Displaying publications 21 - 40 of 74 in total

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  1. Nordin N, Yeap SK, Rahman HS, Zamberi NR, Abu N, Mohamad NE, et al.
    Sci Rep, 2019 02 07;9(1):1614.
    PMID: 30733560 DOI: 10.1038/s41598-018-38214-x
    Very recently, we postulated that the incorporation of citral into nanostructured lipid carrier (NLC-Citral) improves solubility and delivery of the citral without toxic effects in vivo. Thus, the objective of this study is to evaluate anti-cancer effects of NLC-Citral in MDA MB-231 cells in vitro through the Annexin V, cell cycle, JC-1 and fluorometric assays. Additionally, this study is aimed to effects of NLC-Citral in reducing the tumor weight and size in 4T1 induced murine breast cancer model. Results showed that NLC-Citral induced apoptosis and G2/M arrest in MDA MB-231 cells. Furthermore, a prominent anti-metastatic ability of NLC-Citral was demonstrated in vitro using scratch, migration and invasion assays. A significant reduction of migrated and invaded cells was observed in the NLC-Citral treated MDA MB-231 cells. To further evaluate the apoptotic and anti-metastatic mechanism of NLC-Citral at the molecular level, microarray-based gene expression and proteomic profiling were conducted. Based on the result obtained, NLC-Citral was found to regulate several important signaling pathways related to cancer development such as apoptosis, cell cycle, and metastasis signaling pathways. Additionally, gene expression analysis was validated through the targeted RNA sequencing and real-time polymerase chain reaction. In conclusion, the NLC-Citral inhibited the proliferation of breast cancer cells in vitro, majorly through the induction of apoptosis, anti-metastasis, anti-angiogenesis potentials, and reducing the tumor weight and size without altering the therapeutic effects of citral.
    Matched MeSH terms: Lipids/chemistry*
  2. Siram K, Divakar S, Raghavan CV, Marslin G, Rahman H, Franklin G
    Colloids Surf B Biointerfaces, 2019 Feb 01;174:443-450.
    PMID: 30497005 DOI: 10.1016/j.colsurfb.2018.11.033
    The physico-chemical properties of lipids influencing the solubilisation of imatinib mesylate (IM) in lipid matrix were evaluated and a statistical model to predict the same has been derived in the present study. After experimental quantification of IM solubility in various lipids, Hansen Hildebrand's total solubility parameters were calculated in order to study the role of various forces connected to lipid-drug interaction. To develop a relationship between the various descriptors of the lipids and experimental solubility of IM in lipids (% w/w), quantitative structure-solubility relationship (QSSR) was used. To generate equations that can predict the solubility of IM in lipids (%w/w), multiple linear regression was used. Amongst the various lipids tested, glyceryl monostearate and behenic acid solubilised the highest (6.19 ± 0.22%) and lowest (0.01 ± 0.01%) amounts of IM respectively. Our results suggested that alkyl chain length, polarity of the lipids, index of cohesive interaction in solids, estimated number of hydrogen bonds that would be accepted by the solute from water molecules in an aqueous solution, estimated number of hydrogen bonds that would be donated by the solute to water molecules in an aqueous solution and solvent accessible surface area collectively play a significant role in solubilising IM in the lipids. The equation developed could predict the solubility of IM in lipids with good accuracy (R2pred = 0.912).
    Matched MeSH terms: Lipids/chemistry*
  3. Lian W, Wang W, Tan CP, Wang J, Wang Y
    Bioprocess Biosyst Eng, 2019 Feb;42(2):321-329.
    PMID: 30421172 DOI: 10.1007/s00449-018-2036-7
    LML-type structured lipids are one type of medium- and long-chain triacylglycerols. LML was synthesized using immobilized Talaromyces thermophilus lipase (TTL)-catalyzed interesterification of tricaprylin and ethyl linoleate. The resin AB-8 was chosen, and the lipase/support ratio was determined to be 60 mg/g. Subsequently, the immobilized TTL with strict sn-1,3 regiospecificity was applied to synthesize LML. Under the optimized conditions (60 °C, reaction time 6 h, enzyme loading of 6% of the total weight of substrates, substrate of molar ratio of ethyl linoleate to tricaprylin of 6:1), Triacylglycerols with two long- and one medium-chain FAs (DL-TAG) content as high as 52.86 mol% was obtained. Scale-up reaction further verified the industrial potential of the established process. The final product contained 85.24 mol% DL-TAG of which 97 mol% was LML after purification. The final product obtained with the high LML content would have substantial potential to be used as functional oils.
    Matched MeSH terms: Lipids/chemistry*
  4. Beh CY, Rasedee A, Selvarajah GT, Yazan LS, Omar AR, Foong JN, et al.
    PLoS One, 2019;14(7):e0219285.
    PMID: 31291309 DOI: 10.1371/journal.pone.0219285
