Displaying publications 1 - 20 of 48 in total

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  1. Wong TW
    Curr Drug Deliv, 2008 Apr;5(2):77-84.
    PMID: 18393808
    Microwave has received a widespread application in pharmaceuticals and food processing, microbial sterilization, biomedical therapy, scientific and biomedical analysis, as well as, drug synthesis. This paper reviews the basis of application of microwave to prepare pharmaceutical dosage forms such as agglomerates, gel beads, microspheres, nanomatrix, solid dispersion, tablets and film coat. The microwave could induce drying, polymeric crosslinkages as well as drug-polymer interaction, and modify the structure of drug crystallites via its effects of heating and/or electromagnetic field on the dosage forms. The use of microwave opens a new approach to control the physicochemical properties and drug delivery profiles of pharmaceutical dosage forms without the need for excessive heat, lengthy process or toxic reactants. Alternatively, the microwave can be utilized to process excipients prior to their use in the formulation of drug delivery systems. The intended release characteristics of drugs in dosage forms can be met through modifying the physicochemical properties of excipients using the microwave.
  2. Singh G, Kesharwani P, Srivastava AK
    Curr Drug Deliv, 2018;15(3):312-320.
    PMID: 29165080 DOI: 10.2174/1567201814666171120125916
    BACKGROUND: Tuberculosis is an infection and caused by gentle growing bacteria. The Internet provides opportunities for people with tuberculosis (TB) to connect with one another to address these challenges.

    OBJECTIVE: The aim of this paper is to introduce readers to the platforms on which Tuberculosis participants interact, to discuss reasons for and risks associated with TB-related activity, and to review research related to the potential impact of individual participation on TB outcomes.

    METHODS: Research and online content related to Tuberculosis online activity is reviewed, however, the difficulty in accurate prescribing and adhering to these protocols and the emergence of M. tuberculosis strains resistant to multiple drugs and drug-drug interactions that interfere with optimal treatment of Tuberculosis and co-infected patients with the different disease has generated a pressing need for improved Tuberculosis therapies.

    RESULTS: Together with the ominous global burden of Tuberculosis, those shortcomings of current medication have contributed to a renewed interest in the development of improved drugs and protocols for the medication of Tuberculosis. This article features obstacles related with the enhanced utilization of existing drugs and difficulties related with the advancement of enhanced products, concentrating on perspectives characteristic in Tuberculosis drug clinical improvement. The participation includes peer support, advocacy, self-expression, seeking and sharing TB information, improving approaches to Tuberculosis data management, and humour.

    CONCLUSION: This article highlights hurdles related to the optimised use of existing drugs and challenges related to the development of improved products, focusing on aspects inherent in Tuberculosis drug clinical development. Concluding comments offer processes for more efficient development of Tuberculosis therapies and increase the quality of life.

  3. AlMatar M, Makky EA, Var I, Koksal F
    Curr Drug Deliv, 2018;15(4):470-484.
    PMID: 29219055 DOI: 10.2174/1567201815666171207163504
    BACKGROUND: Until recently, one of the main reasons for mortality has been infectious diseases, and bacteria that are drug-resistant have emerged as a result of the wide application, as well as the misuse of antibacterial medications. Having multidrug-resistance, bacteria present a great problem for the efficient management of bacterial infections and this challenge has resulted in the creation of other means of dealing with bacterial diseases. Of late, metallic nanoparticles (NPs), employed as antibacterial agents, have the potential for use against resistance to bacterial drugs.

    OBJECTIVE: The mechanisms of bacterial resistance are described in this review and this is followed by an outline of the features and uses of metallic NPs as antibiotic agents to address bacteria that are antibiotic- sensitive and resistant. Additionally, a general impression of metallic NPs as antibiofilm bactericidal agents is presented.

    CONCLUSION: Biofilms and bacterial strains that are resistant to antibiotics present a grave public health challenge and this has enhanced the need to develop new bactericidal agents. Therefore, nanomaterials are considered as a potential platform for managing bacterial infections.

