Displaying publications 81 - 100 of 147 in total

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  1. A prospective study evaluating wound healing with sea cucumber gel compared with hydrogel in treatment of skin graft donor sites
    Poh Yuen Wen A, Halim AS, Mat Saad AZ, Mohd Nor F, Wan Sulaiman WA
    Complement Ther Med, 2018 Dec;41:261-266.
    PMID: 30477850 DOI: 10.1016/j.ctim.2018.10.006
    BACKGROUND: Gamat (sea-cucumber) is a natural occurring fauna which is popularly used as traditional medication in Southeast Asian countries. There have been many animal studies done on its' biochemical properties and its' effects in vivo. The effect of gamat on human cutaneous wounds was studied using a split-skin graft donor site wound.

    METHODS: This was a comparative case-control study done on patients in Hospital Universiti Sains Malaysia (Hospital USM), requiring split-thickness skin grafting, whereby, the skin graft donor site was divided to almost equal halves, and applied with both gamat-based gel on one side, with Duoderm® hydrogel on the other side. The epithelialization of the wounds was observed and compared on days 10, 14 and 21. Pain score, and pruritus score were also observed. Repeated measure analysis of variance (ANOVA) test and Paired t-test was used to test statistical significance accordingly.

    RESULTS: No significant differences were seen in rates of epithelialization of wounds on days 10, 14 and 21 (p > 0.01). No significant difference was also seen in the pain score and pruritus score (p > 0.01).

    CONCLUSIONS: A gamat-based gel is comparable to conventional hydrogels in treatment of split-skin graft donor site. No adverse effects were observed in either group.

    Matched MeSH terms: Hydrogels/pharmacology*
  2. Fulltext Moringa oleifera leaf extract loaded hydrogel for diabetic wound healing
    Natarajan, Satheesh Babu, Das, SreemoyKanti, Chandran, Suriyakala Perumal, Aung, Myo Oo, Kanneppady, Sowmya Shar, Entezarian, Maryam, et al.
    Malaysian Journal of Medical Research, 2018;2(2):35-41.
    MyJurnal
    Diabetic wounds (DW) are a chronic, non-healing wound on the feet of diabetic patients that pose a serious challenge to world health. Around 84% of diabetic patients undergo lower leg amputations. Though numerous topical and systemic drugs have been used to heal the DW, these drugs have led to the emergence and subsequent rapid overgrowth of resistant bacterial strains, side effects and toxicity. Many herbal plants have very important role in wound healing because they promote the natural repair mechanisms. Moringa oleifera (MO) is an important medicinal plant which has an impressive range of medicinal uses including antimicrobial, anti-inflammatory, antidiabetic, antioxidant and anticancer activities.Recently few researchers reported that MO extracts have effective wound healing property due to the presence of rich flavonoids and vicenin-2. The objective of the present study was to develop hydrogel formulations loaded with Moringa oleifera leaves extract. The prepared hydrogels were evaluated for physical appearance, rheological behavior, skin irritation and wound-healing power in streptozotocin-induced diabetic male wistar albino rats. Results showed that all hydrogel formulations exhibited good and acceptable physical properties. All the animals tolerated the applied gels and no signs of irritations were noticed during the skin irritation study. The in-vivo wound healing studies showed a time dependent increase in percentage of wound, a contraction which is higher than that produced by the control groups. These contractions were statistically significant (P
    Matched MeSH terms: Hydrogels
  3. Phomopsidione nanoparticles coated contact lenses reduce microbial keratitis causing pathogens
    Bin Sahadan MY, Tong WY, Tan WN, Leong CR, Bin Misri MN, Chan M, et al.
    Exp Eye Res, 2019 01;178:10-14.
