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  1. Bor G, Mat Azmi ID, Yaghmur A
    Ther Deliv, 2019 02;10(2):113-132.
    PMID: 30678550 DOI: 10.4155/tde-2018-0062
    The emergence of nanomedicine as an innovative and promising alternative technology shows many advantages over conventional cancer therapies and provides new opportunities for early detection, improved treatment, and diagnosis of cancer. Despite the cancer nanomedicines' capability of delivering chemotherapeutic agents while providing lower systemic toxicity, it is paramount to consider the cancer complexity and dynamics for bridging the translational bench-to-bedside gap. It is important to conduct appropriate investigations for exploiting the tumor microenvironment, and achieving a more comprehensive understanding of the fundamental biological processes in cancer and their roles in modulating nanoparticle-protein interactions, blood circulation, and tumor penetration. This review provides an overview of the current cancer nanomedicines, the major challenges, and the future opportunities in this research area.
  2. Loo YS, Bose RJ, McCarthy JR, Mat Azmi ID, Madheswaran T
    Drug Discov Today, 2021 04;26(4):902-915.
    PMID: 33383213 DOI: 10.1016/j.drudis.2020.12.017
    Smart nanocarriers obtained from bacteria and viruses offer excellent biomimetic properties which has led to significant research into the creation of advanced biomimetic materials. Their versatile biomimicry has application as biosensors, biomedical scaffolds, immobilization, diagnostics, and targeted or personalized treatments. The inherent natural traits of biomimetic and bioinspired bacteria- and virus-derived nanovesicles show potential for their use in clinical vaccines and novel therapeutic drug delivery systems. The past few decades have seen significant progress in the bioengineering of bacteria and viruses to manipulate and enhance their therapeutic benefits. From a pharmaceutical perspective, biomimetics enable the safe integration of naturally occurring bacteria and virus particles to achieve high, stable rates of cellular transfection/infection and prolonged circulation times. In addition, biomimetic technologies can overcome safety concerns associated with live-attenuated and inactivated whole bacteria or viruses. In this review, we provide an update on the utilization of bacterial and viral particles as drug delivery systems, theranostic carriers, and vaccine/immunomodulation modalities.
  3. Loo YS, Zahid NI, Madheswaran T, Ikeno S, Nurdin A, Mat Azmi ID
    Mol Pharm, 2023 Sep 04;20(9):4611-4628.
    PMID: 37587099 DOI: 10.1021/acs.molpharmaceut.3c00333
    Lyotropic liquid crystalline nanoassemblies (LLCNs) are internally self-assembled (ISA)-somes formed by amphiphilic molecules in a mixture comprising a lipid, stabilizer, and/or surfactant and aqueous media/dispersant. LLCNs are unique nanoassemblies with versatile applications in a wide range of biomedical functions. However, they comprise a nanosystem that is yet to be fully explored for targeted systemic treatment of breast cancer. In this study, LLCNs proposed for gemcitabine and thymoquinone (Gem-TQ) co-delivery were prepared from soy phosphatidylcholine (SPC), phytantriol (PHYT), or glycerol monostearate (MYVR) in optimized ratios containing a component of citric and fatty acid ester-based emulsifier (Grinsted citrem) or a triblock copolymer, Pluronic F127 (F127). Hydrodynamic particle sizes determined were below 400 nm (ranged between 96 and 365 nm), and the series of nanoformulations displayed negative surface charge. Nonlamellar phases identified by small-angle X-ray scattering (SAXS) profiles comprise the hexagonal, cubic, and micellar phases. In addition, high entrapment efficiency that accounted for 98.3 ± 0.1% of Gem and 99.5 ± 0.1% of TQ encapsulated was demonstrated by the coloaded nanocarrier system, SPC/citrem/Gem-TQ hexosomes. Low cytotoxicity of SPC-citrem hexosomes was demonstrated in MCF10A cells consistent with hemo- and biocompatibility observed in zebrafish (Danio rerio) embryos for up to 96 h postfertilization (hpf). SPC/citrem/Gem-TQ hexosomes demonstrated IC50 of 24.7 ± 4.2 μM in MCF7 breast cancer cells following a 24 h treatment period with the moderately synergistic interaction between Gem and TQ retained (CI = 0.84). Taken together, biocompatible SPC/citrem/Gem-TQ hexosomes can be further developed as a multifunctional therapeutic nanodelivery approach, plausible for targeting breast cancer cells by incorporation of targeting ligands.
  4. Maslizan M, Haris MS, Ajat M, Md Jamil SNA, Azhar SC, Zahid NI, et al.
    Chem Phys Lipids, 2024 May;260:105377.
