MULTI-FUNCTIONAL CARBON DOTS: A SYSTEMATIC OVERVIEW

Carbon dots (CDs) have emerged as a potential material in the multifarious fields of biomedical applications due to their numerous advantageous properties including tunable fluorescence, water solubility, biocompatibility, low toxicity, small size and ease of modification, inexpensive scale-up production, and versatile conjugation with other targeted nanoparticles. Thus, CDs became a preferable choice in various biomedical applications such as nanocarriers for drugs, therapeutic genes, photo sensitizers, unique electronic, fluorescent, photo luminescent, chemiluminescent, and electro chemiluminescent, drug/gene delivery and optoelectronics properties are what gives them potential in sensing and antibacterial molecules. Further, their potentials have also been verified in multifunctional diagnostic platforms, cellular and bacterial bio-imaging, development of nanomedicine, etc. This present review provides a concise insight into the progress and evolution in the field of carbon dots research with respect to synthesis methods and materials available in bio-imaging, theranostic, cancer, gene therapy, diagnostics, etc. Further, our discussion is extended to explore the role of CDs in nanomedicine and nano theranostic, biotherapy which is the future of biomedicine and also serves to discuss the various properties of carbon dots which allow chemotherapy and gene therapy to be safer and more target-specific, resulting in the reduction of side effects experienced by patients and also the overall increase in patient compliance and quality of life and representative studies on their activities against bacteria, fungi, and viruses reviewed and discussed. This study will thus help biomedical researchers in percuss the potential of CDs to overcome various existing technological challenges

Combinational effect of angiotensin receptor blocker and folic acid therapy on uric acid and creatinine level in hyperhomocysteinemia-associated hypertension

© 2019 International Union of Biochemistry and Molecular Biology, Inc. Homocysteine [HSCH2CH2CH(NH2)COOH] (Hcy) is a sulfur-containing amino acid of 135.18 Da of molecular weight, generated during conversion of methionine to cysteine. If there is a higher accumulation of Hcy in the blood, that is usually above 15 µmol/L, it leads to a condition referred to as hyperhomocysteinemia. A meta-analysis of observational study suggested an elevated concentration of Hcy in blood, which is termed as the risk factors leading to ischemic heart disease and stroke. Further experimental studies stated that Hcy can lead to an increase in the proliferation of vascular smooth muscle cells and functional impairment of endothelial cells. The analyses confirmed some of the predictors for Hcy presence, such as serum uric acid (UA), systolic blood pressure, and hematocrit. However, angiotensin-converting enzyme inhibitors angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) alone are inadequate for controlling UA and creatinine level, although the addition of folic acid may be beneficial in hypertensive patients who are known to have a high prevalence of elevated Hcy. We hypothesized that combination therapy with an ARB (olmesartan) and folic acid is a promising treatment for lowering the UA and creatinine level in hyperhomocysteinemia-associated hypertension

A COMPREHENSIVE REVIEW ON SUPERSATURABLE SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM

Lipid-based drug delivery systems are extensively reported in the literature for enhancing drug solubility, permeability, and bioavailability. Self-nanoemulsifying drug delivery systems (SNEDDS) are a superior strategy for enhancing solubility and bioavailability of poorly water-soluble compounds and the most prevailing and commercially viable oil-based approach for drugs that exhibit low dissolution rate and inadequate absorption. However, these formulations have few limitations that include in vivo drug precipitation, inferior in vitro in vivo correlation owing to unavailability of in vitro tests, handling issues of liquid formulation, and physicochemical instability of drugs. These limitations are overcome by potential systems such as supersaturable SNEDDS (S-SNEDDS) which are prepared by addition of precipitation inhibitors into formulated SNEDDS to maintain drug supersaturation post dispersion in gastrointestinal tract. These systems improve drug bioavailability and reduce the inconsistency of exposure. In addition, these formulations also help to overcome the drawbacks of liquid and capsule dosage forms. The S-SNEDDS provides an effective approach for improving the dissolution and bioavailability of anti-cancer agents. In this article, an attempt was made to present an overview of SNEDDS, S-SNEDDS, their mechanism, formulation excipients, recent advancements, advantages, and disadvantages of SNEDDS formulations. The article also focuses on reviewing the application of S-SNEDDS in enhancing the solubility and bioavailability of anti-cancer drugs in cancer therapy