    PMID: 30243569 DOI: 10.1016/j.exer.2018.09.011
    Microbial keratitis is the infection caused by pathogenic microorganisms that commonly occurs among the contact lens users. Various antimicrobial compounds were coated on contact lenses to kill keratitis causing microorganisms, however these compounds caused several adverse side effects. Hence, the aim of this study is to develop a silicone hydrogel contact lens coated with phomopsidione nanoparticle that inhibit keratitis causing clinical isolates. Phomopsidione nanoparticles were synthesized using polyvinyl alcohol as encapsulant. The nanoparticles showed an average size of 77.45 nm, with neutral surface charge. Two drug release patterns were observed in the drug release profile, which are the initial slow release phase with extended drug release (release rate 46.65 μg/h), and the burst release phase observed on Day 2 (release rate 2224.49 μg/h). This well-regulated drug delivery system enables the control of drug release to meet the therapeutic requirements. On agar diffusion assay, 3 out of 5 test microorganisms were inhibited by phomopsidione nanoparticle coated contact lenses, including two Gram negative bacteria. Besides, all test microorganisms showed at least 99% of growth reduction, with the treatment of the contact lens model. The drug loaded onto the nanoparticles is sufficient to prevent the bacterial growth. In conclusion, this study provides an effective alternative to combat keratitis-causing microorganisms among contact wearers.
    Matched MeSH terms: Hydrogels
  4. Structural and bone marrow stem cell biocompatibility studies of hydrogel synthesized via chemo-enzymatic route
    Latfi ASA, Pramanik S, Poon CT, Gumel AM, Lai KW, Annuar MSM, et al.
    J Biomater Appl, 2019 01;33(6):854-865.
    PMID: 30458659 DOI: 10.1177/0885328218812490
    Natural biopolymers have many attractive medical applications; however, complications due to fibrosis caused a reduction in diffusion and dispersal of nutrients and waste products. Consequently, severe immunocompatibility problems and poor mechanical and degradation properties in synthetic polymers ensue. Hence, the present study investigates a novel hydrogel material synthesized from caprolactone, ethylene glycol, ethylenediamine, polyethylene glycol, ammonium persulfate, and tetramethylethylenediamine via chemo-enzymatic route. Spectroscopic analyses indicated the formation of polyurea and polyhydroxyurethane as the primary building block of the hydrogel starting material. Biocompatibility studies showed positive observation in biosafety test using direct contact cytotoxicity assay in addition to active cellular growth on the hydrogel scaffold based on fluorescence observation. The synthesized hydrogel also exhibited (self)fluorescence properties under specific wavelength excitation. Hence, synthesized hydrogel could be a potential candidate for medical imaging as well as tissue engineering applications as a tissue expander, coating material, biosensor, and drug delivery system.
    Matched MeSH terms: Hydrogels/chemical synthesis; Hydrogels/chemistry*
  5. Safety and efficacy of dermal fibroblast conditioned medium (DFCM) fortified collagen hydrogel as acellular 3D skin patch
    Maarof M, Mh Busra MF, Lokanathan Y, Bt Hj Idrus R, Rajab NF, Chowdhury SR
    Drug Deliv Transl Res, 2019 02;9(1):144-161.
    PMID: 30547385 DOI: 10.1007/s13346-018-00612-z
    Skin substitutes are one of the main treatments for skin loss, and a skin substitute that is readily available would be the best treatment option. However, most cell-based skin substitutes require long production times, and therefore, patients endure long waiting times. The proteins secreted from the cells and tissues play vital roles in promoting wound healing. Thus, we aimed to develop an acellular three-dimensional (3D) skin patch with dermal fibroblast conditioned medium (DFCM) and collagen hydrogel for immediate treatment of skin loss. Fibroblasts from human skin samples were cultured using serum-free keratinocyte-specific media (KM1 or KM2) and serum-free fibroblast-specific medium (FM) to obtain DFCM-KM1, DFCM-KM2, and DFCM-FM, respectively. The acellular 3D skin patch was soft, semi-solid, and translucent. Collagen mixed with DFCM-KM1 and DFCM-KM2 showed higher protein release compared to collagen plus DFCM-FM. In vitro and in vivo testing revealed that DFCM and collagen hydrogel did not induce an immune response. The implantation of the 3D skin patch with or without DFCM on the dorsum of BALB/c mice demonstrated a significantly faster healing rate compared to the no-treatment group 7 days after implantation, and all groups had complete re-epithelialization at day 17. Histological analysis confirmed the structure and integrity of the regenerated skin, with positive expression of cytokeratin 14 and type I collagen in the epidermal and dermal layer, respectively. These findings highlight the possibility of using fibroblast secretory factors together with collagen hydrogel in an acellular 3D skin patch that can be used allogeneically for immediate treatment of full-thickness skin loss.
