Search

Abstract: Preterm birth (PTB) (< 37 completed weeks gestation) is a pathological outcome of pregnancy and its associated complications are the leading global cause of death in children younger than 5 years of age. Babies born prematurely have an elevated risk for short- and long-term adverse effects of medical and neurodevelopmental sequelae. Substantial evidence suggests that multiple sets of symptoms are allied with PTB etiology, and the exact mechanism cannot be recognized. Notably, various proteins, especially (i) complement cascade; (ii) immune system; and (iii) clotting cascade, have become attractive research targets that are associated with PTB. Further, a small imbalance of these proteins in maternal or foetal circulation could serve as a marker/precursor in a series of events that lead to PTBs. Thus, the present review lightens the basic description of the circulating proteins, their role in PTB, and current concepts for future development. Further, deepening the research on these proteins will lead to a better understanding of PTB etiology and alleviate scientists' confidence in the early identification of PTB mechanisms and biological markers.

Abstract: MicroRNAs (MiRNAs) are endogenous non-coding small RNA molecules that regulate gene expression in plants, animals and some viruses. Both normal and pathological liver processes are regulated by miRNAs. Recent research indicated that miRNAs have been implicated in liver diseases caused by viral hepatitis (Hepatitis B and Hepatitis C), metabolic problems, alcohol and drug abuse. Because altered miRNA expression is linked to liver metabolic dysregulation, liver damage, liver fibrosis, and tumour growth, miRNAs are promising therapeutic targets for the detection and treatment of liver diseases. In this review, we summarise the current knowledge about the role of microRNAs in acute and chronic liver diseases, including hepatocellular carcinoma. We cover the miRNA-based therapy for liver disorders as well as the use of miRNAs as biomarkers for early diagnosis, prognosis and assessment of liver diseases. The investigation of miRNAs in liver diseases will provide a better understanding of the pathogeneses, identification of biomarkers and therapeutic targets for liver diseases in the future.

7-Methylxanthine (7-MX, CAS No. 552-62-5, purity 99.46%) is the first orally administered drug candidate, which showed anti-myopic activity in different pre-clinical studies. In the present study, we investigated the

Overexpression of Cytochrome P450 1B1 in malignancies is accountable for the biotransformation-based inactivation of various chemotherapeutics such as docetaxel, paclitaxel, cisplatin, and tamoxifen. Additionally, it also plays a major role...

Cytochrome P4501B1 (CYP1B1) is reported to be overexpressed in various malignancies including ovarian, lung, lymph, and breast cancers. The overexpression of this enzyme is accountable for the biotransformation-based inactivation of some anti-cancer drugs i.e. Docetaxel, Paclitaxel, and Cisplatin. To circumvent solutions to this issue, the current study reports some optimized derivatives of benzochalcone as selective CYP1B1 inhibitors. The optimized derivatives were screened using some structure-based drug-designing approaches including molecular docking and molecular dynamics. The implemented approaches revealed that all the designed molecules demonstrated not only essential interactions with key amino acid residues but also maintained stability within the active site of CYP1B1. Furthermore, to validate the in-silico results and develop a SAR, the designed molecules were subsequently synthesized and tested for their ability to selectively inhibit CYP1B1 over CYP1A1 using well established EROD assay. This assay results suggested that compounds 1(c), 1(d), and 1(e) are eightfold more selective CYP1B1 inhibitors over CYP1A1 with IC

Hyaluronic Acid (HA) has been applied as an anti-ageing molecule in the form of topical products. Current topical commercial formulations of HA face the limitations of very small and stagnant skin permeation, thereby demanding enduring administration of the formulation to sustain its action. In this study, Lipid-based nanocarriers in the form of ethosomes were formulated in a 1% w/w HA strength and were extensively evaluated

Drug-metabolizing enzyme (DME)-mediated pharmacokinetic resistance of some clinically approved anticancer agents is one of the main reasons for cancer treatment failure. In particular, some commonly used anticancer medicines, including docetaxel, tamoxifen, imatinib, cisplatin, and paclitaxel, are inactivated by CYP1B1. Currently, no approved drugs are available to treat this CYP1B1-mediated inactivation, making the pharmaceutical industries strive to discover new anticancer agents. Because of the extreme complexity and high risk in drug discovery and development, it is worthwhile to come up with a drug repurposing strategy that may solve the resistance problem of existing chemotherapeutics. Therefore, in the current study, a drug repurposing strategy was implemented to find the possible CYP1B1 inhibitors using machine learning (ML) and structure-based virtual screening (SB-VS) approaches. Initially, three different ML models were developed such as support vector machines (SVMs), random forest (RF), and artificial neural network (ANN); subsequently, the best-selected ML model was employed for virtual screening of the selleckchem database to identify potential CYP1B1 inhibitors. The inhibition potency of the obtained hits was judged by analyzing the crucial active site amino acid interactions against CYP1B1. After a thorough assessment of docking scores, binding affinities, as well as binding modes, four compounds were selected and further subjected to

