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  1. Fulltext Correction: Aljabali, A.A.A.; et al. Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer via down Regulation of Nuclear p65 and HIF-1α. Cancers 2020, 12, 113
    Aljabali AAA, Bakshi HA, Hakkim FL, Haggag YA, Al-Batanyeh KM, Zoubi MSA, et al.
    Cancers (Basel), 2020 Nov 30;12(12).
    PMID: 33266353 DOI: 10.3390/cancers12123587
    The authors wish to make the following corrections to this paper [...].
  2. Fulltext Dynamics of Prolyl Hydroxylases Levels During Disease Progression in Experimental Colitis
    Bakshi HA, Mishra V, Satija S, Mehta M, Hakkim FL, Kesharwani P, et al.
    Inflammation, 2019 Dec;42(6):2032-2036.
    PMID: 31377947 DOI: 10.1007/s10753-019-01065-3
    Hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitors are shown to be protective in several models of inflammatory bowel disease (IBD). However, these non-selective inhibitors are known to inhibit all the three isoforms of PHD, i.e. PHD-1, PHD-2 and PHD-3. In the present report, we investigated the associated changes in levels of PHDs during the development and recovery of chemically induced colitis in mice. The results indicated that in the experimental model of murine colitis, levels of both, PHD-1 and PHD-2 were found to be increased with the progression of the disease; however, the level of PHD-3 remained the same in group of healthy controls and mice with colitis. Thus, the findings advocated that inhibitors, which inhibited all three isoforms of PHD could not be ideal therapeutics for IBD since PHD-3 is required for normal gut function. Hence, this necessitates the development of new compounds capable of selectively inhibiting PHD-1 and PHD-2 for effective treatment of IBD.
  3. Rising horizon in circumventing multidrug resistance in chemotherapy with nanotechnology
    Choudhury H, Pandey M, Yin TH, Kaur T, Jia GW, Tan SQL, et al.
    Mater Sci Eng C Mater Biol Appl, 2019 Aug;101:596-613.
    PMID: 31029353 DOI: 10.1016/j.msec.2019.04.005
    Multidrug resistance (MDR) is one of the key barriers in chemotherapy, leading to the generation of insensitive cancer cells towards administered therapy. Genetic and epigenetic alterations of the cells are the consequences of MDR, resulted in drug resistivity, which reflects in impaired delivery of cytotoxic agents to the cancer site. Nanotechnology-based nanocarriers have shown immense shreds of evidence in overcoming these problems, where these promising tools handle desired dosage load of hydrophobic chemotherapeutics to facilitate designing of safe, controlled and effective delivery to specifically at tumor microenvironment. Therefore, encapsulating drugs within the nano-architecture have shown to enhance solubility, bioavailability, drug targeting, where co-administered P-gp inhibitors have additionally combat against developed MDR. Moreover, recent advancement in the stimuli-sensitive delivery of nanocarriers facilitates a tumor-targeted release of the chemotherapeutics to reduce the associated toxicities of chemotherapeutic agents in normal cells. The present article is focused on MDR development strategies in the cancer cell and different nanocarrier-based approaches in circumventing this hurdle to establish an effective therapy against deadliest cancer disease.
  4. Silver nanoparticles: Advanced and promising technology in diabetic wound therapy
    Choudhury H, Pandey M, Lim YQ, Low CY, Lee CT, Marilyn TCL, et al.
    Mater Sci Eng C Mater Biol Appl, 2020 Jul;112:110925.
    PMID: 32409075 DOI: 10.1016/j.msec.2020.110925
