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1.
ADMET DMPK ; 11(4): 615-627, 2023.
Article in English | MEDLINE | ID: mdl-37937245

ABSTRACT

Introduction: Olanzapine (OLZ) is a psychotropic class drug commonly used to treat schizophrenia, bipolar disorder, and acute manic episodes. It has less water solubility, resulting in a slow dissolution rate and oral bioavailability. Therefore, the development in oral dosage forms is required to enhance the drug solubility. Method: The solid dispersion of olanzapine is prepared by spray drying technique. The solution of polyvinylpyrrolidone K-30 (PVP K-30), mono amino glycyrrhizinate pentahydrate (GLY), OLZ and silicon dioxide were dissolved in distilled water and ethanol and spray dried to get the solid dispersion. Solid dispersion was characterized for surface morphology, solubility, encapsulation efficiency (EE), X-ray diffraction (X-RD), Differential Scanning Calorimeter (DSC) and drug-polymer interaction by Fourier transforms infrared spectroscopy. Results: The amorphous nature of the drug's incorporation in solid dispersion was confirmed by X-RD analysis. Prepared solid dispersion showed higher solubility, 11.51 mg, than pure OLZ (0.983 mg ml-1), while the range of EE was found to be between 64 to 90 %. Conclusions: The solubility and dissolution rate of the OLZ can effectively increase by spray-dried solid dispersion. Plackett-Burman screening design plays a vital role in understanding the effect of independent variables on EE and solubility.

2.
Article in English | MEDLINE | ID: mdl-37656353

ABSTRACT

The presence of trace metals in wastewater brings serious environmental pollution that threatens human health as well as the ecosystem throughout the world due to their non-biodegradability nature. The present study focuses on the bioremediation of toxic trace metals, namely arsenic (As), cadmium (Cd), and chromium (Cr), using Acalypha wilkesiana leaf raw biomass. The optimization of various process variables was done to determine the removal percentage of trace metal using Acalypha wilkesiana leaf raw biomass, and the optimum conditions were an adsorbent dose of 0.5 g, contact time 10 h, 8 h, and 10 h, process temperature 30 °C, initial concentration of trace metal as 30 µg/L, 30 mg//L, and 40 mg/L, and pH of 7.5, 7 and 7.5 for As5+, and Cd2+ and Cr6+, respectively. Acalypha wilkesiana leaf raw biomass is characterized using a scanning electron microscope (SEM), energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and Fourier transformation infrared spectroscopy (FTIR), zeta potential before and after adsorption of the trace metal ions. The study was well fitted for the equilibrium data for Langmuir isotherm for As5+, Cd2+, and Cr6+, Freundlich for As5+, Dubinin-Radushkevinch (D-R) for Cr6+, and Temkin for As5+ and Cr6+. The adsorption of all three trace metals was confirmed by the kinetics and thermodynamic studies to be following pseudo-second-order kinetics with endothermic as well as spontaneous processes, respectively. Thus, the present study indicates Acalypha wilkesiana leaf raw biomass as an effective and efficient novel biosorbent to remediate different trace metals from aqueous systems with its possible application in existing and novel methods for wastewater management.