  4. Masadeh MM, Bany-Ali NM, Khanfar MS, Alzoubi KH, Massadeh MM, Almomani EM
    Curr Drug Deliv, 2024 Jan 12.
    PMID: 38231065 DOI: 10.2174/0115672018279213240110045557
    BACKGROUND: The misuse of antibiotics leads to a global increase in antibiotic resistance. Therefore, it is imperative to search for alternative compounds to conventional antibiotics. ZnO nanoparticles (Zn NP) are one of these alternatives because they are an effective option to overcome biofilm bacterial cells and a novel way to overcome multidrug resistance in bacteria. The current research study aims to characterize the efficacy of ZnO nanoparticles alone and in combination with other antibacterial drugs against bacterial biofilms.

    METHODS: ZnO NPs were prepared by co-precipitation method, and their anti-biofilm and antibacterial activities alone or combined with four types of broad-spectrum antibacterial (Norfloxacin, Colistin, Doxycycline, and Ampicillin) were evaluated against E. coli and S. aureus bacterial strains. Finally, the cytotoxicity and the hemolytic activity were evaluated.

    RESULTS: ZnO NPs were prepared, and results showed that their size was around 10 nm with a spherical shape and a zeta potential of -21.9. In addition, ZnO NPs were found to have a strong antibacterial effect against Gram-positive and Gram-negative microorganisms, with a minimum inhibitory concentration (MIC) of 62.5 and 125 μg/mL, respectively. Additionally, they could eradicate biofilmforming microorganisms at a concentration of 125 μg/m. ZnO NPs were found to be non-toxic to erythrocyte cells. Still, some toxicity was observed for Vero cells at effective concentration ranges needed to inhibit bacterial growth and eradicate biofilm-forming organisms. When combined with different antibacterial, ZnO NP demonstrated synergistic and additive effects with colistin, and the MIC and MBEC of the combination decreased significantly to 0.976 μg/mL against planktonic and biofilm strains of MDR Gram-positive bacteria, resulting in significantly reduced toxicity.

    CONCLUSION: The findings of this study encourage the development of alternative therapies with high efficacy and low toxicity. ZnO nanoparticles have demonstrated promising results in overcoming multi-drug resistant bacteria and biofilms, and their combination with colistin has shown a significant reduction in toxicity. Further studies are needed to investigate the potential of ZnO nanoparticles as a viable alternative to conventional antibiotics.

  5. Rehman U, Sarfraz RM, Mahmood A, Hussain Z, Thu HE, Zafar N, et al.
    Curr Drug Deliv, 2021 Feb 11.
    PMID: 33583374 DOI: 10.2174/1567201818666210212085912
    BACKGROUND: Despite exhibiting promising anticancer potential, the clinical significance of capecitabine (a potent prodrug of 5-fluorouracil used for treatment of colorectal cancer) is limited owing to its acidic and enzymatic hydrolysis, lower absorption following the oral administration, poor bioavailability, short plasma half-life and poor patient compliance.

    OBJECTIVES: The present study was aimed to fabricate the capecitabine as smart pH-responsive hydrogel network to efficiently facilitate its oral delivery while shielding its stability in the gastric media.

    METHODS: The smart pH sensitive HP-β-CD/agarose-g-poly(MAA) hydrogel network was developed using an aqueous free radical polymerization technique. The developed hydrogels were characterized for drug-loading efficiency, structural and compositional features, thermal stability, swelling behaviour, morphology, physical form, and release kinetics. The pH-responsive behaviour of developed hydrogels was established by conducting the swelling and release behaviour at different pH values (1.2 and 7.4), demonstrating significantly higher swelling and release at pH 7.4 as compared with pH 1.2. The capecitabine-loaded hydrogels were also screened for acute oral toxicity in animals by analysing the body weight, water and food intake, dermal toxicity, ocular toxicity, biochemical analysis, and histological examination.