    Wounds associated with diabetes mellitus are the most severe co-morbidities, which could be progressed to cause cell necrosis leading to amputation. Statistics on the recent status of the diabetic wounds revealed that the disease affects 15% of diabetic patients, where 20% of them undergo amputation of their limb. Conventional therapies are found to be ineffective due to changes in the molecular architecture of the injured area, urging novel deliveries for effective treatment. Therefore, recent researches are on the development of new and effective wound care materials. Literature is evident in providing potential tools in topical drug delivery for wound healing under the umbrella of nanotechnology, where nano-scaffolds and nanofibers have shown promising results. The nano-sized particles are also known to promote healing of wounds by facilitating proper movement through the healing phases. To date, focuses have been made on the efficacy of silver nanoparticles (AgNPs) in treating the diabetic wound, where these nanoparticles are known to exploit potential biological properties in producing anti-inflammatory and antibacterial activities. AgNPs are also known to activate cellular mechanisms towards the healing of chronic wounds; however, associated toxicities of AgNPs are of great concern. This review is an attempt to illustrate the use of AgNPs in wound healing to facilitate this delivery system in bringing into clinical applications for a superior dressing and treatment over wounds and ulcers in diabetes patients.
  5. Recent Updates on Novel Approaches in Insulin Drug Delivery: A Review of Challenges and Pharmaceutical Implications
    Pandey M, Choudhury H, Yi CX, Mun CW, Phing GK, Rou GX, et al.
    Curr Drug Targets, 2018;19(15):1782-1800.
    PMID: 29792143 DOI: 10.2174/1389450119666180523092100
    Diabetes mellitus, a metabolic disorder of glucose metabolism, is mainly associated with insulin resistance to the body cells, or impaired production of insulin by the pancreatic β-cells. Insulin is mainly required to regulate glucose metabolism in type 1 diabetes mellitus patients; however, many patients with type 2 diabetes mellitus also require insulin, especially when their condition cannot be controlled solely by oral hypoglycemic agents. Hence, major research is ongoing attempting to improve the delivery of insulin in order to make it more convenient to patients who experience side effects from the conventional treatment procedure or non-adherence to insulin regimen due to multiple comorbid conditions. Conventionally, insulin is administered via subcutaneous route which is also one of the sole reasons of patient's non-compliance due to the invasiveness of this method. Several attempts have been done to improve patient compliance, reduce side effects, improve delivery adherence, and to enhance the pharmaceutical performance of the insulin therapy. Despite facing substantial challenges in developing efficient delivery systems for insulin, vast research studies have been carried out for the development of smart delivery systems to deliver insulin via ocular, buccal, pulmonary, oral, transdermal, as well as rectal routes. Therefore, the present review was aimed to overview the challenges encountered with the current insulin delivery systems and to summarize recent advancements in technology of various novel insulin delivery systems being discovered and introduced in the current market.
  6. Perspectives of Nanoemulsion Strategies in The Improvement of Oral, Parenteral and Transdermal Chemotherapy
    Pandey M, Choudhury H, Yeun OC, Yin HM, Lynn TW, Tine CLY, et al.
    Curr Pharm Biotechnol, 2018;19(4):276-292.
    PMID: 29874994 DOI: 10.2174/1389201019666180605125234
    BACKGROUND: Targeting chemotherapeutic agents to the tumor tissues and achieving accumulation with ideal release behavior for desired therapy requires an ideal treatment strategy to inhibit division of rapid growing cancerous cells and as an outcome improve patient's quality of life. However, majority of the available anticancer therapies are well known for their systemic toxicities and multidrug resistance.