3.
Chemosphere ; 338: 139504, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37453520

ABSTRACT

The non-scientific disposal of antibiotics has resulted in massive contamination of the bioactive molecules in the aquatic ecosystem. The presence of antibiotics in the effluents limits the biodegradation of micropollutants by affecting the micro-ecological balance. Hence this study aims to remove doxycycline antibiotics from wastewater using biochar. Elemental analysis of the biochar revealed C, Si and N as most abundant content while BET analysis confirmed the mesoporous nature of the adsorbent. The XRD and Raman spectra confirmed amorphic sp2 carbon dominant structure in the biochar. The adsorption mechanism was predicted, correlating the charge distribution and FTIR analysis. The effects of different process parameters were studied using CCD, ANOVA, and RSM. Moreover, the different kinetic models revealed that the pseudo-second-order kinetics model was the best fit and film layer diffusion was the dominant contributor. The isotherm study indicated the high adsorption capacity of the biochar and its non-ionic nature. Thermodynamics study established the spontaneity and exothermic nature. The results suggested no significant change in antibiotic removal efficiency across different system (pond water (97.13%), river water (98.11%), seawater (96.84%), tap water (99.13%), and distilled water (99.74%)). For the desorption of the antibiotic from the biochar surface, 90% ethanol was the most efficient (98.9%), and upon recrystallization by solvent evaporation, 98.7% of the antibiotic of the initial load was recovered. Hence, the implementation of this described process would enable resource recovery along with water treatment, which is not possible with existing approaches. The cost analysis of the whole process revealed that biochar preparation was the bulk expense and the process would be self-sustainable even if the price of the recovered antibiotic would be set at less than half ($41/kg) of the current market price ($94/kg) of the API. Thus, the process endorses a successful circular economy approach toward societal and economic sustainability.


Subject(s)
Anti-Bacterial Agents , Doxycycline , Waste Disposal, Fluid , Water Pollutants, Chemical , Adsorption , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry , Charcoal/chemistry , Doxycycline/analysis , Doxycycline/chemistry , Ecosystem , Kinetics , Oryza/chemistry , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/chemistry , Waste Disposal, Fluid/methods
4.
Ocul Immunol Inflamm ; 31(8): 1594-1602, 2023 Oct.
Article in English | MEDLINE | ID: mdl-34637663

ABSTRACT

AIM: To study the long-term efficacy and safety of Ozurdex as anti-inflammatory monotherapy in the management of tuberculosis-associated intermediate uveitis (TBIU). METHODS: Retrospective analysis of eyes with TBIU that received Ozurdex as anti-inflammatory monotherapy with a follow-up of at least 1 year. RESULTS: 13 eyes (2 pseudophakic) of 11 patients were included. Mean BCVA improved from 0.65 to 0.11 at 3 months (p = .0005) and remained 0.11 at 1 year. Mean central foveal thickness improved from 452.87µ to 187.25µ at 3 months (p = .0009) and 184.62µ at 1 year in 8 eyes with CME. Mean vitreous haze improved from 2.38 to 0.11 at 3 months with no recurrences at 1 year. Mean IOP increased from 13.15mmHg to 15.53mmHg (p = .013) at 2 months and reduced to 12.46mmHg by 1 year. None required antiglaucoma medication. One eye underwent cataract surgery. The mean follow-up was 18.4 months. CONCLUSION: Ozurdex is safe and efficacious in TBIU as anti-inflammatory monotherapy in conjunction with antitubercular therapy.


Subject(s)
Macular Edema , Tuberculosis , Uveitis, Intermediate , Uveitis , Humans , Glucocorticoids/therapeutic use , Retrospective Studies , Macular Edema/drug therapy , Drug Implants , Anti-Inflammatory Agents/therapeutic use , Dexamethasone , Intravitreal Injections , Uveitis, Intermediate/complications , Uveitis, Intermediate/diagnosis , Uveitis, Intermediate/drug therapy , Uveitis/complications , Uveitis/diagnosis , Uveitis/drug therapy
5.
Appl Biochem Biotechnol ; 195(8): 4832-4850, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36576655

ABSTRACT

Worldwide ever-augmenting urbanization, modernization, and industrialization have contributed to the release of pernicious compounds and a variety of pollutants into the environment. The pollutants discharged due to industrialization are of global concern. Industrial waste and effluent are comprised of hazardous organic and inorganic chemicals including heavy metals which pose a significant threat to the environment and may bring about numerous diseases or abnormalities in human beings. This brings on greater urgency for remediation of these polluted soil and water using sustainable approaches and mechanisms. In the present research, a multi-metal-resistant, gram-positive, non-virulent bacterial strain Bacillus sp. GH-s29 was isolated from contaminated groundwater of Bhojpur district, Bihar, India. The strain had the potential to develop a biofilm that was able to remediate different heavy metals [arsenic, cadmium, and chromium] from individual and multi-heavy metal solutions. Maximum removal for As (V), Cd (II), and Cr (VI) from individual-metal and the multi-metal solution was observed to be 73.65%, 57.37%, 61.62%, and 48.92%, 28.7%, and 35.46%, respectively. SEM-EDX analysis revealed the sequestration of multi-heavy metals by bacterial biofilm. Further characterization by FTIR analysis ensured that the presence of negatively charged functional groups on the biofilm-EPS such as hydroxyl, phosphate, sulfate, and carboxyl helps in binding to the positively charged metal ions. Thus, Bacillus sp. GH-s29 proved to be an effective and economical alternative for different heavy metal remediation from contaminated sites.