    PMID: 38325712 DOI: 10.1016/j.chemphyslip.2024.105377
    Atorvastatin calcium (ATV) and proanthocyanidins (PAC) have a strong antioxidant activity, that can benefit to reduce the atherosclerotic plaque progression. Unfortunately, the bioavailability of ATV is greatly reduced due to its limited drug solubility while the PAC drug is unstable upon exposure to the atmospheric oxygen. Herein, the lyotropic liquid crystalline nanoparticles (LLCNPs) constructed by a binary mixture of soy phosphatidylcholine (SPC) and citric acid ester of monoglyceride (citrem) at different weight ratios were used to encapsulate the hydrophobic ATV and hydrophilic PAC. The LLCNPs were further characterized by small-angle X-ray scattering and dynamic light scattering. Depending on the lipid composition, the systems have a size range of 140-190 nm and were able to encapsulate both drugs in the range of 90-100%. Upon increasing the citrem content of drug-loaded LLCNPs, the hexosomes (H2) was completely transformed to an emulsified inverse micellar (L2). The optimum encapsulation efficiency (EE) of ATV and PAC were obtained in citrem/SPC weight ratio 4:1 (L2) and 1:1 (H2), respectively. There was a substantial change in the mean size and PDI of the nanoparticles upon 30 days of storage with the ATV-loaded LLCNPs exhibiting greater colloidal instability than PAC-loaded LLCNPs. The biphasic released pattern (burst released at the initial stage followed by the sustained released at the later stage) was perceived in ATV formulation, while the burst drug released pattern was observed in PAC formulations that could be attributed by its internal H2 structure. Interestingly, the cytokine studies showed that the PAC-LLCNPs promisingly up regulate the expressions of tumor necrosis factor-alpha (TNF-α) better than the drug-free and ATV-loaded LLCNPs samples. The structural tunability of citrem/SPC nanoparticles and their effect on physicochemical characteristic, biological activities and potential as an alternative drug delivery platform in the treatment of atherosclerosis are discussed.
  5. Amerhaider Nuar NN, Md Jamil SNA, Li F, Mat Azmi ID, Chiang PC, Choong TSY
    Polymers (Basel), 2022 Sep 15;14(18).
    PMID: 36146006 DOI: 10.3390/polym14183866
    Nanoscale calcium peroxide (nCP) has turned out to be one of the effective and environmentally friendly approaches for wastewater remediation purposes. The rapid hydrolysis of nCPs and burst oxygen release caused by the high surface-to-volume ratio of nCPs could surpass the appropriate demand for oxygenation and pollutant degradation in the aqueous system. Thus, coated oxidants (COs) have been prepared using polymeric materials to ensure long-term efficacy and slow-release capability. Therefore, the nCPs were first prepared using dextran as a stabilizer to prevent irreversible agglomeration by the chemical precipitation method and had an average mean size of 2.33 ± 0.81 nm. The synthesized nCPs were then coated with dextran to produce dextran-coated nCPs. Their characteristics and effectiveness in doxycycline (DOX) degradation were assessed. The characterization of nCPs and dextran-coated nCPs was performed using X-ray diffractometry (XRD), field emission scanning electron microscopy (FESEM), fourier transform infrared spectroscopy (FTIR), Brunauer, Emmett and Teller analysis (BET), dynamic light scattering (DLS) and thermogravimetric analysis (TGA) techniques. This work suggests that dextran-coated nCPs are beneficial in wastewater treatment practice in terms of the long-term efficacy of DOX degradation potential.
  6. Amerhaider Nuar NN, Md Jamil SNA, Choong TSY, Mat Azmi ID, Abdul Romli NA, Abdullah LC, et al.
    Polymers (Basel), 2023 Mar 06;15(5).
    PMID: 36904568 DOI: 10.3390/polym15051327
    One of the most significant environmental problems in the world is the massive release of dye wastewater from the dyeing industry. Therefore, the treatment of dyes effluents has received significant attention from researchers in recent years. Calcium peroxide (CP) from the group of alkaline earth metal peroxides acts as an oxidizing agent for the degradation of organic dyes in water. It is known that the commercially available CP has a relatively large particle size, which makes the reaction rate for pollution degradation relatively slow. Therefore, in this study, starch, a non-toxic, biodegradable and biocompatible biopolymer, was used as a stabilizer for synthesizing calcium peroxide nanoparticles (Starch@CPnps). The Starch@CPnps were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Brunauer-Emmet-Teller (BET), dynamic light scattering (DLS), thermogravimetric analysis (TGA), energy dispersive X-ray analysis (EDX) and scanning electron microscopy (SEM). The degradation of organic dyes, methylene blue (MB), using Starch@CPnps as a novel oxidant was studied using three different parameters: initial pH of the MB solution, calcium peroxide initial dosage and contact time. The degradation of the MB dye was carried out via a Fenton reaction, and the degradation efficiency of Starch@CPnps was successfully achieved up to 99%. This study shows that the potential application of starch as a stabilizer can reduce the size of the nanoparticles as it prevents the agglomeration of the nanoparticles during synthesis.
  7. Leu JSL, Teoh JJX, Ling ALQ, Chong J, Loo YS, Mat Azmi ID, et al.
    Pharmaceutics, 2023 May 06;15(5).
    PMID: 37242663 DOI: 10.3390/pharmaceutics15051421
    Due to their distinctive structural features, lyotropic nonlamellar liquid crystalline nanoparticles (LCNPs), such as cubosomes and hexosomes, are considered effective drug delivery systems. Cubosomes have a lipid bilayer that makes a membrane lattice with two water channels that are intertwined. Hexosomes are inverse hexagonal phases made of an infinite number of hexagonal lattices that are tightly connected with water channels. These nanostructures are often stabilized by surfactants. The structure's membrane has a much larger surface area than that of other lipid nanoparticles, which makes it possible to load therapeutic molecules. In addition, the composition of mesophases can be modified by pore diameters, thus influencing drug release. Much research has been conducted in recent years to improve their preparation and characterization, as well as to control drug release and improve the efficacy of loaded bioactive chemicals. This article reviews current advances in LCNP technology that permit their application, as well as design ideas for revolutionary biomedical applications. Furthermore, we have provided a summary of the application of LCNPs based on the administration routes, including the pharmacokinetic modulation property.
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