    METHODS: Application of nanotechnology in medicine have perceived a great evolution during past few decades. Nanoemulsion, submicron sized thermodynamically stable distribution of two immiscible liquids, has gained extensive importance as a nanocarrier to improve chemotherapies seeking to overcome the limitations of drug solubilization, improving systemic delivery of the chemotherapeutics to the site of action to achieve a promising inhibitory in tumor growth profile with reduced systemic toxicity.

    RESULTS AND CONCLUSION: This review has focused on potential application of nanoemulsion in the translational research and its role in chemotherapy using oral, parenteral and transdermal route to enhance systemic availability of poorly soluble drug. In summary, nanoemulsion is a multifunctional nanocarrier capable of enhancing drug delivery potential of cytotoxic agents, thereby, can improve the outcomes of cancer treatment by increasing the life-span of the patient and quality of life, however, further clinical research and characterization of interactive reactions should need to be explored.

  7. Transferrin receptors-targeting nanocarriers for efficient targeted delivery and transcytosis of drugs into the brain tumors: a review of recent advancements and emerging trends
    Choudhury H, Pandey M, Chin PX, Phang YL, Cheah JY, Ooi SC, et al.
    Drug Deliv Transl Res, 2018 10;8(5):1545-1563.
    PMID: 29916012 DOI: 10.1007/s13346-018-0552-2
    Treatment of glioblastoma multiforme (GBM) is a predominant challenge in chemotherapy due to the existence of blood-brain barrier (BBB) which restricts delivery of chemotherapeutic agents to the brain together with the problem of drug penetration through hard parenchyma of the GBM. With the structural and mechanistic elucidation of the BBB under both physiological and pathological conditions, it is now viable to target central nervous system (CNS) disorders utilizing the presence of transferrin (Tf) receptors (TfRs). However, overexpression of these TfRs on the GBM cell surface can also help to avoid restrictions of GBM cells to deliver chemotherapeutic agents within the tumor. Therefore, targeting of TfR-mediated delivery could counteract drug delivery issues in GBM and create a delivery system that could cross the BBB effectively to utilize ligand-conjugated drug complexes through receptor-mediated transcytosis. Hence, approach towards successful delivery of antitumor agents to the gliomas has been making possible through targeting these overexpressed TfRs within the CNS and glioma cells. This review article presents a thorough analysis of current understanding on Tf-conjugated nanocarriers as efficient drug delivery system.
  8. Current attempts to implement microRNA-based diagnostics and therapy in cardiovascular and metabolic disease: a promising future
    Thanikachalam PV, Ramamurthy S, Wong ZW, Koo BJ, Wong JY, Abdullah MF, et al.
    Drug Discov Today, 2018 Mar;23(3):460-480.
    PMID: 29107764 DOI: 10.1016/j.drudis.2017.10.020
    MicroRNAs (miRNAs) are small, noncoding RNAs regulating gene expression at the post-translational level. miRNA-based therapeutic agents are important because of the functionality of miRNAs in regulating lipid and glucose metabolism and their role in the pathogenesis of metabolic disorders such as diabetes and obesity, where dysregulation leads to disease; they are also important in angiogenesis. miRNAs additionally serve as biomarkers in the diagnosis, prognosis and risk assessment of disease and in monitoring the response to treatment. Here, we provide a brief overview of progress in miRNA-based therapeutics in the preclinical and clinical setting and highlight the novel outcomes and opportunities in the diagnosis and treatment of metabolic conditions. In addition, we present the role of miRNAs in stem cell therapy which could have great potential in regenerative medicine.
  9. Nanotechnology based approaches for anti-diabetic drugs delivery
    Kesharwani P, Gorain B, Low SY, Tan SA, Ling ECS, Lim YK, et al.
    Diabetes Res Clin Pract, 2018 Feb;136:52-77.
    PMID: 29196152 DOI: 10.1016/j.diabres.2017.11.018