A SYSTEMATIC REVIEW ON SUPERSATURABLE SELF-NANO EMULSIFYING DRUG DELIVERY SYSTEM: A POTENTIAL STRATEGY FOR DRUGS WITH POOR ORAL BIOAVAILABILITY

The most fundamental important extensive constitutive of drug molecules to be available for systemic absorption is aqueous solubility; subsequently, that is the nature of GIT fluid. When the drug molecules become solubilized, it has to reach the systemic circulation via the biological membrane. The solubility problem of many effective pharmaceutical molecules is still one of the major challenges in the formulation of this molecule. Drug molecules that belong to class II have a problem in bioavailability mainly due to low aqueous solubility and the rate-limiting step is the dissolution process and so electing of suitable drug delivery and proper additives are decisive to overcome this major obstruction and promote the fraction that will reach the systemic circulation. Among the different lipid-based systems, the su-SNEDDSs have gained attention because the inclusion of precipitation inhibitors within su-SNEDDSs helps maintain drug supersaturation after dispersion and digestion in the gastrointestinal tract. This enhances the bioavailability of drugs and minimizes the variability of exposure. Nowadays, supersaturable self-nano emulsifying and nano lipid-based drug delivery systems have constrained a substantial concern from pharmaceutical scientists for managing the oral delivery of poorly water-soluble compounds. By following oral administration, self-nano emulsifying drug delivery systems show complex aqueous dispersion and digestion in the GIT and enduring intestinal lymphatic transport, exorbitant pre-absorptive metabolism by gut membrane-bound cytochrome enzymes and preventing P-gp mediated drug efflux. Mostly these processes result in drug supersaturation, which leads to increased absorption or the high drug concentrations may cause precipitation with capricious and variable oral bioavailability. This procession review briefly summarized drug supersaturation obtained from self-nano emulsifying and other lipid-based formulations and this review also delineate the effects of numerous physiological factors and the probable interactions between PIs and lipid, lipase or lipid digested products on the in vivo performance of su-SNEDDS and focuses on reviewing the application of su-SNEDDS in enhancing the solubility and bioavailability of anti-cancer drugs in cancer therapy

FORMULATION AND IN VIVO EVALUATION OFPEMIGATINIB SUPERSATURABLE SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM

Objective: Pemigatinib is an active component in treatment of cholangiocarcinoma, but the low solubility and bioavailability of Pemigatinib limit its wide application. The aim of the present study was to prepare and evaluate supersaturable self-nanoemulsifying drug delivery systems (sSNEDDS) followed by investigating and comparing the pharmacokinetic profiles of Pemigatinib and Pemigatinib sSNEDDS in rat plasma by HPLC. Methods: Pemigatinib loaded SNEDDS were obtained by dissolving drug in the isotropic mixture of oil, surfactant, and co-surfactant. The conventional SNEDDS were converted to sSNEDDS by precipitation method by using experimented polymer. An appropriate high sensitivity and selectivity was applied to the comparison of plasma pharmacokinetics in Pemigatinib and Pemigatinib sSNEDDS using Entrectinib as internal standard (IS). Results: The droplet of sSNEDDS ranges from 166.78 ± 3.14 to 178.86 ± 1.24 nm with PDI 0.212 – 0.256, transmission electron microscopy images revealed the spherical shape of the nanodroplets, emulsification time was 15 secs when added to physiological fluids, percent transmittance of the diluted formulation was 99.12 ± 0.46, and viscosity was 574 ± 26 centipoises indicating the good flow ability. FTIR and DSC studies indicated the amorphization of the drug. The dissolution profile of sSNEDDS indicated the faster release of drug compared to both pure drug suspension and SNEDDS formulation. Cmax of the sSNEDDS 3.52±0.13ng/mL was significant (P< 0.05) as compared to the pure drug suspension formulation 2.82±0.42 ng/mL. The AUC0-t, AUC0–∞ of sSNEDDS was increased, while the Tmax and t1/2 was decreased. Moreover, the AUC value in the sSNEDDS group was significantly increased and the relative bioavailability was calculated to be 69% when compared with that of the Pemigatinib group. Conclusion: These results concluded that Pemigatinib sSNEDDS when compared with pure drug after a single oral administration and the formulation modification of Pemigatinib into sSNEDDS can effectively enhance gastrointestinal absorption and relative bioavailability by improving solubility and dissolution rate