    Nanomedicine is an emerging area in the medical field, particularly in the treatment of cancers. Nanostructured lipid carrier (NLC) was shown to be a good nanoparticulated carrier for the delivery of tamoxifen (TAM). In this study, the tamoxifen-loaded erythropoietin-coated nanostructured lipid carriers (EPO-TAMNLC) were developed to enhance the anti-cancer properties and targetability of TAM, using EPO as the homing ligand for EPO receptors (EpoRs) on breast cancer tissue cells. Tamoxifen-loaded NLC (TAMNLC) was used for comparison. The LA7 cells and LA7 cell-induced rat mammary gland tumor were used as models in the study. Immunocytochemistry staining showed that LA7 cells express estrogen receptors (ERs) and EpoRs. EPO-TAMNLC and TAMNLC significantly (p<0.05) inhibited proliferation of LA7 in dose- and time-dependent manner. EPO-TAMNLC induced apoptosis and G0/G1 cell cycle arrest of LA7 cells. Both drug delivery systems showed anti-mammary gland tumor properties. At an intravenous dose of 5 mg kg-1 body weight, EPO-TAMNLC and TAMNLC were not toxic to rats, suggesting that both are safe therapeutic compounds. In conclusion, EPO-TAMNLC is not only a unique drug delivery system because of the dual drug-loading feature, but also potentially highly specific in the targeting of breast cancer tissues positive for ERs and EpoRs. The incorporation of TAM into NLC with and without EPO coat had significantly (p<0.05) improved specificity and safety of the drug carriers in the treatment of mammary gland tumors.
    Matched MeSH terms: Lipids/chemistry
  5. Dua K, Awasthi R, Madan JR, Chellappan DK, Nalluri BN, Gupta G, et al.
    Panminerva Med, 2018 Dec;60(4):238-240.
    PMID: 29480673 DOI: 10.23736/S0031-0808.18.03428-6
    Matched MeSH terms: Lipids/chemistry
  6. Ngan CL, Asmawi AA
    Drug Deliv Transl Res, 2018 10;8(5):1527-1544.
    PMID: 29881970 DOI: 10.1007/s13346-018-0550-4
    Inhalation therapy of lipid-based carriers has great potential in direct target towards the root of respiratory diseases, which make them superior over other drug deliveries. With the successful entry of lipid carriers into the target cells, drugs can be absorbed in a sustained release manner and yield extended medicinal effects. Nevertheless, translation of inhalation therapy from laboratory to clinic especially in drug delivery remains a key challenge to the formulators. An ideal drug vehicle should safeguard the drugs from any premature elimination, facilitate cellular uptake, and promote maximum drug absorption with negligible toxicity. Despite knowing that lung treatment can be done via systemic delivery, pulmonary administration is capable of enhancing drug retention within the lungs, while minimizing systemic toxicity with local targeting. Current inhalation therapy of lipid-based carriers can be administered either intratracheally or intranasally to reach deep lung. However, the complex dimensions of lung architectural and natural defense mechanism poise major barriers towards targeted pulmonary delivery. Delivery systems have to be engineered in a way to tackle various diseases according to their biological conditions. This review highlights on the developmental considerations of lipid-based delivery systems cater for the pulmonary intervention of different lung illnesses.
    Matched MeSH terms: Lipids/chemistry
  7. Gupta G, Singhvi G, Chellappan DK, Sharma S, Mishra A, Dahiya R, et al.
    Panminerva Med, 2018 Sep;60(3):109-116.
    PMID: 30176701 DOI: 10.23736/S0031-0808.18.03462-6
    Glioblastoma, also known as glioblastoma multiforme, is the most common and worldwide-spread cancer that begins within the brain. Glioblastomas represent 15% of brain tumors. The most common length of survival following diagnosis is 12 to 14 months with less than 3% to 5% of people surviving longer than five years. Without treatment, survival is typically 3 months. Among all receptors, special attention has been focused on the role of peroxisome proliferator-activated receptors (PPARs) in glioblastoma. PPARs are ligand-activated intracellular transcription factors. The PPAR subfamily consists of three subtypes encoded by distinct genes named PPARα, PPARβ/δ, and PPARγ. PPARγ is the most extensively studied subtype of PPAR. There has been interesting preliminary evidence suggesting that diabetic patients receiving PPARγ agonists, a group of anti-diabetics, thiazolidinedione drugs, have an increased median survival for glioblastoma. In this paper, the recent progresses in understanding the potential mechanism of PPARγ in glioblastoma are summarized.
    Matched MeSH terms: Lipids/chemistry
  8. Ong YS, Saiful Yazan L, Ng WK, Abdullah R, Mustapha NM, Sapuan S, et al.
    Nanomedicine (Lond), 2018 07;13(13):1567-1582.
    PMID: 30028248 DOI: 10.2217/nnm-2017-0322
    AIM: To investigate the enhancement of anticancer activity of thymoquinone (TQ) by the use of nanostructured lipid carrier (NLC) in 4T1 tumor-bearing female BALB/c mice.