    Nanotechnology science has been diverged its application in several fields with the advantages to operate with nanometric range of objects. Emerging field of nanotechnology has been also being approached and applied in medical biology for improved efficacy and safety. Increased success in therapeutic field has focused several approaches in the treatment of the common metabolic disorder, diabetes. The development of nanocarriers for improved delivery of different oral hypoglycemic agents compared to conventional therapies includes nanoparticles (NPs), liposomes, dendrimer, niosomes and micelles, which produces great control over the increased blood glucose level and thus becoming an eye catching and most promising technology now-a-days. Besides, embellishment of nanocarriers with several ligands makes it more targeted delivery with the protection of entrapped hypoglycaemic agents against degradation, thereby optimizing prolonged blood glucose lowering effect. Thus, nanocarriers of hypoglycemic agents provide the aim towards improved diabetes management with minimized risk of acute and chronic complications. In this review, we provide an overview on distinctive features of each nano-based drug delivery system for diabetic treatment and current NPs applications in diabetes management.
  10. Current appraises of therapeutic applications of nanocurcumin: A novel drug delivery approach for biomaterials in dentistry
    Bapat RA, Bedia SV, Bedia AS, Yang HJ, Dharmadhikari S, Abdulla AM, et al.
    Environ Res, 2023 Dec 01;238(Pt 1):116971.
    PMID: 37717805 DOI: 10.1016/j.envres.2023.116971
    Curcumin is a natural herb and polyphenol that is obtained from the medicinal plant Curcuma longa. It's anti-bacterial, anti-inflammatory, anti-cancer, anti-mutagenic, antioxidant and antifungal properties can be leveraged to treat a myriad of oral and systemic diseases. However, natural curcumin has weak solubility, limited bioavailability and undergoes rapid degradation, which severely limits its therapeutic potential. To overcome these drawbacks, nanocurcumin (nCur) formulations have been developed for improved biomaterial delivery and enhanced treatment outcomes. This novel biomaterial holds tremendous promise for the treatment of various oral diseases, the majority of which are caused by dental biofilm. These include dental caries, periodontal disease, root canal infection and peri-implant diseases, as well as other non-biofilm mediated oral diseases such as oral cancer and oral lichen planus. A number of in-vitro studies have demonstrated the antibacterial efficacy of nCur in various formulations against common oral pathogens such as S. mutans, P. gingivalis and E. faecalis, which are strongly associated with dental caries, periodontitis and root canal infection, respectively. In addition, some clinical studies were suggestive of the notion that nCur can indeed enhance the clinical outcomes of oral diseases such as periodontitis and oral lichen planus, but the level of evidence was very low due to the small number of studies and the methodological limitations of the available studies. The versatility of nCur to treat a diverse range of oral diseases augurs well for its future in dentistry, as reflected by rapid pace in which studies pertaining to this topic are published in the scientific literature. In order to keep abreast of the latest development of nCur in dentistry, this narrative review was undertaken. The aim of this narrative review is to provide a contemporaneous update of the chemistry, properties, mechanism of action, and scientific evidence behind the usage of nCur in dentistry.
  11. Fulltext An update on natural compounds in the remedy of diabetes mellitus: A systematic review
    Choudhury H, Pandey M, Hua CK, Mun CS, Jing JK, Kong L, et al.
    J Tradit Complement Med, 2018 Jul;8(3):361-376.
    PMID: 29992107 DOI: 10.1016/j.jtcme.2017.08.012
    Herbal medicine, phytomedicine or botanical medicine are synonymous, utilizes plants intended for medicinal purposes. Medicinal use of herbal medicine in the treatment and prevention of diseases including diabetes has a long history compared to conventional medicine. Diabetes is one of the major public health concerns over the world. Diabetes or hyperglycemia is considered to be one of the common public health hazard; optimal control of which is still not possible. Persistent hyperglycemia or uncontrolled diabetes has the potential to cause serious complications such as kidney disease, vision loss, cardiovascular disease, and lower-limb amputations which contributed towards morbidity and mortality in diabetes. There are various approaches to treat and prevent diabetes as well as its secondary complications, one of it is herbal medicines. However, the selection of herbs might depends on several factors, which include the stage of progression of diabetes, types of comorbidities that the patients are having, availability, affordability as well as the safety profile of the herbs. This review focuses on the herbal and natural remedies that play the role in the treatment or prevention of this morbid disorder - diabetes, including their underlying mechanisms for the blood glucose-lowering property and the herbal products already been marketed for the remedial action of diabetes.
