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  1. Mahmood S, Kiong KC, Tham CS, Chien TC, Hilles AR, Venugopal JR
    AAPS PharmSciTech, 2020 Oct 14;21(7):285.
    PMID: 33057878 DOI: 10.1208/s12249-020-01810-0
    Currently, pharmaceutical research is directed wide range for developing new drugs for oral administration to target disease. Acyclovir formulation is having common issues of short half-life and poor permeability, causing messy treatment which results in patient incompliance. The present study formulates a lipid polymeric hybrid nanoparticles for antiviral acyclovir (ACV) agent with Phospholipon® 90G (lecithin), chitosan, and polyethylene glycol (PEG) to improve controlled release of the drugs. The study focused on the encapsulation of the ACV in lipid polymeric particle and their sustained delivery. The formulation developed for the self-assembly of chitosan and lecithin to form a shell encapsulating acyclovir, followed by PEGylation. Optimisation was performed via Box-Behnken Design (BBD), forming nanoparticles with size of 187.7 ± 3.75 nm, 83.81 ± 1.93% drug-entrapped efficiency (EE), and + 37.7 ± 1.16 mV zeta potential. Scanning electron microscopy and transmission electron microscopy images displayed spherical nanoparticles formation. Encapsulation of ACV and complexity with other physical parameters are confirmed through analysis using Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. Nanoparticle produced was capable of achieving 24-h sustained release in vitro on gastric and intestinal environments. Ex vivo study proved the improvement of acyclovir's apparent permeability from 2 × 10-6 to 6.46 × 10-6 cm s-1. Acyclovir new formulation was achieved to be stable up to 60 days for controlled release of the drugs. Graphical abstract.
  2. Gnaneshwar PV, Sudakaran SV, Abisegapriyan S, Sherine J, Ramakrishna S, Rahim MHA, et al.
    Mater Sci Eng C Mater Biol Appl, 2019 Mar;96:337-346.
    PMID: 30606541 DOI: 10.1016/j.msec.2018.11.033
    Far-flung evolution in tissue engineering enabled the development of bioactive and biodegradable materials to generate biocomposite nanofibrous scaffolds for bone repair and replacement therapies. Polymeric bioactive nanofibers are to biomimic the native extracellular matrix (ECM), delivering tremendous regenerative potentials for drug delivery and tissue engineering applications. It's been known from few decades that Zinc oxide (ZnO) nanoparticles are enhancing bone growth and providing proliferation of osteoblasts when incorporated with hydroxyapatite (HAp). We attempted to investigate the interaction between the human foetal osteoblasts (hFOB) with ZnO doped HAp incorporated biocomposite poly(L-lactic acid)-co-poly(ε-caprolactone) and silk fibroin (PLACL/SF) nanofibrous scaffolds for osteoblasts mineralization in bone tissue regeneration. The present study, we doped ZnO with HAp (ZnO(HAp) using the sol-gel ethanol condensation technique. The properties of PLACL/SF/ZnO(HAp) biocomposite nanofibrous scaffolds enhanced with doped and blended ZnO/HAp were characterized using Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Contact angle and Tensile studies to determine the morphology, functionality, wettability and stability. The in vitro study results showed that the addition of ZnO and HAp enhances the secretion of bone mineral matrix (98%) with smaller fiber diameter (139.4 ± 27 nm) due to the presence of silk fibroin showing potential tensile properties (322.4%), and increased the proliferation of osteoblasts for bone tissue regeneration.
  3. Ezhilarasu H, Ramalingam R, Dhand C, Lakshminarayanan R, Sadiq A, Gandhimathi C, et al.
    Int J Mol Sci, 2019 Oct 18;20(20).
    PMID: 31635374 DOI: 10.3390/ijms20205174
    Aloe vera (AV) and tetracycline hydrochloride (TCH) exhibit significant properties such as anti-inflammatory, antioxidant and anti-bacterial activities to facilitate skin tissue engineering. The present study aims to develop poly-ε-caprolactone (PCL)/ AV containing curcumin (CUR), and TCH loaded hybrid nanofibrous scaffolds to validate the synergistic effect on the fibroblast proliferation and antimicrobial activity against Gram-positive and Gram-negative bacteria for wound healing. PCL/AV, PCL/CUR, PCL/AV/CUR and PCL/AV/TCH hybrid nanofibrous mats were fabricated using an electrospinning technique and were characterized for surface morphology, the successful incorporation of active compounds, hydrophilicity and the mechanical property of nanofibers. SEM revealed