    RESULTS: The characteristic evaluations revealed that capecitabine (anticancer agent) was successfully loaded into the hydrogel network. Capecitabine loading was ranged from 71.22% to 90.12%. An interesting feature of hydrogel was its pH-responsive behaviour which triggers release at basic pH (94.25%). Optimum swelling (95%) was seen at pH 7.4. Based upon regression coefficient R2 (0.96 - 0.99) best fit model was zero order. The extensive toxicity evaluations evidenced good safety profile with no signs of oral, dermal or ocular toxicities, as well as no variations in blood parameters and histology of vital organs.

    CONCLUSION: Our findings conclusively evinced that the developed hydrogel exhibited excellent pharmaceutical and therapeutic potential and thus can be employed as pH-responsive system for controlled delivery of anticancer agents.

  6. Tufail S, Siddique MI, Sarfraz M, Sohail MF, Shahid MN, Omer MO, et al.
    Curr Drug Deliv, 2021 Jul 20.
    PMID: 34288836 DOI: 10.2174/1567201818666210720150929
    INTRODUCTION: The pleiotropic effects of statins are recently explored for wound healing through angiogenesis and lymph-angiogenesis that could be of great importance in diabetic wounds.

    AIM: Aim of the present study is to fabricate nanofilm embedded with simvastatin loaded chitosan nanoparticles (CS-SIM-NPs) has been reported herein to explore the efficacy of SIM in diabetic wound healing.

    METHODS: The NPs, prepared via ionic gelation, were 173nm ± 2.645 in size with a zeta potential -0.299 ± 0.009 and PDI 0.051 ± 0.088 with excellent encapsulation efficiency (99.97%). The optimized formulation (CS: TPP, 1:1) that exhibited the highest drug release (91.64%) was incorporated into polymeric nanofilm (HPMC, Sodium alginate, PVA), followed by in vitro characterization. The optimized nanofilm was applied to the wound created on the back of diabetes-induced (with alloxan injection 120 mg/kg) albino rats.

    RESULTS: The results showed significant (p < 0.05) improvement in the wound healing process compared to the diabetes-induced non-treated group. The results highlighted the importance of nanofilms loaded with SIM-NPs in diabetic wound healing through angiogenesis promotion at the wound site.

    CONCLUSION: Thus, CS-SIM-NPs loaded polymeric nanofilms could be an emerging diabetic wound healing agent in the industry of nanomedicines.

  7. Sharma V, Singh A, Chauhan S, Sharma PK, Chaudhary S, Sharma A, et al.
    Curr Drug Deliv, 2023 Sep 05.
    PMID: 37670704 DOI: 10.2174/1567201821666230905090621
    Drug discovery and development (DDD) is a highly complex process that necessitates precise monitoring and extensive data analysis at each stage. Furthermore, the DDD process is both time-consuming and costly. To tackle these concerns, artificial intelligence (AI) technology can be used, which facilitates rapid and precise analysis of extensive datasets within a limited timeframe. The pathophysiology of cancer disease is complicated and requires extensive research for novel drug discovery and development. The first stage in the process of drug discovery and development involves identifying targets. Cell structure and molecular functioning are complex due to the vast number of molecules that function constantly, performing various roles. Furthermore, scientists are continually discovering novel cellular mechanisms and molecules, expanding the range of potential targets. Accurately identifying the correct target is a crucial step in the preparation of a treatment strategy. Various forms of AI, such as machine learning, neural-based learning, deep learning, and network-based learning, are currently being utilised in applications, online services, and databases. These technologies facilitate the identification and validation of targets, ultimately contributing to the success of projects. This review focuses on the different types and subcategories of AI databases utilised in the field of drug discovery and target identification for cancer.
  8. Lokesh, Gulati N, Saini A, Singh S, Gupta G, MacLoughlin R, et al.
    Curr Drug Deliv, 2024 Mar 05.
    PMID: 38445696 DOI: 10.2174/0115672018289883240226113353
    Chronic Obstructive Pulmonary Disease (COPD), a chronic lung disease that causes breathing difficulties and obstructs airflow from the lungs, has a significant global health burden and affects millions of people worldwide. The use of pharmaceuticals in COPD treatment is aimed to alleviate symptoms, improve lung function, prevent exacerbations, and enhance the overall quality of life for patients. Nanotechnology holds great promise to alleviate the burden of COPD. The main goal of this review is to present the full spectrum of therapeutics based on nanostructures for the treatment and management of COPD, including nanoparticles, polymeric nanoparticles, polymeric micelles, solid-lipid nanoparticles, liposomes, exosomes, nanoemulsions, nanosuspensions, and niosomes. Nanotechnology is just one of the many areas of research that may contribute to the development of more effective and personalized treatment modalities for COPD patients in the future. Future studies may be focused on enhancing the therapeutic effectiveness of nanocarriers by conducting extensive mechanistic investigations to translate current scientific knowledge for the effective management of COPD with little or no adverse effects.
  9. Haque ST, Chowdhury EH
    Curr Drug Deliv, 2018;15(4):485-496.
    PMID: 29165073 DOI: 10.2174/1567201814666171120114034
    BACKGROUND: Delivery of conventional small molecule drugs and currently evolving nucleic acid-based therapeutics, such as small interfering RNAs (siRNAs) and genes, and contrast agents for high resolution imaging, to the target site of action is highly demanding to increase the therapeutic and imaging efficacy while minimizing the off-target effects of the delivered molecules, as well as develop novel therapeutic and imaging approaches.

