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1.
Pharm Res ; 41(6): 1183-1199, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38849712

ABSTRACT

AIM: This study aimed to fabricate dexamethasone sodium phosphate loaded microneedle arrays (MNA) and investigate their efficiency in combination with iontophoresis for the treatment of hind paw oedema in rats. METHODS: Drug loaded polyvinyl alcohol, polyvinyl pyrrolidone and D-sorbitol-based MNA11 were fabricated by vacuum micromolding. Physicochemical, morphological, thermal, in-silico, in-vitro insertion ability (on parafilm) and drug release studies were performed. Ex-vivo permeation, in-vivo insertion and anti-inflammatory studies were performed in combination with iontophoresis. RESULTS: MNA11 displayed sharp-tipped projections and acceptable physicochemical features. Differential scanning calorimetry results indicated that drug loaded MNA11 were amorphous solids. Drug interacted with PVP and PVA predominately via hydrogen bonding. Parafilm displayed conspicuously engraved complementary structure of MNA11. Within 60 min, 91.50 ± 3.1% drug released from MNA11. A significantly higher i.e., 95.06 ± 2.5% permeation of drug was observed rapidly (within 60 min) from MNA11-iontophoresis combination than MNA11 i.e., 84.07 ± 3.5% within 240 min. Rat skin treated using MNA11 and MNA11-iontophoresis showed disruptions / microchannels in the epidermis without any damage to underlying anatomical structures. MNA11-iontophoresis combination led to significant reduction (83.02 ± 3.9%) in paw oedema as compared to MNA11 alone (72.55 ± 4.1%). CONCLUSION: MNA11-iontophoresis combination can act as a promising candidate to deliver drugs transcutaneously for treating inflammatory diseases.


Subject(s)
Administration, Cutaneous , Anti-Inflammatory Agents , Dexamethasone , Drug Delivery Systems , Edema , Iontophoresis , Needles , Skin Absorption , Skin , Animals , Iontophoresis/methods , Dexamethasone/administration & dosage , Dexamethasone/pharmacokinetics , Dexamethasone/analogs & derivatives , Rats , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/pharmacokinetics , Edema/drug therapy , Drug Delivery Systems/methods , Skin/metabolism , Skin/drug effects , Male , Drug Liberation , Inflammation/drug therapy , Rats, Sprague-Dawley
2.
Prostaglandins Other Lipid Mediat ; 171: 106806, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38185280

ABSTRACT

Bacterial endophthalmitis is a blinding infectious disease typically acquired during ocular surgery. We previously reported significant alterations in retinal metabolism during Staphylococcus (S) aureus endophthalmitis. However, the changes in retinal lipid composition during endophthalmitis are unknown. Here, using a mouse model of S. aureus endophthalmitis and an untargeted lipidomic approach, we comprehensively analyzed temporal alterations in total lipids and oxylipin in retina. Our data showed a time-dependent increase in the levels of lipid classes, sphingolipids, glycerolipids, sterols, and non-esterified fatty acids, whereas levels of phospholipids decreased. Among lipid subclasses, phosphatidylcholine decreased over time. The oxylipin analysis revealed increased prostaglandin-E2, hydroxyeicosatetraenoic acids, docosahexaenoic acid, eicosapentaenoic acid, and α-linolenic acid. In-vitro studies using mouse bone marrow-derived macrophages showed increased lipid droplets and lipid-peroxide formation in response to S. aureus infection. Collectively, these findings suggest that S. aureus-infection alters the retinal lipid profile, which may contribute to the pathogenesis of bacterial endophthalmitis.


Subject(s)
Endophthalmitis , Staphylococcus aureus , Humans , Staphylococcus aureus/physiology , Lipidomics , Oxylipins , Endophthalmitis/microbiology , Endophthalmitis/pathology , Retina/pathology
3.
Cell Mol Life Sci ; 80(10): 309, 2023 Sep 28.
Article in English | MEDLINE | ID: mdl-37770649