    MATERIAL & METHODS: TQ was incorporated into NLC (TQNLC) by using high pressure homogenization. TQNLC and TQ were orally administered to the mice.

    RESULTS & CONCLUSION: TQNLC and TQ are potential chemotherapeutic drugs as they exhibited anticancer activity. The use of NLC as a carrier has enhanced the therapeutic property of TQ by increasing the survival rate of mice. The antimetastasis effect of TQNLC and TQ to the lungs was evidence by downregulation of MMP-2. TQNLC and TQ induced apoptosis via modulation of Bcl-2 and caspase-8 in the intrinsic apoptotic pathway.

    Matched MeSH terms: Lipids/chemistry
  9. Karim A, Yousuf A, Islam MA, Naif YH, Faizal CKM, Alam MZ, et al.
    Biotechnol Prog, 2018 07;34(4):838-845.
    PMID: 29464927 DOI: 10.1002/btpr.2625
    The aim of the study was to investigate the feasibility of using irreversible electroporation (EP) as a microbial cell disruption technique to extract intracellular lipid within short time and in an eco-friendly manner. An EP circuit was designed and fabricated to obtain 4 kV with frequency of 100 Hz of square waves. The yeast cells of Lipomyces starkeyi (L. starkeyi) were treated by EP for 2-10 min where the distance between electrodes was maintained at 2, 4, and 6 cm. Colony forming units (CFU) were counted to observe the cell viability under the high voltage electric field. The forces of the pulsing electric field caused significant damage to the cell wall of L. starkeyi and the disruption of microbial cells was visualized by field emission scanning electron microscopic (FESEM) image. After breaking the cell wall, lipid was extracted and measured to assess the efficiency of EP over other techniques. The extent of cell inactivation was up to 95% when the electrodes were placed at the distance of 2 cm, which provided high treatment intensity (36.7 kWh m-3 ). At this condition, maximum lipid (63 mg g-1 ) was extracted when the biomass was treated for 10 min. During the comparison, EP could extract 31.88% lipid while the amount was 11.89% for ultrasonic and 16.8% for Fenton's reagent. The results recommend that the EP is a promising technique for lowering the time and solvent usage for lipid extraction from microbial biomass. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 34:838-845, 2018.
    Matched MeSH terms: Lipids/chemistry
  10. Kundu SK, Chakraborty C, Yagihara S, Teoh SL, Das S
    Curr Drug Deliv, 2018;15(10):1381-1392.
    PMID: 30124152 DOI: 10.2174/1567201815666180820101255
    Surgical operations are impossible without administering proper analgesia. Advancement in the field of anesthesia has invariably resulted in the accomplishment of all surgical processes without any inconvenience. Admittedly, the use of noble gas is on the decline. The noble gases may not interact chemically with any other substance under normal temperature and pressure but they may interact with proteins and lipids. Different anesthetic molecules may stimulate either proteins or lipids in membrane. There is a connection between the anesthetic molecules and the hydrophobic region of the membrane. In the present review, we attempt to highlight the interaction between the anesthetic molecule with proteins and lipids and their effects. We sketched few noble gases and some other existing molecules such as halothane and alcohol which interacted with proteins and lipids.
    Matched MeSH terms: Lipids/chemistry*
  11. 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.
    Matched MeSH terms: Lipids/chemistry*
  12. Azman NA, Skowyra M, Muhammad K, Gallego MG, Almajano MP
    Pharm Biol, 2017 Dec;55(1):912-919.
    PMID: 28152668 DOI: 10.1080/13880209.2017.1282528
    CONTEXT: Betula pendula Roth (Betulaceae) exhibits many pharmacological activities in humans including anticancer, antibacterial, and antiviral effects. However, the antioxidant activity of BP towards lipid degradation has not been fully determined.

    OBJECTIVE: The BP ethanol and methanol extracts were evaluated to determine antioxidant activity by an in vitro method and lyophilized extract of BP was added to beef patties to study oxidative stability.

    MATERIALS AND METHODS: Antioxidant activities of extracts of BP were determined by measuring scavenging radical activity against methoxy radical generated by Fenton reaction 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (TEAC) radical cation, the oxygen radical absorbance capacity (ORAC) and the ferric reducing antioxidant power (FRAP) assays. The lipid deterioration in beef patties containing 0.1% and 0.3% (w/w) of lyophilized extract of BP stored in 80:20 (v/v) O2:CO2 modified atmosphere (MAP) at 4 °C for 10 days was determined using thiobarbituric acid reacting substances (TBARS), % metmyoglobin and colour value.

    RESULTS: The BP methanol extract revealed the presence of catechin, myricetin, quercetin, naringenin, and p-coumaric acid. The BP ethanol (50% w/w) extract showed scavenging activity in TEAC, ORAC and FRAP assays with values of 1.45, 2.81, 1.52 mmol Trolox equivalents (TE)/g DW, respectively. Reductions in lipid oxidation were found in samples treated with lyophilized BP extract (0.1% and 0.3% w/w) as manifested by the changes of colour and metmyoglobin concentration. A preliminary study film with BP showed retard degradation of lipid in muscle food.

    CONCLUSION: The present results indicated that the BP extracts can be used as natural food antioxidants.