  12. Recent update on potential cytotoxicity, biocompatibility and preventive measures of biomaterials used in dentistry
    Bapat RA, Parolia A, Chaubal T, Dharamadhikari S, Abdulla AM, Sakkir N, et al.
    Biomater Sci, 2021 May 04;9(9):3244-3283.
    PMID: 33949464 DOI: 10.1039/d1bm00233c
    Dental treatment is provided for a wide variety of oral health problems like dental caries, periodontal diseases, periapical infections, replacement of missing teeth and orthodontic problems. Various biomaterials, like composite resins, amalgam, glass ionomer cement, acrylic resins, metal alloys, impression materials, bone grafts, membranes, local anaesthetics, etc., are used for dental applications. The physical and chemical characteristics of these materials influence the outcome of dental treatment. It also impacts on the biological, allergic and toxic potential of biomaterials. With innovations in science and their positive results, there is also a need for awareness about the biological risks of these biomaterials. The aim of dental treatment is to have effective, yet safe, and long-lasting results for the benefit of patients. For this, it is important to have a thorough understanding of biomaterials and their effects on local and systemic health. Materials used in dentistry undergo a series of analyses before their oral applications. To the best of our knowledge, this is the first and original review that discusses the reasons for and studies on the toxicity of commonly used biomaterials for applications in dentistry. It will help clinicians to formulate a methodical approach for the selection of dental biomaterials, thus providing an awareness for forecasting their risk of toxic reactions.
  13. Formulation development and characterization of lumefantrine nanosuspension for enhanced antimalarial activity
    Shah R, Soni T, Shah U, Suhagia BN, Patel MN, Patel T, et al.
    J Biomater Sci Polym Ed, 2021 05;32(7):833-857.
    PMID: 33380264 DOI: 10.1080/09205063.2020.1870378
    Variable and low oral bioavailability (4-11%) of lumefantrine (LUF), an anti-malarial agent, is characterized by very low solubility in aqueous vehicle. Thus, the present study was intended to formulate lyophilized nanosuspensions of LUF to resolve its solubility issues for the improvement of oral bioavailability. A three level 32 factorial design was applied to analyze the influence of independent variables, concentration of polysorbate 80 (X1) and sonication time (X2) on the responses for dependent variables, particle size (Y1) and time to 90% release of LUF (t90) (Y2). Optimized formulation (F3) has shown to possess lowest particle size (95.34 nm) with minimum t90 value (⁓3 mins), which was lyophilized to obtain the dry powder form of the nanosuspension. The characterization parameters confirmed the amorphous form of LUF with good stability and no chemical interactions of the drug with the incorporated components. Further, saturation solubility study revealed increased solubility of the LUF nanosuspension (1670 µg/mL) when compared to the pure drug (212.33 µg/mL). Further, rate of dissolution of LUF from the nanosuspension formulations were found to be significantly (p 
  14. Methotrexate and beta-carotene loaded-lipid polymer hybrid nanoparticles: a preclinical study for breast cancer
    Jain A, Sharma G, Kushwah V, Garg NK, Kesharwani P, Ghoshal G, et al.
    Nanomedicine (Lond), 2017 Aug;12(15):1851-1872.
    PMID: 28703643 DOI: 10.2217/nnm-2017-0011
    AIM: This work was intended to investigate the targeting potential of fructose-tethered lipid-polymeric hybrid nanoparticles (F-BC-MTX-LPHNPs) co-loaded with beta carotene (BC) and methotrexate (MTX) in breast cancer therapeutics and find out the possible protective role of BC on MTX-induced toxicity.