    Matched MeSH terms: Hydrogels/chemistry
  6. Mucoadhesive guargum hydrogel inter-connected chitosan-g-polycaprolactone micelles for rifampicin delivery
    Yuan X, Amarnath Praphakar R, Munusamy MA, Alarfaj AA, Suresh Kumar S, Rajan M
    Carbohydr Polym, 2019 Feb 15;206:1-10.
    PMID: 30553301 DOI: 10.1016/j.carbpol.2018.10.098
    Natural polymer guar gum has one of the highest viscosities in water solution and hence, these are significantly used in pharmaceutical applications. Guar gum inter-connected micelles as a new carrier has been developed for poor water soluble rifampicin drug. The hydrogel inter-connected micelle core was formulated as a hydrophilic inner and hydrophobic outer core by using guar gum/chitosan/polycaprolactone and the carrier interaction with rifampicin was confirmed by FT-IR. The morphological observations were carried out through TEM, SEM and AFM analysis. The encapsulation efficiency and in-vitro drug release behavior of prepared hydrogel based micelle system was analyzed by UV-vis spectrometry. The anti-bacterial activity against K. pneumoniae and S. aureus was studied by observing their ruptured surface by SEM. The cytotoxicity study reveals that the pure polymeric system has no toxic effect whereas drug loaded ones showed superior activity against THP-1 cells. From the cell apoptosis analyses, the apoptosis was carried out in a time dependent manner. The cell uptake behavior was also observed in THP-1 cells which indicate that the hydrogel based micelle system is an excellent material for the mucoadhesive on intracellular alveolar macrophage treatment.
    Matched MeSH terms: Hydrogels/chemical synthesis; Hydrogels/toxicity; Hydrogels/chemistry*
  7. Natural and synthetic polymer-based smart biomaterials for management of ulcerative colitis: a review of recent developments and future prospects
    Sohail M, Mudassir, Minhas MU, Khan S, Hussain Z, de Matas M, et al.
    Drug Deliv Transl Res, 2019 04;9(2):595-614.
    PMID: 29611113 DOI: 10.1007/s13346-018-0512-x
    Ulcerative colitis (UC) is an inflammatory disease of the colon that severely affects the quality of life of patients and usually responds well to anti-inflammatory agents for symptomatic relief; however, many patients need colectomy, a surgical procedure to remove whole or part of the colon. Though various types of pharmacological agents have been employed for the management of UC, the lack of effectiveness is usually predisposed to various reasons including lack of target-specific delivery of drugs and insufficient drug accumulation at the target site. To overcome these glitches, many researchers have designed and characterized various types of versatile polymeric biomaterials to achieve target-specific delivery of drugs via oral route to optimize their targeting efficiency to the colon, to improve drug accumulation at the target site, as well as to ameliorate off-target effects of chemotherapy. Therefore, the aim of this review was to summarize and critically discuss the pharmaceutical significance and therapeutic feasibility of a wide range of natural and synthetic biomaterials for efficient drug targeting to colon and rationalized treatment of UC. Among various types of biomaterials, natural and synthetic polymer-based hydrogels have shown promising targeting potential due to their innate pH responsiveness, sustained and controlled release characteristics, and microbial degradation in the colon to release the encapsulated drug moieties. These characteristic features make natural and synthetic polymer-based hydrogels superior to conventional pharmacological strategies for the management of UC.
    Matched MeSH terms: Hydrogels/administration & dosage
  8. In vivo evaluation of bacterial cellulose/acrylic acid wound dressing hydrogel containing keratinocytes and fibroblasts for burn wounds
    Mohamad N, Loh EYX, Fauzi MB, Ng MH, Mohd Amin MCI
    Drug Deliv Transl Res, 2019 04;9(2):444-452.