Subject(s)
Bacillus , Environmental Pollutants , Metals, Heavy , Soil Pollutants , Humans , Bacillus/metabolism , Soil Pollutants/metabolism , Bacteria/metabolism , Cadmium/pharmacology , Environmental Pollutants/metabolism , Biofilms , Water/pharmacology , Biodegradation, Environmental
6.
Environ Monit Assess ; 194(12): 898, 2022 Oct 17.
Article in English | MEDLINE | ID: mdl-36251091

ABSTRACT

The vast usage of synthetic plastics has led to the global problem of plastic pollution which in turn has positively impacted the concerns regarding microplastic pollution. The major factor responsible for the increased level of pollution is the smaller size of microplastics which helps in its transportation across the globe. It has been found in most remote areas like glaciers and Antarctic regions where it is difficult for other contaminants to reach. This is ensured by the physicochemical cycle of plastic. They can either be produced for different applications or generated through the fragmentation of large plastic particles. Different studies have shown the accumulation of microplastics in different organisms, especially in aquatic animals leading to their entry into the food chain. The ultimate fate of the microplastics is accumulation inside the human body posing the risk of different health conditions like cancer, diabetes, and allergic reactions. The present review summarizes a detailed discussion on the current status of microplastic pollution, their effect on different organisms, and its impact on human health with a case study on the human health risk assessment for analyzing the global rate of microplastic ingestion.


Subject(s)
Microplastics , Water Pollutants, Chemical , Animals , Ecosystem , Environmental Monitoring , Humans , Plastics/chemistry , Risk Assessment , Water Pollutants, Chemical/analysis
7.
Chemosphere ; 307(Pt 4): 136115, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35995185

ABSTRACT

Biosorption is an environment-friendly and economic technique to remediate heavy metals from aqueous systems. In the present study, Artocarpus heterophyllus seed powder was used as a biosorbent material to remove different heavy metals. The batch adsorption studies confirmed the higher removal percentage of the Artocarpus heterophyllus (jackfruit) seed powder for arsenic (As5+), cadmium (Cd2+), and chromium (Cr6+) while lower efficiency was observed for other heavy metals like copper (Cu2+), zinc (Zn2+) and nickel (Ni2+). Optimization of different process parameters was carried out and the optimum conditions were: adsorbent weight of 0.5 g for the initial concentration of heavy metals as 40 µg/L, 30 mg/L, and 30 mg/L; contact time of 10 h, 8 h, and 6 h; process temperature from 25 to 30 °C; pH of 7, 7.5, and 7.5 for As5+, Cd2+, and Cr6+ respectively. The SEM-EDX, FTIR, and XRD studies before and after adsorption of heavy metals resulted in affirmative observations. The equilibrium data of the study was well fitted for Langmuir isotherm for As5+, Cd2+, and Cr6+, Freundlich for As5+and Cr6+, Dubinin-Radushkevich for Cd2+and Cr6+. The kinetic and thermodynamic study confirmed that the adsorption of all three heavy metals was following the pseudo-second-order kinetics with the endothermic and spontaneous process respectively. The cost analysis of the process confirmed that the whole process was cost-effective compared to other processes. Hence the Artocarpus heterophyllus seed powder was verified for its high heavy metal remediation efficiency from aqueous environments along with the added advantages of being eco-friendly and economic compared to other alternatives.