    MATERIALS & METHODS: F-BC-MTX-LPHNPs were fabricated using self-assembled nano-precipitation technique. Fructose was conjugated on the surface of the particles. The in vitro cytotoxicity, sub-cellular localization and apoptotic activity of F-BC-MTX-LPHNPs were evaluated against MCF-7 breast cancer cells. The antitumor potential of F-BC-MTX-LPHNPs was further studied.

    RESULTS & CONCLUSION: Outcomes suggested that F-BC-MTX-LPHNPs induced the highest apoptosis index (0.89) against MCF-7 cells. Following 30 days of treatment, the residual tumor progression was assessed to be approximately 32%, in animals treated with F-BC-MTX-LPHNPs. F-BC-MTX-LPHNPs are competent to selectively convey the chemotherapeutic agent to the breast cancers. Beta carotene ameliorated MTX-induced hepatic and renal toxicity.

  15. Clathrin-mediated endocytic uptake of PUFA enriched self-nanoemulsifying lipidic systems (SNELS) of an anticancer drug against triple negative cancer and DMBA induced preclinical tumor model
    Khurana RK, Kumar R, Gaspar BL, Welsby G, Welsby P, Kesharwani P, et al.
    Mater Sci Eng C Mater Biol Appl, 2018 Oct 01;91:645-658.
    PMID: 30033299 DOI: 10.1016/j.msec.2018.05.010
    The current studies envisage unravelling the underlying cellular internalisation mechanism of the systematically developed docetaxel (DTH) polyunsaturated fatty acid (PUFA) enriched self-nanoemulsifying lipidic micellar systems (SNELS). The concentration-, time- and cytotoxicity-related effects of DTH-SNELS on triple negative breast cancer (TNBC) MDA-MB-231 and non-TNBC MCF-7 cell lines were assessed through Presto-blue assay. Subsequently, rhodamine-123 (Rh-123) loaded SNELS were employed for evaluating their internalisation through flow cytometry and fluorescence microscopy, establishing it to be "clathrin-mediated" endocytic pathway. Apoptosis assay (65% cell death) and cell cycle distribution (47% inhibition at G2/M phase) further corroborated the cytotoxicity of DTH-SNELS towards cancerous cells. Biodistribution, histopathology and haematology studies indicated insignificant toxicity of the optimized formulation on vital organs. Preclinical anticancer efficacy studies using 7,12-dimethylbenzantracene (DMBA)-induced model construed significant reduction in breast tumor-volume. Overall, extensive in vitro and in vivo studies indicated the intracellular localization and cytotoxicity, suggesting DTH-SNELS as promising delivery systems for breast tumor therapeutics including TNBC.
  16. The use of nanoparticles as biomaterials in dentistry
    Bapat RA, Joshi CP, Bapat P, Chaubal TV, Pandurangappa R, Jnanendrappa N, et al.
    Drug Discov Today, 2019 01;24(1):85-98.
    PMID: 30176358 DOI: 10.1016/j.drudis.2018.08.012
    Maintenance of oral health is a major challenge in dentistry. Different materials have been used to treat various dental diseases, although treatment success is limited by features of the biomaterials used. To overcome these limitations, materials incorporated with nanoparticles (NPs) can be used in dental applications including endodontics, periodontics, tissue engineering, oral surgery, and imaging. The unique properties of NPs, including their surface:volume ratio, antibacterial action, physical, mechanical, and biological characteristics, and unique particle size have rendered them effective vehicles for dental applications. In this review, we provide insights into the various applications of NPs in dentistry, including their benefits, limitations, properties, actions and future potential.
  17. The potential of dendrimer in delivery of therapeutics for dentistry
    Bapat RA, Dharmadhikari S, Chaubal TV, Amin MCIM, Bapat P, Gorain B, et al.
    Heliyon, 2019 Oct;5(10):e02544.
    PMID: 31687479 DOI: 10.1016/j.heliyon.2019.e02544
    Dendrimers are hyperbranched nanoparticle structures along with its surface modifications can to be used in dental biomaterials for biomimetic remineralisation of enamel and dentin. The review highlights the therapeutic applications of dendrimers in the field of dentistry. It addresses the possible mechanisms of enhancement of mechanical properties of adhesives and resins structure. Dendrimers due to its unique construction of possessing inner hydrophobic and outer hydrophilic structure can act as drug carrier for delivery of antimicrobial drugs for treatment of periodontal diseases and at peripheral dental implant areas. Dendrimers due to its hyperbranched structures can provides a unique drug delivery vehicle for delivery of a drug at specific site for sustained release for therapeutic effects. Thus, dendrimers can be one of the most important constituents which can be incorporated in dental biomaterials for better outcomes in dentistry.
  18. Nucleic Acid Aptamers as a Potential Nucleus Targeted Drug Delivery System
    Shrivastava G, Bakshi HA, Aljabali AA, Mishra V, Hakkim FL, Charbe NB, et al.
    Curr Drug Deliv, 2020;17(2):101-111.
    PMID: 31906837 DOI: 10.2174/1567201817666200106104332
    BACKGROUND: Nucleus targeted drug delivery provides several opportunities for the treatment of fatal diseases such as cancer. However, the complex nucleocytoplasmic barriers pose significant challenges for delivering a drug directly and efficiently into the nucleus. Aptamers representing singlestranded DNA and RNA qualify as next-generation highly advanced and personalized medicinal agents that successfully inhibit the expression of certain proteins; possess extraordinary gene-expression for manoeuvring the diseased cell's fate with negligible toxicity. In addition, the precisely directed aptamers to the site of action present a tremendous potential to reach the nucleus by escaping the ensuing barriers to exhibit a better drug activity and gene expression.