    PMID: 29302918 DOI: 10.1007/s13346-017-0475-3
    The healing of wounds, including those from burns, currently exerts a burden on healthcare systems worldwide. Hydrogels are widely used as wound dressings and in the field of tissue engineering. The popularity of bacterial cellulose-based hydrogels has increased owing to their biocompatibility. Previous study demonstrated that bacterial cellulose/acrylic acid (BC/AA) hydrogel increased the healing rate of burn wound. This in vivo study using athymic mice has extended the use of BC/AA hydrogel by the addition of human epidermal keratinocytes and human dermal fibroblasts. The results showed that hydrogel loaded with cells produces the greatest acceleration on burn wound healing, followed by treatment with hydrogel alone, compared with the untreated group. The percentage wound reduction on day 13 in the mice treated with hydrogel loaded with cells (77.34 ± 6.21%) was significantly higher than that in the control-treated mice (64.79 ± 6.84%). Histological analysis, the expression of collagen type I via immunohistochemistry, and transmission electron microscopy indicated a greater deposition of collagen in the mice treated with hydrogel loaded with cells than in the mice administered other treatments. Therefore, the BC/AA hydrogel has promising application as a wound dressing and a cell carrier.
    Matched MeSH terms: Hydrogels/administration & dosage*
  9. Controlled release studies through chitosan-based hydrogel synthesized at different polymerization stages
    Md Rasib SZ, Md Akil H, Khan A, Abdul Hamid ZA
    Int J Biol Macromol, 2019 May 01;128:531-536.
    PMID: 30708001 DOI: 10.1016/j.ijbiomac.2019.01.190
    An earlier study showed that the behaviour of chitosan-poly(methacrylic acid‑co‑N‑isopropylacrylamide) [chitosan‑p(MAA‑co‑NIPAM)] hydrogels synthesized at different reaction times are affected with regard to their pH and temperature sensitivities. The study was continued in this paper to identify the effects of different reaction times on the degradation, efficiency of rifampicin (Rif) loading and the Rif release profile under two different pH conditions (acidic and basic). The results that were obtained showed that the hydrogel had a faster degradation rate in the acidic condition than in the basic condition, where there was a loss of approximately 50% and 20%, respectively in its original weight within two weeks. The Rif loading efficiency was within 50% and the drug release was controlled by characteristics that were developed beyond the polymerization stages of the synthesis. Therefore, the reaction time for the synthesis of the hydrogel can be considered as a way to control the behaviour of the hydrogel as well as to modify the drug release profile in the chitosan‑p(MAA‑co‑NIPAM) hydrogel.
    Matched MeSH terms: Hydrogels/chemical synthesis*; Hydrogels/chemistry*
  10. Sodium carboxymethyl cellulose hydrogels containing reduced graphene oxide (rGO) as a functional antibiofilm wound dressing
    Ali NH, Amin MCIM, Ng SF
    J Biomater Sci Polym Ed, 2019 06;30(8):629-645.
    PMID: 30896336 DOI: 10.1080/09205063.2019.1595892
    Biofilms comprise bacteria attached to wound surfaces and are major contributors to non-healing wounds. It was found that the increased resistance of biofilms to antibiotics allows wound infections to persist chronically in spite of antibiotic therapy. In this study, the reduced form of graphene oxide (rGO) was explored as plausible antibiofilm agents. The rGO was synthesized via reducing the functional groups of GO. Then, rGO were characterized using zetasizer, X-ray photoelectron spectroscopy, UV-Vis spectroscopy and FESEM. The rGO were then formulated into sodium carboxymethyl cellulose (NaCMC) hydrogels to form rGO hydrogel and tested for antibiofilm activities in vitro using XTT test, and in vivo biofilm formation assay using nematodes C. elegans. Reduced GO hydrogel was successfully formed by reducing the functional groups of GO, and a reduction of up to 95% of functional groups was confirmed with X-ray photoelectron spectroscopy analysis. XTT tests confirmed that rGO hydrogels reduced biofilm formation by S. aureus (81-84%) and P. aeruginosa (50-62%). Fluorescence intensity also confirmed that rGO hydrogel can inhibit biofilm bacteria in C. elegans experiments. This study implied that rGO hydrogel is an effective antibiofilm agent for infected wounds.