Acute and sub-acute toxicity studies of hydroalcoholic extract from Acacia suma (Roxb) (Fabaceae) stem barks

Herbal medicines are popular remedies for diseases used by a vast majority of the world’s population. The pharmacological effects of many plants have been studied in various laboratories, whereas there are many limitations regarding the safety and efficacy. Our research group has previously investigated the phytochemical and pharmacological properties of this plant. The present study was carried out to evaluated acute and subacute toxicity of hydroalcoholic extract from stem bark of Acacia suma (Roxb.) var. Acacia polyacantha (Family- Fabaceae). Acute toxicity study was evaluated on male Swiss albino mice (20-25g) and Wistar albino rats (150-200g) were assigned for sub-acute toxicity, after ingestions of the extract during one day (acute model) and during 15 days (subacute model). The acute toxicity studies were conducted as per the OECD guidelines 423, where the limit test dose of 3000 mg/kg b.wt., p.o., used. Results showed that the LD50 of the extract is higher than 3000 mg/kg b.wt., and there was no mortality was observed at 3000 mg/kg b.wt., p.o., dose except with prominent diuresis and purgation, these toxic sign are probably due to the saponins content of the extract; so, testing of the hydroalcoholic extract of Acacia suma stem bark at higher dose was practically non-toxic. In sub-acute toxicity study, the extract treated groups (300 and 600 mg/kg b.wt., p.o.) did not show any significant changes in body weight when compared to the control group. The weight of the liver, kidney and pancreas were found to be unaltered in the experimental groups compared with the control group. The haematological and biochemical parameters (hepatic and renal function tests) did not show any significant changes in the sample treated groups when compared with the control group animals

Acute and sub-acute toxicity studies of hydroalcoholic extract from Acacia suma (Roxb) (Fabaceae) stem barks

Herbal medicines are popular remedies for diseases used by a vast majority of the world’s population. The pharmacological effects of many plants have been studied in various laboratories, whereas there are many limitations regarding the safety and efficacy. Our research group has previously investigated the phytochemical and pharmacological properties of this plant. The present study was carried out to evaluated acute and subacute toxicity of hydroalcoholic extract from stem bark of Acacia suma (Roxb.) var. Acacia polyacantha (Family- Fabaceae). Acute toxicity study was evaluated on male Swiss albino mice (20-25g) and Wistar albino rats (150-200g) were assigned for sub-acute toxicity, after ingestions of the extract during one day (acute model) and during 15 days (subacute model). The acute toxicity studies were conducted as per the OECD guidelines 423, where the limit test dose of 3000 mg/kg b.wt., p.o., used. Results showed that the LD50 of the extract is higher than 3000 mg/kg b.wt., and there was no mortality was observed at 3000 mg/kg b.wt., p.o., dose except with prominent diuresis and purgation, these toxic sign are probably due to the saponins content of the extract; so, testing of the hydroalcoholic extract of Acacia suma stem bark at higher dose was practically non-toxic. In sub-acute toxicity study, the extract treated groups (300 and 600 mg/kg b.wt., p.o.) did not show any significant changes in body weight when compared to the control group. The weight of the liver, kidney and pancreas were found to be unaltered in the experimental groups compared with the control group. The haematological and biochemical parameters (hepatic and renal function tests) did not show any significant changes in the sample treated groups when compared with the control group animals

APTAMERS: NANOMATERIALS AS A POTENTIAL AGENT FOR ANTIVIRAL THERAPEUTIC DRUG DELIVERY DEVELOPMENT: A SYSTEMATIC LITERATURE REVIEW