Acute liver damage (ALD) can cause biochemical and pathological changes, which can lead to major complications and even death. The goal of the study was to examine the therapeutic efficacy of liposomes of Bergenia ciliata extract against thioacetamide-induced liver damage in rats. Liposomal batches of B. ciliata extract were prepared by altering the kind and amount of phospholipids and characterized through various physiochemical properties such as laser diffraction, TEM, encapsulation efficiency, stability and in-vitro release studies. In-vivo hepatoprotective studies were performed on TAA-induced acute hepatic damage model. Further, in-silico studies of bergenin against the three hepatic damage markers viz. TGF-β1, TNF-α and interleukin-6 were also performed. Laser diffraction and TEM showed that most stable liposome batch of B. ciliata extract were in the range of 678-1170 nm with encapsulation efficiency of 84.3±3.5. Extract was found to be rapidly dissociated from B. ciliata liposomes in HCl than PBS, according to in-vitro release data. In-vivo data revealed a significant decline in LFT indicators, amelioration of pathological changes and high bergenin bioavailability in the liposomal group. Protective activity of bergenin against ALD targets like TGF-β1, TNF-α and interleukin-6 was anticipated via molecular docking research. As a result, the current findings of the study indicate that B. ciliata liposomes and bergenin have promising ameliorative potential in the management of ALD.

The present study aims to develop carboplatin injectable microspheres using spray-drying technology. The optimized powdered microspheres (MS-19-ST2) were morphologically spherical, with a 1.795 μm particle size and good micromeritic properties. Under normal temperature conditions, the MS-19-ST2 formulation exhibited a sustained release behaviour following first-order drug release kinetics with no compatibility issues with aluminium syringes. Furthermore, MS-19-ST2 formulation outperformed its commercial counterpart in terms of in vivo pharmaco-kinetics and -dynamics (MRT-13.9 ± 0.9 h, T

Abstract: More than 150 million people have significant fungal diseases that greatly impact health care and economic expenditures. The expansion of systemic fungal infections and invasive mycoses is being driven by an increase in the number of immunocompromised patients and the recent COVID-19 patients, especially severely ill. There have been numerous cases of fungal infections linked to COVID-19, with pulmonary aspergillosis dominating at first but with the subsequent ap-pearance of mucormycosis, candidiasis, and endemic mycoses. Candida spp. is the most frequent pathogen, with approximately 1 billion infections yearly, among other species causing the most prevalent invasive fungal infections. The importance of recognizing the epidemiological shifts of invasive fungal infections in patient care cannot be overstated. Despite the enormous antifungal therapies available, these infections are difficult to diagnose and cause high morbidity and mortality rates. Treatment choices for systemic fungal infections are severely limited due to the limitations of conventional therapy effectiveness and drug toxicities. So the researchers are still looking for novel therapeutic options, such as carrier-based approaches that are convenient and cost-effective with high and long-lasting fungal infection cure rates with reduced toxicities. The focus of this study is on summarizing the nanotechnology, immunotherapy methods and the drugs under clinical trials that have been employed in treatment as carrier-based antifungal formulations. Most of these have been reported to be promising strategies with broad-spectrum antifungal action and the potential to overcome antibiotic resistance mechanisms. We speculate that this review summarized the current knowledge to its best that will help the future developments of new antifungal therapies.

Docetaxel (DTX) is a highly lipophilic, BCS class IV drug with poor aqueous solubility (12.7 µg/mL). Presently, only injectable formulation is available in the market which uses a large amount of surfactant (Tween 80) and dehydrated alcohol as a solubilizer. High concentrations of Tween 80 in injectable formulations are associated with severe consequences i.e. nephrotoxicity, fluid retention, and hypersensitivity reactions. The present study aims to eliminate Tween 80, thus novel biocompatible surfactant Vitamin E TPGS based nanovesicle formulation of DTX (20 mg/mL) was developed and evaluated for different quality control parameters. Optimized nanovesicular formulation (NV-TPGS-3) showed nanometric size (102.9 ± 2.9 nm), spherical vesicular shape, high drug encapsulation efficiency (95.2 ± 0.5%), sustained-release profile and high dilution integrity with normal saline.