    Matched MeSH terms: Hydrogels/pharmacology; Hydrogels/chemistry*
  11. Novel chitosan derivative based composite scaffolds with enhanced angiogenesis; potential candidates for healing chronic non-healing wounds
    Rizwan M, Yahya R, Hassan A, Yar M, Abd Halim AA, Rageh Al-Maleki A, et al.
    J Mater Sci Mater Med, 2019 Jun 11;30(6):72.
    PMID: 31187295 DOI: 10.1007/s10856-019-6273-3
    The success of wound healing depends upon the proper growth of vascular system in time in the damaged tissues. Poor blood supply to wounded tissues or tissue engineered grafts leads to the failure of wound healing or rejection of grafts. In present paper, we report the synthesis of novel organosoluble and pro-angiogenic chitosan derivative (CSD) by the reaction of chitosan with 1,3-dimethylbarbituric acid and triethylorthoformate (TEOF). The synthesized material was characterized by FTIR and 13C-NMR to confirm the incorporated functional groups and new covalent connectivities. Biodegradability of the synthesized chitosan derivative was tested in the presence of lysozyme and was found to be comparable with CS. The cytotoxicity and apoptosis effect of new derivative was determined against gastric adenocarcinoma (AGS) cells and was found to be non-toxic. The CSD was found to be soluble in majority of organic solvents. It was blended with polycaprolactone (PCL) to form composite scaffolds. From an ex ovo CAM assay, it was noted that CSD stimulated the angiogenesis.
    Matched MeSH terms: Hydrogels/chemistry
  12. Superabsorbent hydrogel from oil palm empty fruit bunch cellulose and sodium carboxymethylcellulose
    Salleh KM, Zakaria S, Sajab MS, Gan S, Kaco H
    Int J Biol Macromol, 2019 Jun 15;131:50-59.
    PMID: 30844455 DOI: 10.1016/j.ijbiomac.2019.03.028
    A green regenerated superabsorbent hydrogel was fabricated with mixtures of dissolved oil palm empty fruit bunch (EFB) cellulose and sodium carboxymethylcellulose (NaCMC) in NaOH/urea system. The formation of hydrogel was aided with epichlorohydrin (ECH) as a crosslinker. The resultant regenerated hydrogel was able to swell >80,000% depending on the NaCMC concentrations. The hydrogel absorbed water rapidly upon exposure to water up to 48 h and gradually declined after 72 h. The crosslinked of covalent bond of COC between dissolved EFB cellulose (EFBC) with NaCMC was confirmed with Attenuated total reflectance Fourier transform infrared (ATR-FT-IR) spectroscopy. Crystallinity and thermal stability of the hydrogel samples were depended on the concentrations of NaCMC, crosslinking, and swelling process. The strength and stability of crosslinked network was studied by examining the gel fraction of hydrogel. This study explored the swelling ability and probable influenced factors towards physical and chemical properties of hydrogel.
    Matched MeSH terms: Hydrogels/chemical synthesis; Hydrogels/chemistry*
  13. The remarkable three-dimensional network structure of bacterial cellulose for tissue engineering applications
    Halib N, Ahmad I, Grassi M, Grassi G
    Int J Pharm, 2019 Jul 20;566:631-640.
    PMID: 31195074 DOI: 10.1016/j.ijpharm.2019.06.017
    Cellulose is a natural homopolymer, composed of β-1,4- anhydro-d-glucopyranose units. Unlike plant cellulose, bacterial cellulose (BC), obtained from species belonging to the genera of Acetobacter, Rhizobium, Agrobacterium, and Sarcina through various cultivation methods and techniques, is produced in its pure form. BC is produced in the form of gel-like, never dry sheet with tremendous mechanical properties. Containing up to 99% of water, BC hydrogel is considered biocompatible thus finding robust applications in the health industry. Moreover, BC three-dimensional structure closely resembles the extracellular matrix (ECM) of living tissue. In this review, we focus on the porous BC morphology particularly suited to host oxygen and nutrients thus providing conducive environment for cell growth and proliferation. The remarkable BC porous morphology makes this biological material a promising templet for the generation of 3D tissue culture and possibly for tissue-engineered scaffolds.