    METHODS: We have undertaken a structured search for peer-reviewed research and review articles predominantly indexed in PubMed focusing on the organic-inorganic hybrid nanoparticles with evidence of their potent roles in intracellular delivery of therapeutic and imaging agents in different animal models.

    RESULTS: Organic-inorganic hybrid nanoparticles offer a number of advantages by combining the unique properties of the organic and inorganic counterparts, thus improving the pharmacokinetic behavior and targetability of drugs and contrast agents, and conferring the exclusive optical and magnetic properties for both therapeutic and imaging purposes. Different polymers, lipids, dendrimers, peptides, cell membranes, and small organic molecules are attached via covalent or non-covalent interactions with diverse inorganic nanoparticles of gold, mesoporous silica, magnetic iron oxide, carbon nanotubes and quantum dots for efficient drug delivery and imaging purposes.

    CONCLUSION: We have thus highlighted here the progress made so far in utilizing different organicinorganic hybrid nanoparticles for in vivo delivery of anti-cancer drugs, siRNA, genes and imaging agents.

  10. Varma LT, Singh N, Gorain B, Choudhury H, Tambuwala MM, Kesharwani P, et al.
    Curr Drug Deliv, 2020;17(4):279-291.
    PMID: 32039683 DOI: 10.2174/1567201817666200210122340
    The collection of different bulk materials forms the nanoparticles, where the properties of the nanoparticle are solely different from the individual components before being ensembled. Selfassembled nanoparticles are basically a group of complex functional units that are formed by gathering the individual bulk components of the system. It includes micelles, polymeric nanoparticle, carbon nanotubes, liposomes and niosomes, etc. This self-assembly has progressively heightened interest to control the final complex structure of the nanoparticle and its associated properties. The main challenge of formulating self-assembled nanoparticle is to improve the delivery system, bioavailability, enhance circulation time, confer molecular targeting, controlled release, protection of the incorporated drug from external environment and also serve as nanocarriers for macromolecules. Ultimately, these self-assembled nanoparticles facilitate to overcome the physiological barriers in vivo. Self-assembly is an equilibrium process where both individual and assembled components are subsisting in equilibrium. It is a bottom up approach in which molecules are assembled spontaneously, non-covalently into a stable and welldefined structure. There are different approaches that have been adopted in fabrication of self-assembled nanoparticles by the researchers. The current review is enriched with strategies for nanoparticle selfassembly, associated properties, and its application in therapy.
  11. Ravichandiran V, Masilamani K, Senthilnathan B, Maheshwaran A, Wong TW, Roy P
    Curr Drug Deliv, 2017;14(8):1053-1059.
    PMID: 27572089 DOI: 10.2174/1567201813666160829100453
    BACKGROUND: Curcumin is a yellow polyphenolic chemopreventive agent isolated from the rhizomes of Curcuma longa. It is approved as Generally Regarded as Safe by US FDA. Nonetheless, its clinical success is limited due to its poor aqueous solubility, fast metabolism and short biological half-life attributes.