Myopia (nearsightedness) is a vision disorder with a blurring of far objects, affect millions worldwide. 7-methylxanthine (7-MX) is a molecule that is presently under clinical investigation for the treatment of myopia. In the present study, we have investigated sub-chronic and chronic toxicity of 7-MX in comparison to other clinically used methylxanthines i.e., caffeine and theobromine as per OECD guidelines 408 and 452. 7-MX was administered orally for 90 days at three different doses of 250, 500, and 1000 mg/kg for sub-chronic toxicity evaluation, and at a limit dose of 1000 mg/kg in 180 days chronic toxicity evaluation in rats. In sub-chronic treatment, 7-MX showed no mortality and signs for toxicity in any group, whereas 10% and 40% mortality with signs for toxicity were observed in caffeine and theobromine treated groups, respectively. A similar, safety profile was observed with 7-MX in 180 days of chronic toxicity study. Further, to confirm any morphological changes in organs; ultrasound and X-rays analysis were performed and no changes in the size of organs, cyst formation, fluid retention, or crystal formation was observed. Thus, the repeated dose study of 7-MX for 180 days may augment the possibility of using 7-MX clinically for the safe and effective treatment of myopia.

Locoregional drug delivery is a novel approach for the effective delivery of anti-cancer agents as it exposes the tumors to high concentration of drugs. In situ gelling systems have fetched paramount attention in the field of localized cancer chemotherapy due to their targeted delivery, ease of preparation, prolonged or sustained drug release and improved patient compliance. Numerous polymers have been investigated for their properties like swelling along with biodegradation, drug release and physicochemical properties for successful targeting of the drugs at the site of implantation. The polymers such as chitosan, Hyaluronic Acid (HA), poloxamer, Poly Glycolic Lactic Acid (PGLA) and Poly Lactic Acid (PLA) tend to form in situ hydrogels and have been exploited to develop localized delivery vehicles. These formulations are administered in the solution form and on exposure to physiological environment such as temperature, pH or ionic composition they undergo phase conversion into a hydrogel drug depot. The use of in situ gelling approach has provided prospects to increase overall survival and life quality of cancer patient by enhancing the bioavailability of drug to the site of tumor by minimizing the exposure to normal cells and alleviating systemic side effects. Because of its favorable safety profile and clinical benefits, United States Food and Drug Administration (U.S. FDA) has approved polymer based in situ systems for prolonged locoregional activity. This article discusses the rationale for developing in situ systems for targeted delivery of anti-cancer agents with special emphasis on types of polymers used to formulate the in situ system. In situ formulations for locoregional anti-cancer drug delivery that are marketed and are under clinical trials have also been discussed in detail in this article.

Xanthan gum (XG)-based hydrogels containing sodium hydroxide (NaOH) salt were synthesized with the use of distilled water (DW) at room temperature and characterized through FTIR, TGA/DTG, and rheological studies. Sodium hydroxide is used to control pH toward neutral region along with improvement in ionic conductivity and stability of the electrolyte. The stabilized hydrogel has been obtained by applying heat treatment at ambient temperature for 5 wt% XG in 0.015 M solution of NaOH, which exhibits nearly neutral pH value at room temperature. The modification/shifting of the various peaks in FTIR spectra of xanthan gum with the addition of salt indicates the interaction or cross-linking between the constituents (xanthan gum, distilled water, and NaOH) and disappearing of peaks after heat treatment of the gel confirms its stability. DTG and TGA studies have been carried out to investigate thermal stability of these gels and illustrate the effect of heat treatment as a result of salt addition with thermogravimetric analysis up to 400 °C. However, rheological studies were performed for these hydrogels to analyze their viscosity behavior and mechanical stability. Along with the above characterization, gel sample (5 wt% XG in 0.015 M NaOH solution in DW) exhibits high ionic conductivity of 4.71 × 10−3 S/cm with 6.45 pH value at room temperature after heat treatment. These highly ion conducting, thermally and mechanically stable biodegradable xanthan gum-based hydrogels can also be used as an electrolyte for various device applications like supercapacitors, fuel cells, solar cells, etc.

Development of self-nanoemulsifying drug delivery systems (SNEDDS) of docosahexaenoic acid (DHA) is reported with the aim to achieve enhanced dissolution rate. The optimized composition of liquid SNEDDS (L-SNEDDS) formulation was Labrafil M1944 CS, 47% v/v Tween 80, 27% v/v Transcutol P, and 0.1% v/v DHA. L-SNEDDS were solidified using Syloid XDP 3150 as solid porous carrier. The droplet size, polydispersity index, zeta potential, percentage drug loading, and cloud point for L-SNEDDS were found to be 43.51 ± 1.36 nm, 0.186 ± 0.053, -19.20 ± 1.21 mV, 93.23 ± 1.71, and 88.60 ± 2.54 °C, respectively. Similarly, for solid SNEDDS (S-SNEDDS) the above parameters were found to be 57.32 ± 1.87 nm, 0.261 ± 0.043, -16.60 ± 2.18 mV, 91.23 ± 1.88, and 89.50 ± 1.18 °C, respectively. The formulations (L-SNEDDS, S-SNEDDS powder, and S-SNEDDS tablet) showed significant (

