-4 are responsible for transporting monocarboxylates such as l-lactate and pyruvate, and ketone bodies across the plasma membrane. Additionally, MCTs mediate absorption and distribution of monocarboxylates across the cell membrane. Head and Neck cancer cells are highly glycolytic in nature and generate significant amount of lactic acid in the extracellular environment. In such condition, MCTs play a critical role in the regulation of pH, and lactate shuttle maintenance. The intracellular lactate accumulation is harmful for the cells since it drastically lowers the intracellular pH. MCTs facilitate the export of lactate out of the cell. The lactate export mediated by MCTs is crucial for the cancer cells survival. Therefore, targeting MCTs is important and could be a potential therapeutic approach to control growth of the tumor.

Human respiratory viral infections: Current status and future prospects of nanotechnology-based approaches for prophylaxis and treatment.

Respiratory viral infections are major cause of highly mortal pandemics. They are impacting socioeconomic development and healthcare system globally. These emerging deadly respiratory viruses develop newer survival strategies to live inside host cells and tricking the immune system of host. Currently, medical facilities, therapies and research -development teams of every country kneel down before novel corona virus (SARS-CoV-2) which claimed ~2,828,629 lives till date. Thus, there is urgent requirement of novel treatment strategies to combat against these emerging respiratory viral infections. Nanocarriers come under the umbrella of nanotechnology and offer numerous benefits compared to traditional dosage forms. Further, unique physicochemical properties (size, shape and surface charge) of nanocarriers provide additional advantage for targeted delivery. This review discusses in detail about the respiratory viruses, their transmission mode and cell invasion pathways, survival strategies, available therapies, and nanocarriers for the delivery of therapeutics. Further, the role of nanocarriers in the development of treatment therapy against SARS-CoV-2 is also overviewed.

Anti-inflammatory, cytotoxic and antioxidant effects of methanolic extracts of Drypetes sepiaria (Euphorbiaceae).

The aim of this study was to investigate in vitro antioxidant, anti-inflammatory and cytotoxic activities of the petroleum ether, ethyl acetate, methanol and aqueous extracts obtained from leaves of Drypetes sepiaria (Euphorbiaceae). Total phenolic and flavonoid contents of these crude extracts were determined as gallic acid and quercetin equivalents, respectively. In in vitro antioxidant method, methanol extract exhibited higher free radical scavenging activity compared to standard compound, ascorbic acid with IC50 of 95.43 µg/ml (DPPH) and 67.05 µg/ml (ABTS). Methanol extract was able to inhibit inflammation by in vitro about 85-90% (HRBC stabilization method) and in vivo about 40-45% (Paw oedema method) anti-inflammatory assays compared to standard produced 50.04% at 6 h period. In cytotoxicity assay (MTT assay) methanolic extract exhibited IC50 of 10 µg/ml. In apoptosis (flow cytometric assay), the control group showed normal caspase 3 activity in the SiHa cells which was 0.24%, and increased up to 40% after treatment.

Anticancer property of Bryophyllum pinnata (Lam.) Oken. leaf on human cervical cancer cells.

BACKGROUND: Bryophyllum pinnata (B. pinnata) is a common medicinal plant used in traditional medicine of India and of other countries for curing various infections, bowel diseases, healing wounds and other ailments. However, its anticancer properties are poorly defined. In view of broad spectrum therapeutic potential of B. pinnata we designed a study to examine anti-cancer and anti-Human Papillomavirus (HPV) activities in its leaf extracts and tried to isolate its active principle. METHODS: A chloroform extract derived from a bulk of botanically well-characterized pulverized B. pinnata leaves was separated using column chromatography with step- gradient of petroleum ether and ethyl acetate. Fractions were characterized for phyto-chemical compounds by TLC, HPTLC and NMR and Biological activity of the fractions were examined by MTT-based cell viability assay, Electrophoretic Mobility Shift Assay, Northern blotting and assay of apoptosis related proteins by immunoblotting in human cervical cancer cells. RESULTS: Results showed presence of growth inhibitory activity in the crude leaf extracts with IC50 at 552 µg/ml which resolved to fraction F4 (Petroleum Ether: Ethyl Acetate:: 50:50) and showed IC50 at 91 µg/ml. Investigations of anti-viral activity of the extract and its fraction revealed a specific anti-HPV activity on cervical cancer cells as evidenced by downregulation of constitutively active AP1 specific DNA binding activity and suppression of oncogenic c-Fos and c-Jun expression which was accompanied by inhibition of HPV18 transcription. In addition to inhibiting growth, fraction F4 strongly induced apoptosis as evidenced by an increased expression of the pro-apoptotic protein Bax, suppression of the anti-apoptotic molecules Bcl-2, and activation of caspase-3 and cleavage of PARP-1. Phytochemical analysis of fraction F4 by HPTLC and NMR indicated presence of activity that resembled Bryophyllin A. CONCLUSIONS: Our study therefore demonstrates presence of anticancer and anti-HPV an activity in B. pinnata leaves that can be further exploited as a potential anticancer, anti-HPV therapeutic for treatment of HPV infection and cervical cancer.