    OBJECTIVE: Quercetin-decorated liposomes of curcumin (QCunp) are perceived to be able to overcome these biopharmaceutical drawbacks.

    METHODS: Curcumin liposomes with/without quercetin were prepared by lipid hydration technique. The liposomes were characterized for their particle size, zeta potential, surface morphology, drug loading and release characteristics. The toxicity of the liposomes were evaluated in-vitro and their invivo efficacy were tested against Dalton's ascites lymphoma in mice.

    RESULTS: Liposomes designed showed particle size of 261.8 ± 2.1 nm with a negative zeta potential of -22.6±1.6 mV. Quercetin decorated liposomes were more effective in increasing the life span and body weight of lymphoma inflicted mice compared to those without quercetin. Similarly, the presence of quercetin also contributed to enhanced cytotoxicity of the liposomal formulation towards HT-29 cells and HCT-15 cells.

    CONCLUSION: Newer liposomal design exhibited promising potential to emerge as alternative anticancer therapeutics.

  12. Kumar P, Chaudhary B, Jain V, Baboota S, Shivanandy P, Alharbi KS, et al.
    Curr Drug Deliv, 2023;20(9):1262-1274.
    PMID: 36380413 DOI: 10.2174/1567201820666221114113637
    Molecular pharmaceutics play a critical role in the drug delivery system, representing the direct interconnection of drug bioavailability with its molecular form. There is a diversity in the molecular structures by which it affects its properties, such as amorphous form, crystalline form, partialamorphous molecular dispersion, and disordered state. The active pharmaceutical ingredient (API) and the excipients utilized in the formulation process contain various divergent modes used in the formulation process. They include better formulations of any type to obtain good quality pharmaceutical products. This review reveals how the molecular states affect the API and are important in maintaining the quality of dosage forms. Furthermore, the physio-chemical properties of the components and various pharmaceutical approaches employed in the formulation of dosage forms are studied from the point of view of molecular pharmaceutics.
  13. Zamram QAZM, Mohsin HF, Mohamad MM, Nor Hazalin NAM, Hamid KA
    Curr Drug Deliv, 2021 Apr 18.
    PMID: 33874872 DOI: 10.2174/1567201818666210419114809
    AIM: Formulating topical products for skin delivery has always been a challenge for pharmaceutical scientists to fulfil good formulation criteria. Despite the challenges, gel-based drug delivery offers some advantages such that it is non-invasive, painless, avoidance of the first-pass metabolism and has satisfactory patient compliance.

    OBJECTIVES: In this study, Chromolaena odorata gel and quercetin gel (bioactive flavonoid compound) were successfully formulated and compared with placebo and conventional wound aid gel. The chromatographic profilling was conducted to screen the presence of phytoconstituents. Subsequently, all formulated gels were subjected to physical characteristic and stability study.

    METHODS: Reverse Phase High-Performance Liquid Chromatography (RP-HPLC) of C.odorata methanolic leaves extract shows a distinct compound separation at retention time 8.4min to 34.8 min at 254nm. All gels were characterised by evaluating their rheological properties including storage modulus, loss modulus and plastic viscosity. Besides, texture analysis was performed to measure the gels' firmness, consistency, cohesiveness, and viscosity index.

    RESULTS: From the observation, C. odorata gel demonstrated better spreadability as compared to the other gels, which acquired less work and favourable to be applied onto the skin. Moreover, C. odorata gel showed no changes in organoleptic properties and proven to be stable after 30 days of accelerated stability study at 40°C ± 2°C with relative humidity (RH) of 75%± 5%.

    CONCLUSION: C. odorata gel has shown to be stable, reflecting the combination of materials used in the formulation, which did not degrade throughout the study. This work suggests the potential of this gel as a vehicle to deliver the active ingredients of C. odorata to the skin, which can be further explored as a topical application in antimicrobial wound management or other skin diseases study.