Subject(s)
Arsenic , Artocarpus , Metals, Heavy , Water Pollutants, Chemical , Adsorption , Arsenic/analysis , Biodegradation, Environmental , Cadmium/analysis , Chromium/analysis , Copper/analysis , Hydrogen-Ion Concentration , Kinetics , Metals, Heavy/analysis , Nickel/analysis , Powders , Seeds/chemistry , Thermodynamics , Water/analysis , Water Pollutants, Chemical/analysis , Zinc/analysis
8.
Drug Deliv Transl Res ; 12(12): 3063-3082, 2022 12.
Article in English | MEDLINE | ID: mdl-35525868

ABSTRACT

The research study reflects the development of novel voriconazole (VCZ) loaded nanoparticles (NPs) for prolonged delivery for the management of ocular diseases. The in situ ophthalmic gel was prepared by incorporating NPs into carboxymethyl chitosan (CMCh) and poloxamer. The central composite design was used to optimize the process for the preparation of nanoparticles by the o/w solvent evaporation method. The developed nanoparticles were evaluated for the encapsulation efficiency (89.6 ± 1.2%), particle size (219.3 ± 1.8 nm), polydispersity index (PDI, 0.1), zeta potential (- 21.1 ± 1.12 mV), saturation solubility, DSC study, and drug release. The etherification process grafts carboxyl surface functional groups, on chitosan, and was confirmed by FTIR and NMR studies. The developed CMCh-poloxamer based gelling system was found to be clear and transparent with gelation temperature varying from 33 to 40 °C. The nanoparticle-loaded gel containing CMCh demonstrated enhanced antifungal activity against Candida albicans. The optimized batch containing CMCh showed improved mucoadhesion by 2.86-fold compared to VCZ nanosuspension. The drug release was prolonged up to 8 h with an ex vivo study suggesting the enhanced permeation across goat cornea estimated via fluorescent microscope. The hen's egg chorioallantoic membrane study revealed that the formulation was non-irritant and tolerated by the chorioallantoic membrane. The present study concludes that the VCZ loaded nanoparticulate in situ ophthalmic gel using CMCh may act as a potential alternative for traditional eye drops.


Subject(s)
Chitosan , Nanoparticles , Animals , Female , Poloxamer/chemistry , Chitosan/chemistry , Voriconazole , Chickens , Nanoparticles/chemistry , Gels/chemistry , Particle Size , Colloids , Drug Carriers/chemistry
10.
Biomacromolecules ; 21(10): 4030-4042, 2020 10 12.
Article in English | MEDLINE | ID: mdl-32902971

ABSTRACT

Thread size and polymer composition are critical properties to consider for achieving a positive healing outcome with a wound dressing. Three-dimensional (3D) printed scaffolds and electrospun mats both offer distinct advantages as replaceable wound dressings. This research aims to determine if the thread size and polymer compositions of the scaffolds affect skin wound healing outcomes, an aspect that has not been adequately explored. Using a modular polymer platform, four polyester direct-write 3D printed scaffolds and electrospun mats were fabricated into wound dressings. The dressings were applied to splinted, full thickness skin wounds in an excisional wound rat model and evaluated against control wounds to which no dressing was applied. Wound closure rates and reduction of the wound bed width were not affected by the thread size or polymer composition. However, epidermal thickness was larger in wounds treated with electrospun dressings and was slightly affected by the polymer composition. Two of the four tested polymer compositions lead to delayed reorganization of granulation tissues. Moreover, enhanced angiogenesis was seen in wounds treated with 3D printed dressings compared to those treated with electrospun dressings. The results from this study can be used to inform the choice of dressing architecture and polymer compositions to achieve positive wound healing outcomes.