The role of mushroom polysaccharides and probiotics as pharmaceutical excipients for development of nanocarriers has never been explored. In the present study an attempt has been made to explore Ganoderma lucidum extract powder (GLEP) containing polysaccharides and probiotics to convert liquid self nanoemulsifying drug delivery system (SNEDDS) into solid free flowing powder. Two lipophilic drugs, curcumin and quercetin were used in this study due to their dissolution rate limited oral bioavailability and poor permeability. These were loaded into liquid SNEDDS by dissolving them into isotropic mixture of Labrafill M1944CS, Capmul MCM, Tween-80 and Transcutol P. The liquid SNEDDS were solidified using probiotics and mushroom polysaccharides as carriers and Aerosil-200 as coating agent. The solidification was carried out using spray drying process. The process and formulation variables for spray drying process of liquid SNEDDS were optimized using Box Behnken Design to attain required powder properties. The release of both drugs from the optimized spray dried (SD) formulation was found to be more than 90%, whereas, it was less than 20% for unprocessed drugs. The results of DSC, PXRD and SEM, showed that the developed L-SNEDDS preconcentrate was successfully loaded onto the porous surface of probiotics, mushroom polysaccharides and Aerosil-200.

Background and Objective: Ferrous ascorbate (FA) is preferentially absorbed from the upper gastrointestinal (GI) track, and has low bioavailability due to less residence time of FA in upper GI track. In addition, FA has low solubility and stability at higher pH. The aim of this study was to prepare gastro-retentive tablets of FA in order to increase its gastric residence time and hence, bioavailability. Methods: Floating tablets of FA were prepared by wet granulation method using different retarding polymers, Povidone K30 as binder and sodium bicarbonate as effervescent agent. The prepared floating tablets were compared with immediate release (IR) tablets and characterized in detail for in vitro and in vivo studies. Results: In-vitro drug release study of the optimized batch showed 96% drug release in 12 h in 0.1 N HCl. The mechanism of drug release from the floating tablets was non-fickian and release kinetics was best fit in peppas model. The gastric retention time of optimized was found to be significantly increased (6 h) in comparison with IR tablet (70%) in comparison with IR tablet (15-30%). X-ray studies carried on healthy rabbits suggested that the optimized batch remained buoyant in gastric contents up to 6 h and pharmacokinetic study showed sustained released behaviour of optimized batch in comparison to conventional IR tablet. Conclusion: Floating tablet of FA improved the bioavailability of iron by increasing its gastric residence time, hence it could be a better approach for treating iron deficiency and help in improving the patient compliance than IR tablets.

Luliconazole is a new drug candidate for treatment of topical fungal infections. Its present therapy is associated with limitations of very poor and slow skin permeation, leading to required long term repeated administration for complete cure of disease. Lipid nanocarriers based elastic lipogel and ethogel formulations were developed in strength of 1% w/w and extensively characterized

The present study entails the toxicity evaluation of 7-methyl xanthine (7-MX), first of its kind molecule found effective in phase II clinical trials for the treatment of myopia, in comparison to other clinically used xanthines i.e., caffeine and theobromine. For acute toxicity evaluation, 7-MX was administered orally in two rodent species (rat and mice) at the doses of 300 mg/kg and 2000 mg/kg and for repeated dose 28-d oral toxicity, at 250, 500, and 1000 mg/kg in rats. Further, cellular toxicity was evaluated in normal breast epithelial (fR2), rat brain C6 glioma (C6 glioma) and human colorectal (Caco-2) cell lines. Also, the cell uptake assay to determine the intestinal permeability of drug was performed in Caco-2 cells. In acute toxicity, 7-MX treatment showed no mortality and toxicity, whereas 66.6% (mice) and 33.3% (rat) mortality was observed in both caffeine and theobromine treatment groups. In repeated dose 28-d oral toxicity, 7-MX treatment was found to have no-observed-adverse-effect level up to the dose of 1000 mg/kg in the present study conducted as per OECD guidelines 407. Also, very high IC

Clinically, Docosahexaenoic acid (DHA) has been implicated for the prevention of cognitive disorders and is considered as a vital component for normal brain development, especially in infants and c...