  14. Nair RS, Nair S
    Curr Drug Deliv, 2015;12(5):517-23.
    PMID: 25675336
    Mortality rate due to heart diseases increases dramatically with age. Captopril is an angiotensin converting enzyme inhibitor (ACE) used effectively for the management of hypertension. Due to short elimination half-life of captopril the oral dose is very high. Captopril is prone to oxidation and it has been reported that the oxidation rate of captopril in skin tissues is considerably low when compared to intestinal tissues. All these factors make captopril an ideal drug candidate for transdermal delivery. In this research work an effort was made to formulate transdermal films of captopril by utilizing polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) as film formers and polyethylene glycol 400 (PEG400) as a plasticizer. Dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) were used as permeation enhancers. Physicochemical parameters of the films such as appearance, thickness, weight variation and drug content were evaluated. The invitro permeation studies were carried out through excised human cadaver skin using Franz diffusion cells. The in-vitro permeation studies demonstrated that the film (P4) having the polymer ratio (PVP:PVA = 80:20) with DMSO (10%) resulted a promising drug release of 79.58% at 24 hours with a flux of 70.0 µg/cm(2)/hr. No signs of erythema or oedema were observed on the rabbit skin as a result of skin irritation study by Draize test. Based on the stability report it was confirmed that the films were physically and chemically stable, hence the prepared films are very well suited for transdermal application.
  15. 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.

  16. Shamsuddin NAM, Zulfakar MH
    Curr Drug Deliv, 2023;20(2):127-143.
    PMID: 35331113 DOI: 10.2174/1567201819666220324094234
    Natural products contain bioactive compounds that are produced naturally via synthetic or semisynthetic processes. These bioactive compounds play significant biological roles, especially for growth as well as in defense mechanisms against pathogens. Bioactive compounds in natural products have been extensively studied in recent decades for their pharmacological activities, such as anticancer, wound healing, anti-microbial, anti-inflammatory, and anti-oxidative properties. However, their pharmaceutical significance has always been hindered by their low bioavailability and instability with variations in pH, temperature, and exposure to light. Nanotechnology paves the way for the development of drug delivery systems by enhancing therapeutic efficacy. Nanostructured lipid carriers, a lipidbased drug delivery system, are recently being studied to improve the biocompatibility, biodegradability, bioavailability, solubility, permeability, and shelf life of bioactive compounds in the pharmaceutical industry. The ideal component and preparation method for bioactive compounds in nanostructured lipid carrier development is necessary for their physicochemical properties and therapeutic efficiency. Therefore, this review seeks to highlight recent developments, preparation, and application of nanostructured lipid carriers as carriers for natural bioactive compounds in improving their therapeutic potential in drug delivery systems.
  17. Tan SL, Stanslas J, Basri M, Abedi Karjiban RA, Kirby BP, Sani D, et al.
    Curr Drug Deliv, 2015;12(6):795-804.
    PMID: 26324229
    Carbamzepine (CBZ) was encapsulated in a parenteral oil-in-water nanoemulsion, in an attempt to improve its bioavailability. The particle size, polydispersity index and zeta potential were measured using dynamic light scattering. Other parameters such as pH, osmolality, viscosity, drug loading efficiency and entrapment efficiency were also recorded. Transmission electron microscopy revealed that emulsion droplets were almost spherical in shape and in the nano-range. The in vitro release profile was best characterized by Higuchi's equation. The parenteral nanoemulsion of CBZ showed significantly higher AUC0→5, AUC0→∞, AUMC0→5, AUMC0→∞, Cmax and lower clearance than that of CBZ solution in plasma. Additionally, parenteral nanoemulsion of CBZ showed significantly higher AUC0→∞, AUMC0→∞ and Cmaxthan that of CBZ solution in brain. The parenteral nanoemulsion of CBZ could therefore use as a carrier, worth exploring further for brain targeting.
  18. Hussain M
    Curr Drug Deliv, 2019;16(7):618-627.
    PMID: 30868954 DOI: 10.2174/1567201816666190313155117
    BACKGROUND: Glycyrrhizic acid (GA) is a glycoside that has shown considerable promise as a penetration enhancer and drug carrier to improve the absorption of poorly water-soluble drugs. The aggregation behavior of GA and its ability to form large micelles at higher solution concentrations are thought to contribute to these bioavailability enhancing properties. The oral absorption of Paclitaxel (PTX) for example, an anti-cancer agent which exhibits poor oral bioavailability, has been found to significantly increase in the presence of GA.