that there was a decrease in the fiber diameter (ranging from 360 to 770 nm) upon the addition of AV, CUR and TCH in PCL nanofibers, which were randomly oriented with bead free morphology. FTIR spectra of various electrospun samples confirmed the successful incorporation of AV, CUR and TCH into the PCL nanofibers. The fabricated nanofibrous scaffolds possessed mechanical properties within the range of human skin. The biocompatibility of electrospun nanofibrous scaffolds were evaluated on primary human dermal fibroblasts (hDF) by MTS assay, CMFDA, Sirius red and F-actin stainings. The results showed that the fabricated PCL/AV/CUR and PCL/AV/TCH nanofibrous scaffolds were non-toxic and had the potential for wound healing applications. The disc diffusion assay confirmed that the electrospun nanofibrous scaffolds possessed antibacterial activity and provided an effective wound dressing for skin tissue engineering.
  4. Suteris NN, Yasin A, Misnon II, Roslan R, Zulkifli FH, Rahim MHA, et al.
    Int J Biol Macromol, 2021 Dec 29;198:147-156.
    PMID: 34971642 DOI: 10.1016/j.ijbiomac.2021.12.006
    This article demonstrates the development of nanofibrous cloths by electrospinning of renewable materials, i.e., curcumin-loaded 90% cellulose acetate (CA)/10% poly(ε-caprolactone) (PCL), for applications in regenerative medicine. The CA is derived from the biomass waste of the oil palm plantation (empty fruit bunch). The nanofiber scaffolds are characterized for the fiber morphology, microstructure, thermal properties, and wettability. The optimized smooth and bead-free electrospun fiber cloth contains 90% CA and 10% PCL in two curcumin compositions (0.5 and 1 wt%). The role of curcumin is shown to be two-fold: the first is its function as a drug and the second is its role in lowering the water contact angle and increasing the hydrophilicity. The hydrophilicity enhancements are related to the hydrogen bonding between the components. The enhanced hydrophilicity contributed to improve the swelling behavior of the scaffolds; the CA/PCL/Cur (0.5%) and the CA/PCL/Cur (1.0%) showed swelling of ~700 and 950%, respectively, in phosphate-buffered saline (PBS). The drug-release studies revealed the highest cumulative drug release of 60% and 78% for CA/PCL/Cur (0.5%) and CA/PCL/Cur (1.0%) nanofibers, respectively. The in-vitro studies showed that CA/PCL/Cur (0.5 wt%) and CA/PCL/Cur (1.0 wt%) nanofiber scaffolds facilitate a higher proliferation and expression of actin in fibroblasts than those scaffolds without curcumin for wound healing applications.
  5. Dhand C, Balakrishnan Y, Ong ST, Dwivedi N, Venugopal JR, Harini S, et al.
    Int J Nanomedicine, 2018;13:4473-4492.
    PMID: 30122921 DOI: 10.2147/IJN.S159770
    Introduction: In search for cross-linkers with multifunctional characteristics, the present work investigated the utility of quaternary ammonium organosilane (QOS) as a potential cross-linker for electrospun collagen nanofibers. We hypothesized that the quaternary ammonium ions improve the electrospinnability by reducing the surface tension and confer antimicrobial properties, while the formation of siloxane after alkaline hydrolysis could cross-link collagen and stimulate cell proliferation.

    Materials and methods: QOS collagen nanofibers were electrospun by incorporating various concentrations of QOS (0.1%-10% w/w) and were cross-linked in situ after exposure to ammonium carbonate. The QOS cross-linked scaffolds were characterized and their biological properties were evaluated in terms of their biocompatibility, cellular adhesion and metabolic activity for primary human dermal fibroblasts and human fetal osteoblasts.

    Results and discussion: The study revealed that 1) QOS cross-linking increased the flexibility of otherwise rigid collagen nanofibers and improved the thermal stability; 2) QOS cross-linked mats displayed potent antibacterial activity and 3) the biocompatibility of the composite mats depended on the amount of QOS present in dope solution - at low QOS concentrations (0.1% w/w), the mats promoted mammalian cell proliferation and growth, whereas at higher QOS concentrations, cytotoxic effect was observed.

    Conclusion: This study demonstrates that QOS cross-linked mats possess anti-infective properties and confer niches for cellular growth and proliferation, thus offering a useful approach, which is important for hard and soft tissue engineering and regenerative medicine.

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