Exploration of dendrimers for effective drug delivery is giving promising results. The present study was designed and performed to explore the dendrimeric (polyamidoamine-lactoferrin; PAMAM-Lf) formulations for the effective rivastigmine (RIV) delivery against the Alzheimer’s induced animal model using lactoferrin as the targeting ligand. RIV delivery through PAMAM-Lf conjugates was highly efficient in the Alzheimer’s induced animal model. PAMAM-Lf conjugates also efficiently improved behavioral responses against the chemical memory deficit animal model as well as the Alzheimer’s induced animal model, separately. Behavioral responses revealed that motor and spatial memories were significantly improved (p < 0.005) over those from RIV alone. The latency time of PAMAM-Lf-RIV was 1.3 times higher over that of the pure RIV in the rotarod protocol, while it was 2.1-fold reduced in the Morris water maze test. The study also attempted to explore the mechanistic aspect of improved efficacy through biochemical eval...

In the present study, different in situ hydrogel formulations of docetaxel (DTX) based on biocompatible polymers such as Hyaluronic Acid (HA), poloxamer-407, chitosan and gellan gum were formulated to increase its therapeutic efficacy and reduce toxicity. DTX was loaded in nanovesicles (20 mg/mL equivalent to commercial strength) and further incorporated into the hydrogel bases to possess a dual rationale of protection against burst release and enhanced solubility of the drug. The optimized hydrogel formulation (NV-TPGS-3-GG-4) showed ideal rheological behavior and in situ characteristics at 37±0.5°C with sustained release of more than 144 h. The optimized formulation had instant in vitro gelation (2.8±0.3 min) with good injectability in comparison to the conventional commercial DTX injectable formulation having instant release (

The current study was designed to assess the in vivo hepatoprotective properties of trans-Anethole, which is a principal aromatic component of star anise. The hepatoprotective effects of trans-Anethole were evaluated at three doses [40, 80, and 160 mg/kg body weight (b.wt.)] against carbon tetrachloride (CCl

Background: Diclofenac Sodium (DS) injection is widely used in the management of acute or chronic pain and inflammatory diseases. It incorporates 20% w/v Transcutol-P as a solubilizer to make the stable injectable formulation. However, the use of Transcutol-P in high concentration leads to adverse effects such as severe nephrotoxicity, etc. Some advancements have resulted in the formulation of an aqueous-based injectable but that too used benzyl alcohol which is reported to be toxic for human use. Objective: This study aimed to develop an injectable Self-Micro Emulsifying Drug Delivery System (SMEDDS) as a novel carrier of DS for prompt release with better safety and efficacy. Methods: A solubility study was performed with different surfactants and co-surfactants. The conventional stirring method was employed for the formulation of SMEDDS. Detailed in vitro characterization was done for different quality control parameters. In vivo studies were performed using Wistar rats for pharmacokinetic evaluation, toxicological analysis, and analgesic activity. Results: The optimized formulation exhibited good physical stability, ideal globule size (156±0.4 nm), quick release, better therapeutics, and safety, increase in LD50 (221.9 mg/kg) to that of the commercial counterpart (109.9 mg/kg). Furthermore, pre-treatment with optimized formulation reduced the carrageenan-induced rat paw oedema by 88±1.2% after 4 h, compared to 77±1.6% inhibition with commercial DS formulation. Moreover, optimized formulation significantly (p< 0.05) inhibited the pain sensation in the acetic-acid induced writhing test in mice compared to its commercial equivalent with a better pharmacokinetic profile. Conclusion: The above findings confirmed that liquid SMEDDS can be a successful carrier for the safe and effective delivery of DS.

Onosma bracteata Wall. (Boraginaceae) is a highly valuable medicinal herb that is used for the treatment of fever, bronchitis, asthma, rheumatism, stomach irritation, and other inflammatory disorders. The present study aims to explore the hepatoprotective potential of ethanolic extract (Obeth) from O. bracteata aerial parts against carbon tetrachloride (CCl4) which causes hepatic damage in the male Wistar rats. Obeth showed effective radical quenching activity with an EC50 of 115.14 and 199.33 µg/mL in superoxide radical scavenging and lipid peroxidation analyses respectively along with plasmid DNA protective potential in plasmid nicking assay. The Obeth modulated mutagenicity of 2 Aminofluorine (2AF) in the pre-incubation mode of investigation (EC50 10.48 µg/0.1 mL/plate) in TA100 strain of Salmonella typhimurium. In in vivo studies, pretreatment of Obeth (50, 100, and 200 mg/kg) had the potential to normalize the biochemical markers aggravated by CCl4 (1mL/kg b.wt.) including liver antioxidative enzymes. Histopathological analysis also revealed the restoration of CCl4-induced liver histopathological alterations. Immunohistochemical studies showed that the treatment of Obeth downregulated the expression levels of p53 and cyclin D in hepatocytes. and downregulation in the Western blotting analysis revealed the downregulation of p-NF-kB, COX-2, and p53. HPLC data analysis showed the supremacy of major compounds namely, catechin, kaempferol, epicatechin, and Onosmin A in Obeth. The present investigation establishes the hepatoprotective and chemopreventive potential of O. bracteata against CCl4-induced hepatotoxicity via antioxidant defense system and modulation of the expression of proteins associated with the process of carcinogenesis in hepatic cells.