    Matched MeSH terms: Lipids/chemistry
  13. Noor NM, Sheikh K, Somavarapu S, Taylor KMG
    Eur J Pharm Biopharm, 2017 Aug;117:372-384.
    PMID: 28412472 DOI: 10.1016/j.ejpb.2017.04.012
    Dutasteride, used for treating benign prostate hyperplasia (BPH), promotes hair growth. To enhance delivery to the hair follicles and reduce systemic effects, in this study dutasteride has been formulated for topical application, in a nanostructured lipid carrier (NLC) coated with chitosan oligomer-stearic acid (CSO-SA). CSO-SA has been successfully synthesized, as confirmed using1H NMR and FTIR. Formulation of dutasteride-loaded nanostructured lipid carriers (DST-NLCs) was optimized using a 23full factorial design. This formulation was coated with different concentrations of stearic acid-chitosan solution. Coating DST-NLCs with 5% SA-CSO increased mean size from 187.6±7.0nm to 220.1±11.9nm, and modified surface charge, with zeta potentials being -18.3±0.9mV and +25.8±1.1mV for uncoated and coated DST-NLCs respectively. Transmission electron microscopy showed all formulations comprised approximately spherical particles. DST-NLCs, coated and uncoated with CSO-SA, exhibited particle size stability over 60days, when stored at 4-8°C. However, NLCs coated with CSO (without conjugation) showed aggregation when stored at 4-8°C after 30days. The measured particle size for all formulations stored at 25°C suggested aggregation, which was greatest for DST-NLCs coated with 10% CSO-SA and 5% CSO. All nanoparticle formulations exhibited rapid release in an in vitro release study, with uncoated NLCs exhibiting the fastest release rate. Using a Franz diffusion cell, no dutasteride permeated through pig ear skin after 48h, such that it was not detected in the receptor chamber for all samples. The amount of dutasteride in the skin was significantly different (p<0.05) for DST-NLCs (6.09±1.09μg/cm2) without coating and those coated with 5% CSO-SA (2.82±0.40μg/cm2), 10% CSO-SA (2.70±0.35μg/cm2) and CSO (2.11±0.64μg/cm2). There was a significant difference (p<0.05) in the cytotoxicity (IC50) between dutasteride alone and in the nanoparticles. DST-NLCs coated and uncoated with CSO-SA increased the maximum non-toxic concentration by 20-fold compared to dutasteride alone. These studies indicate that a stearic acid-chitosan conjugate was successfully prepared, and modified the surface charge of DST-NLCs from negative to positive. These stable, less cytotoxic, positively-charged dutasteride-loaded nanostructured lipid carriers, with stearic acid-chitosan oligomer conjugate, are appropriate for topical delivery and have potential for promotion of hair growth.
    Matched MeSH terms: Lipids/chemistry*
  14. 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.