    METHODS: In an attempt to visualize the aggregation behavior of GA and its subsequent association with PTX, 100 ns molecular dynamics simulation of a 5 mM aqueous solution of GA with 10 molecules of PTX was conducted using GROMACS and an all-atom forcefield.

    RESULTS: Aggregation of GA molecules was found to occur quickly at this level of saturation leading to two stable aggregates of 13 and 17 GA molecules with an effective radius of 10.17 nm to 10.92 nm. These aggregates form not in isolation, but together with PTX molecule embedded within the structures, which reduces the number of interactions and hydrogen-bonding with water.

    CONCLUSION: GA aggregation occurs around PTX molecules in solution, forming co-joined GA-PTX cluster units at a ratio of 3:1. These clusters remain stable for the remainder of the 100ns simulation and serve to isolate and protect PTX from the aqueous environment.

  19. Eh Suk VR, Chung I, Misran M
    Curr Drug Deliv, 2020;17(4):292-302.
    PMID: 32039684 DOI: 10.2174/1567201817666200210122933
    BACKGROUND: Liposomes are mostly known to be prepared from phospholipids and lipids and have a remarkable capacity to encapsulate both lipophobic and lipophilic molecules. However, there is little research on developing fatty acid liposomes for chemotherapy.

    OBJECTIVE: We have successfully prepared mixed fatty acid liposomes from two monounsaturated fatty acids, namely oleic acid and erucic acid, which stabilised by DOPEPEG2000. The Critical Vesicular Concentration (CVC) of liposomes was found to be within 0.09 to 0.21 mmol dm-3, with an average particle size of 400 nm.

    METHODS: Encapsulation of various anticancer drugs such as folinic acid, methotrexate, doxorubicin, or irinotecan resulted in Encapsulation Efficiency (%EE) of up to 90%. Using a 3-(4, 5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) assay, the median Inhibitory Concentration (IC50) values of mixed oleic acid-erucic acid encapsulating hydrophilic drugs was remarkably reduced at the end of 24 hours of incubation with the human lung carcinoma cell line A549.

    RESULTS: The results suggest that mixed oleic acid-erucic acid liposomes are a potential new approach to further develop as an alternative vehicle of various drugs for cancer treatment.

  20. Tiash S, Othman I, Rosli R, Chowdhury EH
    Curr Drug Deliv, 2014;11(2):214-22.
    PMID: 24328684
    Most of the classical drugs used today to destroy cancer cells lead to the development of acquired resistance in those cells by limiting cellular entry of the drugs or exporting them out by efflux pumps. As a result, higher doses of drugs are usually required to kill the cancer cells affecting normal cells and causing numerous side effects. Accumulation of the therapeutic level of drugs inside the cancer cells is thus required for an adequate period of time to get drugs' complete therapeutic efficacy minimizing the side effects on normal cells. In order to improve the efficacy of chemotherapeutic drugs, nanoparticles of carbonate apatite and its strontium (Sr(2+))-substituted derivative were used in this study to make complexes with three classical anticancer drugs, methotrexate, cyclophosphamide and 5-flurouracil. The binding affinities of these drugs to apatite were evaluated by absorbance and HPLC analysis and the therapeutic efficacy of drug-apatite complexes was determined by cell viability assay. Carbonate apatite demonstrated significant binding affinity towards methotrexate and cyclophosphamide leading to more cellular toxicity than free drugs in MCF-7 and 4T1 breast cancer cells. Moreover, Sr(2+) substitution in carbonate apatite with resulting tiny particles less than 100 nm in diameter further promoted binding of methotrexate to the nanocarriers indicating that Sr(2+)-substituted apatite nanoparticles have the high potential for loading substantial amount of anti-cancer drugs with eventual more therapeutic effectiveness.
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