Subject(s)
Bandages , Polymers , Animals , Polyesters , Printing, Three-Dimensional , Rats , Wound Healing
11.
Adv Biosyst ; 4(8): e1900250, 2020 08.
Article in English | MEDLINE | ID: mdl-32686345

ABSTRACT

Poor oxygen transport is a major obstacle currently for 3D microtissue culture platforms, which at this time cannot be grown large enough to be truly physiologically relevant and replicate adult human organ functions. To overcome internal oxygen transport deficiencies, oxygenating microgels are formed utilizing perfluorocarbon (PFC) modified chitosan and a highly scalable water-in-oil miniemulsion method. Microgels that are on the order of a cell diameter (≈10 µm) are formed allowing them to directly associate with cells when included in 3D spheroid culture, while not being internalized. The presence of immobilized PFCs in these microgels allows for enhancement and tuning of oxygen transport when incorporated into cultured microtissues. As such, it is demonstrated that incorporating oxygenating microgels at ratios ranging from 50:1 to 400:1 (# of cells:# of microgels) into dense human fibroblast-based spheroids facilitated the growth of larger human cell-based spheroids, especially at the highest incorporation percentages (50:1), which lacked defined hypoxic cores. Quantification of total double-stranded (ds)-DNA, a measure of number of live cells, demonstrated similar results to hypoxia quantification, showing more ds-DNA due incorporation of oxygenating microgels. Finally, oxygen concentrations are measured at different depths within spheroids directly and confirmed higher oxygen partial pressures due to chitosan-PFC microspheres.


Subject(s)
Chitosan/metabolism , Fibroblasts/drug effects , Microgels/chemistry , Oxygen/metabolism , Spheroids, Cellular/drug effects , Biological Transport , Cell Hypoxia , DNA/metabolism , Emulsions , Fibroblasts/cytology , Fibroblasts/metabolism , Fluorocarbons/chemistry , Foreskin/cytology , Foreskin/metabolism , Halogenation , Humans , Infant, Newborn , Male , Primary Cell Culture , Spheroids, Cellular/cytology , Spheroids, Cellular/metabolism
12.
Ultrason Sonochem ; 67: 105128, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32298975

ABSTRACT

Recovery of lactose from the whey using sonocrystallization was studied experimentally. The effect of sonication medium and irradiation power levels was evaluated using three different ultrasonic equipments. Effects of various parameters such as sonication time, pH of the medium, antisolvent (acetone and acetone-ethanol mixture) and concentration of lactose were determined. The optimal parametric conditions were analyzed using differential scanning calorimetry, thermogravimetric analysis, particle size distribution, and zeta potential measurements. Overall, the highest lactose recovery was obtained using a mixture of acetone and ethanol as antisolvent in bath sonication as well as atomization process.

13.
Adv Wound Care (New Rochelle) ; 8(8): 374-385, 2019 Aug 01.
Article in English | MEDLINE | ID: mdl-31346492

ABSTRACT

Objective: Oxygen therapy has shown promising results for treating diabetic wounds. However, clinically used oxygen therapies are cumbersome and expensive. Thus, there is a need to develop a localized oxygenating treatment that is easy to use and inexpensive. Approach: In this study, we tested a previously developed hydrogel sheet wound dressing based on fluorinated methacrylamide chitosan (MACF) for enhanced oxygenation and compared it with a commercial sheet hydrogel dressing, AquaDerm™, and no treatment controls in a splinted transgenic diabetic mouse wound model. Results: AquaDerm exhibited poor wound closure response compared with the MACF oxygenating hydrogel sheet dressing (MACF+O2) and no treatment. Histological analysis revealed enhanced collagen synthesis and neovascularization upon MACF+O2 treatment as indicated by higher collagen content and number of blood vessels/capillaries compared with AquaDerm and no treatment. MACF+O2 also improved wound collagen fiber alignment, thus demonstrating improved skin tissue maturation. Nuclear magnetic resonance spectroscopy-based biodistribution analysis revealed that the degradation products of the MACF-based dressing did not accumulate in lung, liver, and kidney tissues of the treated animals after 14 days of treatment. Innovation: This study presents the first application of a unique oxygenating biomaterial (MACF) made into a moist hydrogel wound dressing for treating diabetic wounds. Conclusion: The results of this study confirm the benefits of this novel biomaterial approach for improving regenerated tissue structure in diabetic wound healing.