    Matched MeSH terms: Hydrogels*
  14. Fabrication and evaluation of bacterial nanocellulose/poly(acrylic acid)/graphene oxide composite hydrogel: Characterizations and biocompatibility studies for wound dressing
    Chen XY, Low HR, Loi XY, Merel L, Mohd Cairul Iqbal MA
    J Biomed Mater Res B Appl Biomater, 2019 08;107(6):2140-2151.
    PMID: 30758129 DOI: 10.1002/jbm.b.34309
    Graphene oxide (GO) is a potential material for wound dressing due to its excellent biocompatibility and mechanical properties. This study evaluated the effects of GO concentration on the synthesis of bacterial nanocellulose (BNC)-grafted poly(acrylic acid) (AA)-graphene oxide (BNC/P(AA)/GO) composite hydrogel and its potential as wound dressing. Hydrogels were successfully synthesized via electron-beam irradiation. The hydrogels were characterized by their mechanical properties, bioadhesiveness, water vapor transmission rates (WVTRs), water retention abilities, water absorptivity, and biocompatibility. Fourier transform infrared analysis showed the successful incorporation of GO into hydrogel. Thickness, gel fraction determination and morphological study revealed that increased GO concentration in hydrogels leads to reduced crosslink density and larger pore size, resulting in increased WVTR. Thus, highest swelling ratio was found in hydrogel with higher amount of GO (0.09 wt %). The mechanical properties of the composite hydrogel were maintained, while its hardness and bioadhesion were reduced with higher GO concentration in the hydrogel, affirming the durable and easy removable properties of a wound dressing. Human dermal fibroblast cell attachment and proliferation studies showed that biocompatibility of hydrogel was improved with the inclusion of GO in the hydrogel. Therefore, BNC/P(AA)/GO composite hydrogel has a potential application as perdurable wound dressing. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2140-2151, 2019.
    Matched MeSH terms: Hydrogels/chemistry*
  15. Xeno-free and feeder-free culture and differentiation of human embryonic stem cells on recombinant vitronectin-grafted hydrogels
    Chen LH, Sung TC, Lee HH, Higuchi A, Su HC, Lin KJ, et al.
    Biomater Sci, 2019 Aug 14.
    PMID: 31411209 DOI: 10.1039/c9bm00418a
    Recombinant vitronectin-grafted hydrogels were developed by adjusting surface charge of the hydrogels with grafting of poly-l-lysine for optimal culture of human embryonic stem cells (hESCs) under xeno- and feeder-free culture conditions, with elasticity regulated by crosslinking time (10-30 kPa), in contrast to conventional recombinant vitronectin coating dishes, which have a fixed stiff surface (3 GPa). hESCs proliferated on the hydrogels for over 10 passages and differentiated into the cells derived from three germ layers indicating the maintenance of pluripotency. hESCs on the hydrogels differentiated into cardiomyocytes under xeno-free culture conditions with much higher efficiency (80% of cTnT+ cells) than those on conventional recombinant vitronectin or Matrigel-coating dishes just only after 12 days of induction. It is important to have an optimal design of cell culture biomaterials where biological cues (recombinant vitronectin) and physical cues (optimal elasticity) are combined for high differentiation of hESCs into specific cell lineages, such as cardiomyocytes, under xeno-free and feeder-free culture conditions.
    Matched MeSH terms: Hydrogels
  16. Fulltext Pharmacological properties of Centella asiatica hydrogel in accelerating wound healing in rabbits
    Sh Ahmed A, Taher M, Mandal UK, Jaffri JM, Susanti D, Mahmood S, et al.
    BMC Complement Altern Med, 2019 Aug 14;19(1):213.
    PMID: 31412845 DOI: 10.1186/s12906-019-2625-2
    BACKGROUND: Various extracts of Centella asiatica (Apiaceae) and its active constituent, asiaticoside, have been reported to possess wound healing property when assessed using various in vivo and in vitro models. In an attempt to develop a formulation with accelerated wound healing effect, the present study was performed to examine in vivo efficacy of asiaticoside-rich hydrogel formulation in rabbits.