Diclofenac sodium is a potent NSAID, classified under BCS class II category having a poor aqueous solubility. Recently, its injectable formulation got banned and withdrawn from the market due to its severe nephrotoxicity caused by the use of synthetic surfactant, i.e. Transcutol-P as solubilizer. Therefore, the present study was aimed to prepare Transcutol-P free injectable using Vitamin E TPGS as a biosurfactant which is in list of inactive ingredients by US-FDA. Various cost effective aqueous injectable formulations were prepared by mixed solvency method that were characterized and optimized for different in vitro quality control parameters. Further, ex vivo hemolytic study showed the increased safety (23.4 ± 1.6%) of optimized formulation as compared with its commercial counterpart (100 ± 4.2%) at 75 mg/ml. Furthermore, in vivo acute and sub-acute toxicity study demonstrated an increase in LD50 to 123.75 ± 6.2 mg/kg to that of a commercial counterpart (109.96 ± 5.5 mg/kg). In addition, optimized formulation demonstrated better mean residence time and area under curve when compared with commercial test group, respectively. Moreover, optimized formulation was also evaluated for its therapeutic efficacy. The results obtained from acetic acid-induced writhing test in albino mice showed 78 ± 2.1% protection from writhes after 120 min, whereas the commercial formulation had only 48.3 ± 1.9% protection. Additionally, carrageenan-induced rat paw edema model also confirmed the better anti-inflammatory activity of optimized aqueous injectable formulation than its commercial counterpart. Thus, the developed aqueous injectable formulation of diclofenac is free from toxic Transcutol-P with enhanced safety and therapeutic efficacy.

Background: Surfactants are an important category of additives that are used widely in most of the formulations as solubilizers, stabilizers, and emulsifiers. Current drug delivery systems comprise of numerous synthetic surfactants (such as Cremophor EL, polysorbate 80, Transcutol-P), which are associated with several side effects though used in many formulations. Therefore, to attenuate the problems associated with conventional surfactants, a new generation of surface-active agents is obtained from the metabolites of fungi, yeast, and bacteria, which are termed as biosurfactants. Objectives: In this article, we critically analyze the different types of biosurfactants, their origin along with their chemical and physical properties, advantages, drawbacks, regulatory status, and detailed pharmaceutical applications. Methods: 243 papers were reviewed and included in this review. Results: Briefly, Biosurfactants are classified as glycolipids, rhamnolipids, sophorolipids, trehalolipids, surfactin, lipopeptides & lipoproteins, lichenysin, fatty acids, phospholipids, and polymeric biosurfactants. These are amphiphilic biomolecules with lipophilic and hydrophilic ends and are used as drug delivery vehicles (foaming, solubilizer, detergent, and emulsifier) in the pharmaceutical industry. Despite additives, they have some biological activity as well (anti-cancer, anti-viral, anti-microbial, P-gp inhibition, etc.). These biomolecules possess better safety profiles and are biocompatible, biodegradable, and specific at different temperatures. Conclusion: Biosurfactants exhibit good biomedicine and additive properties that can be used in developing novel drug delivery systems. However, more research should be driven due to the lack of comprehensive toxicity testing and high production cost which limits their use.

Diabetic retinopathy (DR) remains the leading cause of blindness in working-aged adults around the world. The proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) are the severe vision threatening stages of the disorder. Although, a huge body of research exists in elaborating the pathological mechanisms that lead to the development of DR, the certainty and the correlation amongst these pathways remain ambiguous. The complexity of DR lies in the multifactorial pathological perturbations that are instrumental in both the disease development and its progression. Therefore, a holistic perspective with an understanding of these pathways and their correlation may explain the pathogenesis of DR as a unifying mechanism. Hyperglycemia, oxidative stress and inflammatory pathways are the crucial components that are implicated in the pathogenesis of DR. Of these, hyperglycemia appears to be the initiating central component around which other pathological processes operate. Thus, this review discusses the role of hyperglycemia, oxidative stress and inflammation in the pathogenesis of DR, and highlights the cross-talk amongst these pathways in an attempt to understand the complex interplay of these mechanisms. Further, an effort has been made to identify the knowledge gap and the key players in each pathway that may serve as potential therapeutic drug targets.