14.
Cells Tissues Organs ; 205(5-6): 350-371, 2018.
Article in English | MEDLINE | ID: mdl-30273927

ABSTRACT

Oxygen is a vital source of energy necessary to sustain and complete embryonic development. Not only is oxygen the driving force for many cellular functions and metabolism, but it is also involved in regulating stem cell fate, morphogenesis, and organogenesis. Low oxygen levels are the naturally preferred microenvironment for most processes during early development and mainly drive proliferation. Later on, more oxygen and also nutrients are needed for organogenesis and morphogenesis. Therefore, it is critical to maintain oxygen levels within a narrow range as required during development. Modulating oxygen tensions is performed via oxygen homeostasis mainly through the function of hypoxia-inducible factors. Through the function of these factors, oxygen levels are sensed and regulated in different tissues, starting from their embryonic state to adult development. To be able to mimic this process in a tissue engineering setting, it is important to understand the role and levels of oxygen in each developmental stage, from embryonic stem cell differentiation to organogenesis and morphogenesis. Taking lessons from native tissue microenvironments, researchers have explored approaches to control oxygen tensions such as hemoglobin-based, perfluorocarbon-based, and oxygen-generating biomaterials, within synthetic tissue engineering scaffolds and organoids, with the aim of overcoming insufficient or nonuniform oxygen levels and nutrient supply.


Subject(s)
Embryonic Development , Oxygen/metabolism , Tissue Engineering , Animals , Cell Differentiation , Cell Hypoxia , Embryonic Stem Cells/cytology , Embryonic Stem Cells/metabolism , Humans , Morphogenesis , Organogenesis , Oxygen/analysis , Tissue Engineering/methods
15.
PLoS One ; 13(9): e0203371, 2018.
Article in English | MEDLINE | ID: mdl-30183754

ABSTRACT

Wound healing involves multiple interrelated processes required to lead to successful healing outcomes. Phagocytosis, inflammation, cell proliferation, angiogenesis, energy production, and collagen synthesis are all directly or indirectly dependent on oxygen. Along with other critical factors, such as nutrition and comorbidities, availability of oxygen is a key determinant of healing success. Previously, we have presented a novel oxygenated hydrogel material that can be made into dressings for continuous localized oxygen delivery to wounds. In this study, an acute porcine wound model was used to test the healing benefits of these oxygenated MACF (MACF + O2) hydrogel dressings compared to controls, which included commercial Derma-GelTM hydrogel dressings. Wound closure and histological analyses were performed to assess re-epithelialization, collagen synthesis, angiogenesis, and keratinocyte maturation. Results from these assays revealed that wounds treated with MACF + O2 hydrogel dressings closed faster as compared to Derma-Gel (p<0.05). Targeted metabolomics via liquid chromatography separation and mass spectrometric detection (LC-MS/MS) and a biochemical assay determined the concentration of hydroxyproline in wound samples at days 14 and 21, showing that MACF + O2 hydrogel dressings improved wound healing via an upregulated collagen synthesis pathway as compared to Derma-Gel (p<0.05). Histological evidence showed that MACF + O2 hydrogel dressings improve new blood vessel formation and keratinocyte maturation over all other treatments.


Subject(s)
Acrylamides , Bandages , Chitosan , Fluorocarbon Polymers , Hydrogels , Wound Healing/drug effects , Wounds and Injuries/therapy , Acrylamides/chemistry , Acrylamides/pharmacology , Acute Disease , Animals , Chitosan/chemistry , Chitosan/pharmacology , Disease Models, Animal , Fluorocarbon Polymers/chemistry , Fluorocarbon Polymers/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Swine , Wounds and Injuries/pathology
16.
J Biomed Mater Res A ; 105(8): 2368-2374, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28371332