    Matched MeSH terms: Lipids/chemistry
  15. Sengupta P, Chatterjee B
    Int J Pharm, 2017 Jun 30;526(1-2):353-365.
    PMID: 28461261 DOI: 10.1016/j.ijpharm.2017.04.068
    The Nanoemulgel drug delivery system is a formulation related intervention to improve the systemic delivery and therapeutic profile of lipophilic drugs. Nanoemulgel is an amalgamated formulation of two different systems in which nanoemulsion containing drug is incorporated into a gel base. The fusion of the two systems makes this formulation advantageous in several ways. Lipophilic drugs can be easily incorporated and the skin permeability of the incorporated drugs can be enhanced in several folds due to the finely distributed droplets of nanoemulsion phase. As a result, the pharmacokinetic and pharmacodynamic profiles of the lipophilic drugs are improved significantly. An increasing trend in topical nanoemulgel use in recent years has been noticed because of the better acceptability of the preparation to the patients due to their noninvasive delivery, avoidance of gastrointestinal side effects, easier applicability and good therapeutic and safety profile. Despite of having few limitations, nanoemulgel formulation can be considered as a potential and promising candidates for topical delivery of lipophilic drugs in the future. The aim of this review is to evaluate and report the current potential and future scope of nanoemulgel formulation for becoming an effective delivery system for poorly water soluble drugs. In this review, we have summarized and discussed the outcome of different studies on permeability, pharmacokinetic, pharmacodynamic and safety profile of the drugs delivered topically through nanoemulgel. Rationality of use along with the major challenges to overcome for nanoemulgel formulation has been discussed.
    Matched MeSH terms: Lipids/chemistry
  16. Hussain Z, Thu HE, Ng SF, Khan S, Katas H
    Colloids Surf B Biointerfaces, 2017 Feb 01;150:223-241.
    PMID: 27918967 DOI: 10.1016/j.colsurfb.2016.11.036
    Wound healing is a multifarious and vibrant process of replacing devitalized and damaged cellular structures, leading to restoration of the skin's barrier function, re-establishment of tissue integrity, and maintenance of the internal homeostasis. Curcumin (CUR) and its analogs have gained widespread recognition due to their remarkable anti-inflammatory, anti-infective, anticancer, immunomodulatory, antioxidant, and wound healing activities. However, their pharmaceutical significance is limited due to inherent hydrophobic nature, poor water solubility, low bioavailability, chemical instability, rapid metabolism and short half-life. Owing to their pharmaceutical limitations, newer strategies have been attempted in recent years aiming to mitigate problems related to the effective delivery of curcumanoids and to improve their wound healing potential. These advanced strategies include nanovesicles, polymeric micelles, conventional liposomes and hyalurosomes, nanocomposite hydrogels, electrospun nanofibers, nanohybrid scaffolds, nanoconjugates, nanostructured lipid carriers (NLCs), nanoemulsion, nanodispersion, and polymeric nanoparticles (NPs). The superior wound healing activities achieved after nanoencapsulation of the CUR are attributed to its target-specific delivery, longer retention at the target site, avoiding premature degradation of the encapsulated cargo and the therapeutic superiority of the advanced delivery systems over the conventional delivery. We have critically reviewed the literature and summarize the convincing evidence which explore the pharmaceutical significance and therapeutic feasibility of the advanced delivery systems in improving wound healing activities of the CUR and its analogs.
    Matched MeSH terms: Lipids/chemistry
  17. Amekyeh H, Billa N, Roberts C
    Int J Pharm, 2017 Jan 30;517(1-2):42-49.
    PMID: 27923696 DOI: 10.1016/j.ijpharm.2016.12.001