    METHODS: Asiaticoside-rich fraction was prepared from C. asiatica aerial part and then incorporated into polyvinyl alcohol/polyethylene glycol (PVA/PEG) hydrogel. The hydrogel was subjected to wound healing investigation using the in vivo incision model.

    RESULTS: The results obtained demonstrated that: i) the hydrogel formulation did not cause any signs of irritation on the rabbits' skin and; ii) enhanced wound healing 15% faster than the commercial cream and > 40% faster than the untreated wounds. The skin healing process was seen in all wounds marked by formation of a thick epithelial layer, keratin, and moderate formation of granulation tissues, fibroblasts and collagen with no fibrinoid necrosis detected.

    CONCLUSION: The asiaticoside-rich hydrogel developed using the freeze-thaw method was effective in accelerating wound healing in rabbits.

    Matched MeSH terms: Hydrogels/administration & dosage; Hydrogels/chemistry
  17. Molecular Evaluation of Oral Immunogenicity of Hepatitis B Antigen Delivered by Hydrogel Microparticles
    Chen XY, Butt AM, Mohd Amin MCI
    Mol Pharm, 2019 09 03;16(9):3853-3872.
    PMID: 31398038 DOI: 10.1021/acs.molpharmaceut.9b00483
    The development of oral vaccine formulation is crucial to facilitate an effective mass immunization program for various vaccine-preventable diseases. In this work, the efficacy of hepatitis B antigen delivered by bacterial nanocellulose/poly(acrylic acid) composite hydrogel microparticles (MPs) as oral vaccine carriers was assessed to induce both local and systemic immunity. Optimal pH-responsive swelling, mucoadhesiveness, protein drug loading, and drug permeability were characterized by MPs formulated with minimal irradiation doses and acrylic acid concentration. The composite hydrogel materials of bacterial nanocellulose and poly(acrylic acid) showed significantly greater antigen release in simulated intestinal fluid while ensuring the integrity of antigen. In in vivo study, mice orally vaccinated with antigen-loaded hydrogel MPs showed enhanced vaccine immunogenicity with significantly higher secretion of mucosal immunoglobulin A, compared to intramuscular vaccinated control. The splenocytes from the same group demonstrated lymphoproliferation and significant increased secretion of interleukin-2 cytokines upon stimulation with hepatitis B antigen. Expression of CD69 in CD4+ T lymphocytes and CD19+ B lymphocytes in splenocytes from mice orally vaccinated with antigen-loaded hydrogel MPs was comparable to that of the intramuscular vaccinated control, indicating early activation of lymphocytes elicited by our oral vaccine formulation in just two doses. These results demonstrated the potential of antigen-loaded hydrogel MPs as an oral vaccination method for hepatitis B.
    Matched MeSH terms: Hydrogels/administration & dosage*; Hydrogels/chemistry
  18. Enhanced paracellular delivery of vaccine by hydrogel microparticles-mediated reversible tight junction opening for effective oral immunization
    Chen XY, Butt AM, Mohd Amin MCI
    J Control Release, 2019 10;311-312:50-64.
    PMID: 31465827 DOI: 10.1016/j.jconrel.2019.08.031
    The current conventional injectable vaccines face several drawbacks such as inconvenience and ineffectiveness in mucosal immunization. Therefore, the current development of effective oral vaccines is vital to enable the generation of dual systemic and mucosal immunity. In the present study, we examine the potential of pH-responsive bacterial nanocellulose/polyacrylic acid (BNC/PAA) hydrogel microparticles (MPs) as an oral vaccine carrier. In-vitro entrapment efficiency and release study of Ovalbumin (Ova) demonstrated that as high as 72% of Ova were entrapped in the hydrogel, and the release of loaded Ova was pH-dependent. The released Ova remained structurally conserved as evident by Western blot and circular dichroism. Hydrogel MPs reduced the TEER measurement of HT29MTX/Caco2/Raji B triple co-culture monolayer by reversibly opening the tight junctions (TJs) as shown in the TEM images. The ligated ileal loop assay revealed that hydrogel MPs could facilitate the penetration of FITC-Ova into the Peyer's patches in small intestine. Ova and cholera toxin B (CTB) were utilized in in-vivo oral immunization as model antigen and mucosal adjuvant. The in-vivo immunization revealed mice orally administered with Ova and CTB-loaded hydrogel MPs generated significantly higher level of serum anti-Ova IgG and mucosal anti-Ova IgA in the intestinal washes, compared to intramuscular administrated Ova. These results conclude that BNC/PAA hydrogel MPs is a potential oral vaccine carrier for effective oral immunization.