ABSTRACT

Antioxidants play an important role in regulating overabundant reactive oxygen species (ROS) in wound healing to reduce oxidative stress and inflammation. In this work, we demonstrate for the first time that functionalization of methacrylamide chitosan (MAC) with aliphatic pentadecafluoro chains, to synthesize pentadecafluoro-octanoyl methacrylamide chitosan (MACF), enhances the antioxidant capacity of the MAC base hydrogel material, while being able to deliver oxygen for future enhanced wound healing applications. As such, MACF was shown to sequester more nitric oxide (p < 0.01) and hydroxyl (p < 0.0001) radicals as compared to the negative control even when delivering additional oxygen. MACF's beneficial antioxidant capacity was further confirmed in in vitro cell culture experiments using human dermal fibroblasts stressed with 2,2'-azobis(2-methylpropionamidine) dihydrochloride (AAPH). © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2368-2374, 2017.


Subject(s)
Acrylamides/pharmacology , Antioxidants/pharmacology , Chitosan/pharmacology , Fluorocarbons/pharmacology , Oxygen/administration & dosage , Reactive Oxygen Species/metabolism , Acrylamides/chemistry , Antioxidants/chemistry , Cells, Cultured , Chitosan/analogs & derivatives , Fibroblasts/drug effects , Fibroblasts/metabolism , Fluorocarbons/chemistry , Halogenation , Humans , Hydrogel, Polyethylene Glycol Dimethacrylate/chemistry , Hydrogel, Polyethylene Glycol Dimethacrylate/pharmacology , Oxidative Stress/drug effects , Wound Healing
17.
Acta Biomater ; 36: 164-74, 2016 05.
Article in English | MEDLINE | ID: mdl-27000552

ABSTRACT

UNLABELLED: In this study, methacrylamide chitosan modified with perfluorocarbon chains (MACF) is used as the base material to construct hydrogel dressings for treating dermal wounds. MACF hydrogels saturated with oxygen (+O2) are examined for their ability to deliver and sustain oxygen, degrade in a biological environment, and promote wound healing in an animal model. The emerging technique of metabolomics is used to understand how MACF+O2 hydrogel dressings improve wound healing. Results indicate that MACF treatment facilitates oxygen transport rate that is two orders of magnitude greater than base MAC hydrogels. MACF hydrogel dressings are next tested in an in vivo splinted rat excisional wound healing model. Histological analysis reveals that MACF+O2 dressings improve re-epithelialization (p<0.0001) and synthesis of collagen over controls (p<0.01). Analysis of endogenous metabolites in the wounds using global metabolomics demonstrates that MACF+O2 dressings promotes a regenerative metabolic process directed toward hydroxyproline and collagen synthesis, with confirmation of metabolite levels within this pathway. The results of this study confirm that increased oxygen delivery through the application of MACF+O2 hydrogels enhances wound healing and metabolomics analyses provides a powerful tool to assess wound healing physiology. STATEMENT OF SIGNIFICANCE: This work presents the first application of a novel class of oxygen delivering biomaterials (methacrylamide chitosan modified with perfluorocarbon chains (MACF)) as a hydrogel wound dressing. This manuscript also contains strong focus on the biochemical benefits of MACF dressings on underlying mechanisms vital to successful wound healing. In this vein, this manuscript presents the application of applied metabolomics (tandem mass spectroscopy) to uncover biomaterial interactions with wound healing mechanisms. We believe the approaches described in this manuscript will be of great interest to biomedical scientists and particularly to researchers studying wound healing, metabolomics, applied biomaterials and regenerative medicine.