    Oral delivery of pharmaceuticals requires that they retain their physical and chemical attributes during transit within the gastrointestinal (GI) tract, for the manifestation of desired therapeutic profiles. Solid lipid nanoparticles (SLNs) are used as carriers to improve the absorption of hydrophobic drugs. In this study, we examine the stability of amphotericin B (AmB) and paracetamol (PAR) SLNs in simulated GI fluids during gastric emptying. On contact with the simulated fluids, the particles increased in size due to ingress of the dissolution media into the particles. Simulated gastric emptying revealed that the formulations had mean sizes <350nm and neutral surface charges, both of which are optimal for intestinal absorption of SLNs. There was ingress of the fluids into the SLNs, followed by diffusion of the dissolved drug, whose rate depended on the solubility of the loaded-drug in the particular medium. Time-of-flight secondary ion mass spectrometry analyses indicated that drug loading followed the core-shell model and that the AmB SLNs have a more drug-enriched core than the PAR SLNs do. The AmB SLNs are therefore a very suitable carrier of AmB for oral delivery. The stability of the SLNs in the simulated GI media indicates their suitability for oral delivery.
    Matched MeSH terms: Lipids/chemistry*
  18. Beh CY, How CW, Foo JB, Foong JN, Selvarajah GT, Rasedee A
    Drug Des Devel Ther, 2017;11:771-782.
    PMID: 28352153 DOI: 10.2147/DDDT.S123939
    Tamoxifen (TAM) has been used in the treatment of breast cancers and is supplemented with erythropoietin (EPO) to alleviate the cancer-related anemia. The purported deleterious effects caused by the use of EPO with chemotherapeutic agents in the treatment of cancer-related anemia vary across studies and remain controversial. The use of nanoparticles as a drug delivery system has the potential to improve the specificity of anticancer drugs. In this study, we simultaneously incorporated two pharmacological active ingredients in one nanocarrier to develop EPO-conjugated TAM-loaded lipid nanoparticles (EPO-TAMNLC), a targeted delivery system, to enhance the cytotoxic activity while reducing the side effects of the ingredients. The effect of temperature in modulating the thermodynamic parameters associated with the binding of EPO and TAMNLC was assessed using isothermal titration calorimetry, while the unfolding of EPO structure was determined using fluorescence-quenching approach. The association efficiency of EPO and TAMNLC was 55.43%. Unlike binding of albumin to TAMNLC, the binding of EPO to TAMNLC occurred through endothermic and entropy-driven reaction. The EPO-TAMNLC formulation was stable because of the hydrophobic interaction and the high free energy, suggesting the spontaneity of the interactions between EPO and TAMNLC. The EPO-TAMNLC enhanced the in vitro cytotoxicity of TAM to MCF-7 cells. The EPO surface-functionalized TAMNLC could sequentially deliver EPO and TAM as well as improving site-specific delivery of these therapeutic compounds.
    Matched MeSH terms: Lipids/chemistry*
  19. Ong YS, Saiful Yazan L, Ng WK, Noordin MM, Sapuan S, Foo JB, et al.
    Int J Nanomedicine, 2016 11 09;11:5905-5915.
    PMID: 27877037
    BACKGROUND: Thymoquinone (TQ), the predominant active lipophilic component in Nigella sativa seed oil, has a variety of pharmacological properties such as anticancer activities. However, translation of TQ to clinical phase is still not possible due to its hydrophobic properties. This problem can be solved by encapsulating it in nanoformulations to enhance its pharmacological properties. In our previous study, TQ has been successfully encapsulated in a nanostructured lipid carrier (hereinafter referred to as TQNLC) with excellent physiochemical properties such as high encapsulation efficiency, high drug-loading capacity, particle diameter less than 100 nm, and stability up to 2 years. In vitro studies also proved that TQNLC exhibited antiproliferative activity toward breast and cervical cancer cell lines. However, no toxicity profile related to this formulation has been reported. In this study, we determine and compare the in vivo toxicity of both TQNLC and TQ.