    OBJECTIVE: This review epigrammatically highlights the significance of targeted drug delivery and presents a comprehensive description of the principal barriers faced by the nucleus targeted drug delivery paradigm and ensuing complexities thereof. Eventually, the progress of nucleus targeting with nucleic acid aptamers and success achieved so far have also been reviewed.

    METHODS: Systematic literature search was conducted of research published to date in the field of nucleic acid aptamers.

    CONCLUSION: The review specifically points out the contribution of individual aptamers as the nucleustargeting agent rather than aptamers in conjugated form.

  19. Systematic review of metformin monotherapy and dual therapy with sodium glucose co-transporter 2 inhibitor (SGLT-2) in treatment of type 2 diabetes mellitus
    Molugulu N, Yee LS, Ye YT, Khee TC, Nie LZ, Yee NJ, et al.
    Diabetes Res Clin Pract, 2017 Oct;132:157-168.
    PMID: 28797524 DOI: 10.1016/j.diabres.2017.07.025
    BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a chronic disorder and its treatment with only metformin often does not provide optimum glycemic control. Addition of sodium glucose cotransporter 2 inhibitor (SGLT2) will improve the glycemic control in patients on metformin alone. In this study, an attempt is made to investigate the combined therapy of SGLT-2 with metformin in managing T2DM in terms of lowering HbA1c and body weight and monotherapy using metformin alone in HbA1c and body weight reduction.

    OBJECTIVES: To compare the clinical effectiveness of combined therapy using SGLT2 inhibitor and metformin with monotherapy using metformin alone in HbA1c and body weight reduction.

    METHOD: A systematic review of the randomized controlled trials has been carried out and Cochrane risk of bias tool was used for the quality assessment. Patient, Intervention, Comparison and Outcomes (PICO) technique is used to select the relevant articles to meet the objective.

    RESULTS: The studies used in this article are multicenter, double-blinded randomized controlled trials on SGLT2 inhibitors with methformin, there were a total of 3897 participants, with a range of 182 to 1186 individual study size were included. Studies showed that combined therapy were more effective in HbA1c and body weight reduction as compared to monotherapy.

    CONCLUSION: The combined therapy of SGLT2 inhibitor along with metformin is more effective in HbA1c reduction and weight reduction as compared to monotherapy using metformin alone. Among the three SGLT2 inhibitors such as dapagliflozin canagliflozin and empagliflozin do not differ much in the efficiency of weight reduction. However, Empagliflozin 25mg is effective in HbA1c reduction.

  20. Enhancing biopharmaceutical performance of an anticancer drug by long chain PUFA based self-nanoemulsifying lipidic nanomicellar systems
    Khurana RK, Beg S, Burrow AJ, Vashishta RK, Katare OP, Kaur S, et al.
    Eur J Pharm Biopharm, 2017 Dec;121:42-60.
    PMID: 28887099 DOI: 10.1016/j.ejpb.2017.09.001
    The aim of this study was to develop polyunsaturated fatty acid (PUFA) long chain glyceride (LCG) enriched self-nanoemulsifying lipidic nanomicelles systems (SNELS) for augmenting lymphatic uptake and enhancing oral bioavailability of docetaxel and compare its biopharmaceutical performance with a medium-chain fatty acid glyceride (MCG) SNELS. Equilibrium solubility and pseudo ternary phase studies facilitated the selection of suitable LCG and MCG. The critical material attributes (CMAs) and critical process parameters (CPPs) were earmarked using Placket-Burman Design (PBD) and Fractional Factorial Design (FFD) for LCG- and MCG-SNELS respectively, and nano micelles were subsequently optimized using I- and D-optimal designs. Desirability function unearthed the optimized SNELS with Temul <5min, Dnm <100nm, Rel15min >85% and Perm45min >75%. The SNELS demonstrated efficient biocompatibility and energy dependent cellular uptake, reduced P-gp efflux and increased permeability using bi-directional Caco-2 model. Optimal PUFA enriched LCG-SNELS exhibited distinctly superior permeability and absorption parameters during ex vivo permeation, in situ single pass intestinal perfusion, lymphatic uptake and in vivo pharmacokinetic studies over MCG-SNELS.
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