    Matched MeSH terms: Hydrogels/administration & dosage*
  19. A dual-action chitosan-based nanogel system of triclosan and flurbiprofen for localised treatment of periodontitis
    Aminu N, Chan SY, Yam MF, Toh SM
    Int J Pharm, 2019 Oct 30;570:118659.
    PMID: 31493495 DOI: 10.1016/j.ijpharm.2019.118659
    This study aimed to develop a dual action, namely anti-inflammatory and antimicrobial, nanogels (NG) for the treatment of periodontitis using triclosan (TCS) and flurbiprofen (FLB). Triclosan, an antimicrobial drug, was prepared as nanoparticles (NPs) using poly-ε-caprolactone (PCL), while flurbiprofen, an anti-inflammatory drug, was directly loaded in a chitosan (CS) based hydrogel. The entwinement of both NPs and hydrogel loaded systems resulted in the NG. The characterisation data confirmed that the developed formulation consists of nanosized spherical structures and displays pH-dependent swelling/erosion and temperature-responsiveness. Besides, the NG exhibited adequate bioadhesiveness using the chicken pouch model and displayed antibacterial activity through the agar plate method. An in-vivo study of the NG on experimental periodontitis (EP) rats confirmed the dual antibacterial and anti-inflammatory effects which revealed an excellent therapeutic outcome. In conclusion, a dual action NG was successfully developed and proved to have superior therapeutic effects in comparison to physical mixtures of the individual drugs.
    Matched MeSH terms: Hydrogels/chemistry
  20. Fulltext Hydrogel Fluorescence Microsensor with Fluorescence Recovery for Prolonged Stable Temperature Measurements
    Hashim H, Maruyama H, Akita Y, Arai F
    Sensors (Basel), 2019 Nov 29;19(23).
    PMID: 31795304 DOI: 10.3390/s19235247
    This work describes a hydrogel fluorescence microsensor for prolonged stable temperature measurements. Temperature measurement using microsensors has the potential to provide information about cells, tissues, and the culture environment, with optical measurement using a fluorescent dye being a promising microsensing approach. However, it is challenging to achieve stable measurements over prolonged periods with conventional measurement methods based on the fluorescence intensity of fluorescent dye because the excited fluorescent dye molecules are bleached by the exposure to light. The decrease in fluorescence intensity induced by photobleaching causes measurement errors. In this work, a photobleaching compensation method based on the diffusion of fluorescent dye inside a hydrogel microsensor is proposed. The factors that influence compensation in the hydrogel microsensor system are the interval time between measurements, material, concentration of photo initiator, and the composition of the fluorescence microsensor. These factors were evaluated by comparing a polystyrene fluorescence microsensor and a hydrogel fluorescence microsensor, both with diameters of 20 µm. The hydrogel fluorescence microsensor made from 9% poly (ethylene glycol) diacrylate (PEGDA) 575 and 2% photo initiator showed excellent fluorescence intensity stability after exposure (standard deviation of difference from initial fluorescence after 100 measurement repetitions: within 1%). The effect of microsensor size on the stability of the fluorescence intensity was also evaluated. The hydrogel fluorescence microsensors, with sizes greater than the measurement area determined by the axial resolution of the confocal microscope, showed a small decrease in fluorescence intensity, within 3%, after 900 measurement repetitions. The temperature of deionized water in a microchamber was measured for 5400 s using both a thermopile and the hydrogel fluorescence microsensor. The results showed that the maximum error and standard deviation of error between these two sensors were 0.5 °C and 0.3 °C, respectively, confirming the effectiveness of the proposed method.
    Matched MeSH terms: Hydrogels
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