Subject(s)
Acrylamides , Chitosan , Collagen/biosynthesis , Fluorocarbon Polymers , Hydrogels , Oxygen/metabolism , Wound Healing/drug effects , Wounds, Penetrating , Acrylamides/chemistry , Acrylamides/pharmacology , Animals , Chitosan/chemistry , Chitosan/pharmacology , Fluorocarbon Polymers/chemistry , Fluorocarbon Polymers/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Male , Rats , Rats, Wistar , Wounds, Penetrating/drug therapy , Wounds, Penetrating/metabolism
18.
ACS Appl Mater Interfaces ; 8(7): 4323-35, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26811936

ABSTRACT

Long-term (multiple-week or -month) release of small, water-soluble molecules from hydrogels remains a significant pharmaceutical challenge, which is typically overcome at the expense of more-complicated drug carrier designs. Such approaches are payload-specific and include covalent conjugation of drugs to base materials or incorporation of micro- and nanoparticles. As a simpler alternative, here we report a mild and simple method for achieving multiple-month release of small molecules from gel-like polymer networks. Densely cross-linked matrices were prepared through ionotropic gelation of poly(allylamine hydrochloride) (PAH) with either pyrophosphate (PPi) or tripolyphosphate (TPP), all of which are commonly available commercial molecules. The loading of model small molecules (Fast Green FCF and Rhodamine B dyes) within these polymer networks increases with the payload/network binding strength and with the PAH and payload concentrations used during encapsulation. Once loaded into the PAH/PPi and PAH/TPP ionic networks, only a few percent of the payload is released over multiple months. This extended release is achieved regardless of the payload/network binding strength and likely reflects the small hydrodynamic mesh size within the gel-like matrices. Furthermore, the PAH/TPP networks show promising in vitro cytocompatibility with model cells (human dermal fibroblasts), though slight cytotoxic effects were exhibited by the PAH/PPi networks. Taken together, the above findings suggest that PAH/PPi and (especially) PAH/TPP networks might be attractive materials for the multiple-month delivery of drugs and other active molecules (e.g., fragrances or disinfectants).


Subject(s)
Biocompatible Materials/chemistry , Drug Delivery Systems , Drug Liberation , Biocompatible Materials/therapeutic use , Chitosan/chemistry , Diphosphates/chemistry , Fibroblasts/drug effects , Humans , Hydrogels/chemistry , Hydrogels/therapeutic use , Polyamines/chemistry
19.
Indian J Radiol Imaging ; 24(1): 75-9, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24851010

ABSTRACT

Myositis ossificans is a rare cause of trismus. We present a case of pseudomalignant myositis ossificans involving medial pterygoid, lateral pterygoid, and temporalis muscles. Patient presented with gross limitation in mouth opening. There was no history of trauma. Computed tomography (CT) images revealed a bone density mass located in the region of medial and lateral pterygoid muscles on the right and temporalis muscle on the left. Magnetic resonance imaging (MRI) showed similar findings. Radiological diagnosis was pseudomalignant myositis ossificans. The masses were resected and histopathologic examination confirmed the above diagnosis. This report describes the characteristic CT and MRI features. The unique feature of this case is the absence of history of trauma with involvement of multiple masticatory muscles, which, to the best of our knowledge, has not been reported before.

20.
Indian Heart J ; 66(2): 216-9, 2014.
Article in English | MEDLINE | ID: mdl-24814120

ABSTRACT

We report a case of very late stent thrombosis 7 years post sirolimus eluting stent implantation presenting as ST elevation MI while on dual antiplatelet therapy. Angiography revealed an aneurysm at the proximal end of the stent. The patient was managed successfully by primary percutaneous coronary intervention (PCI) with adjunct thrombus aspiration and intracoronary abciximab administration followed by deploying a mesh-covered stent MGuard. This very late complication is a rare presentation after a drug illuting stent (DES).


Subject(s)
Angioplasty, Balloon, Coronary/instrumentation , Coronary Aneurysm/therapy , Coronary Disease/therapy , Drug-Eluting Stents/adverse effects , Prosthesis Failure , Thrombosis/diagnosis , Angioplasty, Balloon, Coronary/methods , Coronary Aneurysm/diagnostic imaging , Coronary Aneurysm/etiology , Coronary Angiography/methods , Coronary Disease/diagnostic imaging , Device Removal , Follow-Up Studies , Humans , Male , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Rare Diseases , Retreatment/methods , Risk Assessment , Sirolimus/pharmacology , Thrombosis/etiology , Thrombosis/therapy , Time Factors , Treatment Outcome
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