Chemotherapeutic experts have been utilised to cure a variety of disorders, but their practical application is restricted due to their regrettable selectivity and outrageous fundamental optional effects. Short single-stranded DNA or RNA oligonucleotides known as aptamers are released from randomised libraries and have strong propensity and differentiation towards targets like antibodies as well as characterised structures and ties to targets like proteins. They commonly suppress protein interactions while restricting proteins, which may elicit positive effects like threat. Aptamers have recently demonstrated their amazing promise for use in medicines, biosensors, and bioimaging thanks to a number of advantages, such as minimal immunogenicity, simplicity of giant degree blend, low pack to-bunch collection, genuinely substance modification, and programmability.  At any rate, the steady for the most part accomplishment speed of aptamer is far from being brilliant, despite everything needs to overwhelm the gigantic obstruction in propensity, constancy for utilitarian application, explicit illness cell affirmation. The sensible method of controlling the binding execution of aptamers, and dealing with their show in the practical application is of great significance and these single-abandoned DNA or RNA aptamers could outline with astoundingly poisonous chemotherapy drugs, hurts, strong RNAs or different particles as novel aptamer-drug structures, which are prepared to do endlessly out working on the obliging plentifulness and decreasing the critical danger of solutions and have unprecedented possible in living spaces for appointed ailment treatment. In this survey, we have extensively covered and summarised the ongoing improvements in the aptamer-drug structure philosophy for designated drug transport in the assessment methodologies of aptamers for unambiguous disease biomarkers. A modified strategy utilising aptamers could be a reliable system for quick and precise advancement of biopharmaceutics for use in infection-related treatment, especially in light of the enormous advances in modernised thinking for protein and RNA structure conjectures. Additionally, the likelihood of future conception is also summarised

Combined green analytical principles and quality by design for ultraperformance liquid chromatography analytical method development, the characterization and in-silico toxicity prediction of Ixazomib degradation products using mass spectrometry

Ixazomib citrate (IC) is the first oral selective proteosome inhibitor for treating multiple myeloma. IC is prone to degradation due to its oxidative deboronation and the amide bond, affecting patient health, drug quality, and efficacy. The stability of IC is crucial during drug development as it guides the inherent stability of the molecule, its degradation pathways, packing materials, and formulation development. Following the International Conference on Harmonization (ICH) Q1A (R2) and Q1B, a stability study were performed for both solution and solid-state stress studies. Under oxidative and alkaline conditions, 3 degradation products (DPs) were identified, separated, and method-validated according to ICH Q2 (R1) guidelines. From the Design Expert statistical tool, the Central Composite Design was used to optimize the final analytical method conditions, where the p-values for the model are < 0.05%. Green analytical chemistry has significantly reduced the use of hazardous organic solvents without losing chromatographic performance. The green separation and quantification of DPs and IC on Ultra Performance Liquid Chromatography (UPLC) using an Inert-Sustain C8 (50×3.0) mm 2.0 µm column with gradient elution using 10 mM ammonium acetate buffer (pH 5.0) and ethanol at a flow rate of 0.5 mL/min and detection at 230 nm. The results of green assessment tools like GAPI, AGREE, and Analytical eco-scale found that the method is excellent for the greenness of utilizing ethanol as a solvent, shorter runtime, and lesser waste. The method was validated as per ICH Q2 guidelines, and the results found it is sensitive, precise, accurate, robust, and linear for its intended use. The method is suitable for quantifying IC and its DPs from 2.0 to 150 µg/mL with R2 values of 0.9996 with a detection limit of 1.0 µg/mL. The plausible degradation structures and pathways of DPs were outlined using tandem mass spectra employed on LC-QTOF-MS/MS in both ESI positive and negative modes. The mechanistic explanation for establishing DPs was explained in detail. The ADMET Predictor™ software predicted the physicochemical and ADMET properties. The toxicity profile reveals that DP2 and DP3 are teratogenic, while D1 and D3 show phospholipidosis