BACKGROUND Systemic biochemical disarray has been implicated in the pathogenesis and progression of diabetes and its complications. However, the modifications in the metabolic state of the retina and its microenvironment in response to the systemic metabolic malfunction has not been documented. OBJECTIVE The objective of the present study was to document the various biomarkers that may be involved in the pathogenesis and progression of Proliferative Diabetic Retinopathy (PDR). METHOD The vitreous humour and plasma samples from 38 PDR, 7 Proliferative Vitreo Retinopathy (PVR) and 17 control patients undergoing pars plana vitrectomy were analysed for sixteen different biomarkers. Whole genome Single Nucleotide Polymorphism (SNP) microarray was performed on ten PDR patients' peripheral blood samples. RESULTS The vitreous humour glucose, creatinine, micro protein, phosphorus and lactate dehydrogenase were found significantly increased in the PDR patients compared to controls. The plasma urea, creatinine and micro protein were also significantly increased. The plasma phosphorus of PDR patients on oral hypoglycemic therapy was found significantly decreased compared with PDR patients on insulin therapy and controls. SNPs previously associated with glucose (5), lactate dehydrogenase (2) and creatinine (2) levels were identified to be polymorphic homozygous (minor allele) in ≥ 60% patients in this study, suggesting enhanced susceptibility. CONCLUSION The metabolic overactivity of the retinal microenvironment appears to play a vital role in the pathogenesis of PDR. The significantly elevated biomarkers may have diagnostic, prognostic and therapeutic significance. These findings shed light on the biochemical disarray in the vitreous humour of PDR patients that could have significant management implications.

In the present study, different solid self-nanoemulsifying drug delivery system (S-SNEDDS) was formulated by using porous hydrophilic and hydrophobic carriers to improve the dissolution rate and bioavailability of simvastatin (SIM). The prepared liquid-SNEDDS composed of Labrafil M 1944 CS/ Tween-80/ Ethanol (20% / 53.33%/26.67% v/v) with 0.1% SIM, resulted droplet size of 40.69 nm. The hydrophobic carriers used were Aerosil-200, Syloid 244FP, Syloid XDP 3150, Magnesium stearate, Micro Crystalline Cellulose PH102 and lactose and hydrophilic carriers used were Poly vinyl alcohol, Sodium carboxy methyl cellulose and hydroxypropyl-β-cyclodextrin. These S-SNEDDS were characterized through micromeritic, biopharmaceutical studies and stability studies. The spray dried S-SNEDDS prepared by using Aerosil 200 as hydrophobic carrier provided nanoemulsions with unchanged droplet size and drug release when subjected at different stress conditions such as thermodynamic stress and freeze thaw cycles. In vitro dissolution studies revealed that the L-SNEDDS and S-SNEDDS of Aerosil 200 were found to be remarkably superior over the unprocessed SIM and marketed SIM. Scanning electron microscope, Differential scanning calorimeter and Powder X-Ray Diffraction revealed crystalline SIM was present in a changed amorphous state in the SNEDDS formulations prepared with Aerosil 200 as carrier. Further, pharmacokinetic study carried out on rats revealed 0.5 h increase in time for maximal concentration (Tmax), 3.75 folds increase in maximal concentration (Cmax), 1.22 h increase in mean residence time, 1.54 folds increase in area under curve (AUC0-t), 2.10 folds increase in AUC0-∞ and 3.28 folds increase in bioavailability confirms that the developed S-SNEDDS were superior than that of marketed formulation. Hence, it can be safely concluded that Aerosil 200 based S-SNEDDS were able to provide improvement in dissolution rate and oral bioavailability of SIM.

Development of self-nanoemulsifying drug delivery systems (SNEDDS) of glimepiride is reported with the aim to achieve its oral delivery. Lauroglycol FCC, Tween-80, and ethanol were used as oil, surfactant, and co-surfactant, respectively as independent variables. The optimized composition of SNEDDS formulation (F1) was 10% v/v Lauroglycol FCC, 45% v/v Tween 80, 45% v/v ethanol, and 0.005% w/v glimepiride. Further, the optimized liquid SNEDDS were solidified through spray drying using various hydrophilic and hydrophobic carriers. Among the various carriers, Aerosil 200 was found to provide desirable flow, compression, dissolution, and diffusion. Both, liquid and solid-SNEDDS have shown release of more than 90% within 10 min. Results of permeation studies performed on Caco-2 cell showed that optimized SNEDDS exhibited 1.54 times higher drug permeation amount and 0.57 times lower drug excretion amount than that of market tablets at 4 hours (p .01). Further, the cytotoxicity study performed on Caco-2 cell revealed that the cell viability was lower in SNEDDS (92.22% ± 4.18%) compared with the market tablets (95.54% ± 3.22%; p .05, i.e. 0.74). The formulation was found stable with temperature variation and freeze thaw cycles in terms of droplet size, zeta potential, drug precipitation and phase separation. Crystalline glimepiride was observed in amorphous state in solid SNEDDS when characterized through DSC, PXRD, and FT-IR studies. The study revealed successful formulation of SNEDDS for glimepiride.