    MATERIALS AND METHODS: The in vivo toxicity (acute and subacute toxicity) study was carried out by oral administration of TQNLC and TQ to BALB/c mice. Animal survival, body weight, organ weight-to-body weight ratio, hematological profile, biochemistry profile, and histopathological changes were analyzed.

    RESULTS: In acute toxicity, TQ that is loaded in nanostructured lipid carrier (NLC) was found to be less toxic than pure TQ. It can be concluded that encapsulation of TQ in lipid carrier minimizes the toxicity of the compound. In the subacute toxicity study, oral administration of 100 mg/kg of TQNLC and TQ did not cause mortality to either male or female but resulted in toxicity to the liver. It is postulated that long-term consumption of TQNLC and TQ may cause toxicity to the liver but not to the extent of altering the functions of the organ. For both treatments, the no observed adverse effect level (NOAEL) was found to be 10 mg/kg/d for mice in both sexes.

    CONCLUSION: For long-term oral consumption, TQ and TQNLC at a dose of 10 mg/kg is safe in mice and does not exert any toxic effect. The results provide safety information of TQNLC, which would further help researchers in clinical use.

    Matched MeSH terms: Lipids/chemistry*
  20. Soni N, Soni N, Pandey H, Maheshwari R, Kesharwani P, Tekade RK
    J Colloid Interface Sci, 2016 Nov 01;481:107-16.
    PMID: 27459173 DOI: 10.1016/j.jcis.2016.07.020
    Gemcitabine (GmcH) is an effective anti-cancer agent used in the chemotherapy of lung cancer. However, the clinical applications of GmcH has been impeded primarily due to its low blood residence time, unfavorable pharmacokinetic and pharmacodynamic (PK/PD) profile, and poor penetration in the complex environment of lung cancer cells. Thus, the present study aims to formulate GmcH loaded mannosylated solid lipid nanoparticles (GmcH-SLNs) for improving its drug uptake into the lung cancer cells. GmcH-SLNs were prepared by emulsification and solvent evaporation process, and surface modification was done with mannose using ring opening technique. The cellular toxicity and cell uptake studies were performed in A549 lung adenocarcinoma cell line. The developed nanoformulation appears to be proficient in targeted delivery of GmcH with improved therapeutic effectiveness and enhanced safety.
    Matched MeSH terms: Lipids/chemistry*
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