Pyran is an oxygen-containing heterocyclic moiety, which exhibits an array of pharmacological properties. Pyran is also one of the important structural subunits found widely in natural products, e.g. coumarins, benzopyrans, sugars, flavonoids, xanthones, etc. The diverse anticancer capabilities of pyrans have been additionally evidenced by the fact that this heterocycle has recently been a focal point for researchers worldwide. This review provides a summary of pyran-based anticancer compounds, with emphasis on the past 10 years. It focuses on advancements in the field of naturally occurring pyrans as anticancer agents. The discussion also includes structure–activity relationships, along with the structures of the most promising molecules, their biological activities against several human cancer cell lines, as well as mechanistic insights discovered through the pharmacological evaluation and molecular modeling of pyran-based molecules. The promising activities revealed by these pyran-based scaffolds undoubtedly place them at the forefront for the discovery of prospective drug candidates. Thus, they could therefore be of great interest to researchers working on the synthesis of antitumour drug candidates.

Aim: The present work focused on the development of sustained-release microsphere formulation of cefixime to provide reduction in dosing frequency, improved antibacterial activity and patient compliance. Methodology & results: Microspheres were prepared by modified emulsion solvent evaporation method and evaluated by in vitro and in vivo studies. Optimized formulation (FK-07) was found to have entrapment efficiency of 81.12 ± 0.93% and particle size of 166.82 ± 0.86 μm. FK-07 sustained release up to 24 h as demonstrated by in vitro drug release and in vivo pharmacokinetic study in rats. FK-07 showed approximately twofold increase in bioavailability and twofold decrease in MIC90 value against Escherichia coli, Klebsiella pneumoniae and Salmonella typhi in comparison to marketed formulation. Conclusion: Sustaining the release of cefixime using microspheres enhanced its bioavailability, antibacterial efficacy and will help in reducing its dosing frequency.

Docosahexaenoic Acid (DHA) is an essential polyunsaturated omega-3 fatty acid, and a fundamental structural component of the phospholipid membranes, especially of neural and retinal cells. DHA is found to be critical for the normal development and functioning of neurons and synaptogenesis in the brain, and is required during pre- and post-natal stages of life. DHA has also been observed to exhibit neuroprotective, cardioprotective, and anti-inflammatory properties. However, geographical dietary variations and poor economic conditions lead to insufficient DHA levels resulting in various health deficits like improper brain development, cognitive disorders, and other clinical complications. Thus, to prevent its deficiency-induced derangements, several authorities recommend DHA as a supplement during pregnancy, infancy, and throughout adulthood. In past decades, the soft gelatin capsule was only feasible resolute of DHA, but due to their limitations and invention of new technologies; it led to the development of new dosage forms with improved physicochemical characteristics of DHA. This article will discuss in detail about the role of DHA in brain development, microalgae oil as an emerging source of DHA, clinical- and pharmacological-activities of DHA, issues related to DHA oil, current formulation of DHA along with their application, limitations, and strategies used for improvement and future prospectives.

This study aimed to develop microsponges based topical gel formulation of 5-Fluorouracil (5-FU) for the treatment of skin cancer with enhanced skin deposition and reduced skin irritation potential. Microsponges were prepared by Quasi-emulsion solvent diffusion method using ethyl cellulose and Eudragit RL 30 D; and was optimised through detailed

The screening of aqueous extract of Clerodendrum serratum revealed its broad-spectrum antimicrobial potential against Gram positive, Gram negative bacteria, and yeast. Optimizing the extraction strategies, revealed 15% concentration of aqueous extract prepared at 40 °C by extracting for 40 min, as optimum parameters and its statistical optimization by Box–Behnken design led to 1.16–1.35 folds enhancement in activity. Organic solvent extraction further improved the activity where methanol proved to be the best organic extractant which was effective against all the 13 pathogens tested with inhibition zone ranging from 14 to 32 mm. Minimum Inhibitory Concentration (MIC) study endorsed the methanolic extract to be the best organic extractant, as it showed the lowest MIC (0.5–10 mg/ml) in comparison to aqueous extract (1–10 mg/ml) as well as Partially Purified Phytoconstituents i.e., flavonoids (1–5 mg/ml), diterpenes (5–10 mg/ml) and cardiac glycosides (5–10 mg/ml). All these were found to be biosafe in both In-vitro (Ames and MTT assay) and In-vivo toxicity studies. Acute oral toxicity testing of flavonoids (2000 mg/ml) on Wistar rats did not reveal any significant change in relative organ weight, biochemical, hematological parameters and organs’ architecture in comparison to control. Antiproliferative potential of flavonoids against human cancerous cell lines i.e., HeLa, HCT-15, and U87-MG, further increase the importance of this plant as a promising candidate for drug development. The overall study justified the medicinal importance of this plant.