ABSTRACT

Bacterial endophthalmitis is a severe complication of eye surgeries that can lead to vision loss. Current treatment involves intravitreal antibiotic injections that control bacterial growth but not inflammation. To identify newer therapeutic targets to promote inflammation resolution in endophthalmitis, we recently employed an untargeted metabolomics approach. This led to the discovery that the levels of S-nitroso-L-glutathione (GSNO) were significantly reduced in an experimental murine Staphylococcus aureus (SA) endophthalmitis model. In this study, we tested the hypothesis whether GSNO supplementation via different routes (oral, intravitreal) provides protection during bacterial endophthalmitis. Our results show that prophylactic administration of GSNO via intravitreal injections ameliorated SA endophthalmitis. Therapeutically, oral administration of GSNO was found to be most effective in reducing intraocular inflammation and bacterial burden. Moreover, oral GSNO treatment synergized with intravitreal antibiotic injections in reducing the severity of endophthalmitis. Furthermore, in vitro experiments using cultured human retinal Muller glia and retinal pigment epithelial (RPE) cells showed that GSNO treatment reduced SA-induced inflammatory mediators and cell death. Notably, both in-vivo and ex-vivo data showed that GSNO strengthened the outer blood-retinal barrier during endophthalmitis. Collectively, our study demonstrates GSNO as a potential therapeutic agent for the treatment of intraocular infections due to its dual anti-inflammatory and cytoprotective properties.


Subject(s)
Endophthalmitis , Eye Infections, Bacterial , Staphylococcal Infections , Mice , Humans , Animals , Disease Models, Animal , Endophthalmitis/drug therapy , Endophthalmitis/microbiology , Staphylococcal Infections/drug therapy , Inflammation/drug therapy , Staphylococcus aureus , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Glutathione , Eye Infections, Bacterial/drug therapy , Eye Infections, Bacterial/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Administration, Oral
4.
Pharm Res ; 40(8): 2039-2049, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37186072

ABSTRACT

AIM: This study was aimed to develop rabies vaccine incorporated microneedle (MN) patches and evaluate the immunogenicity of prepared formulations in combination with iontophoresis. METHODS: Patches comprising of polyvinyl pyrrolidone, hyaluronic acid and polyethylene glycol 400 were engineered by vacuum micromolding technique. Physical evaluation of patches included determination of folding endurance, % swelling and morphological features. In vitro release study was performed in skin simulant agarose gel using model drug (methylene blue) loaded patches. In vitro insertion ability was assessed using stratum corneum simulant parafilm. In vivo insertion study was performed in rats. Immunogenicity was evaluated in dogs by determining immunoglobulin G (IgG) and rabies virus neutralizing antibodies (RVNA) titer. RESULTS: Patches displayed uniformly distributed microprojections with pointed tips and smooth surface, ~ 70% swelling, remained intact for ~ 200 foldings and successfully penetrated the parafilm. The area covered by model drug across agarose gel was almost double following treatment with MN-iontophoresis combination (MNdi) compared to MN alone (MNdo). Histological examination of rat skin treated with vaccine laden MN (MNvo) and MN-iontophoresis combination (MNvi) confirmed the formation of grooves in epidermis without any damage to the deep vasculature. A ~ 73% and ~ 206% increase (compared to untreated counterpart) was observed in the IgG titer of MNvo and MNvi treated dogs, respectively. The RVNA titer was increased by ~ 1.2 and ~ 2.2 times (compared to threshold value) after MNvo and MNvi treatment, respectively. CONCLUSION: MN-iontophoresis combination provided relatively potent immunogenic response over the conventional intramuscular injection, hence, can be used for administering vaccines transcutaneously.


Subject(s)
Rabies Vaccines , Rats , Animals , Dogs , Iontophoresis/methods , Paraffin , Sepharose , Administration, Cutaneous , Skin , Drug Delivery Systems , Needles , Immunoglobulin G
5.
Physiol Plant ; 175(6): e14057, 2023.
Article in English | MEDLINE | ID: mdl-38148196

ABSTRACT

Climate change-induced concurrent drought and salinity stresses significantly threaten global crop yields, yet the physio-biochemical responses to combined stress in quinoa remain elusive. This study evaluated quinoa responses under four growth conditions: well-watered, drought stress, salt stress, and drought + salt stress with (15 mM) or without (0 mM) exogenous hydrogen peroxide (H2 O2 ) application. All examined stresses (alone or in combination) reduce quinoa growth and net photosynthesis, although salt stress was found to be less destructive than drought and combined stress. Strikingly, superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), stomatal conductance (gs ), photosynthetic rate (PN ), K+ uptake, shoot height, shoot fresh, and dry weight were increased by 46.1%, 22.2%, 101.6%, 12.9%, 12.1%, 22.4%, 7.1%, 14%, and 16.4%, respectively, under combined stress compared to drought alone. In addition, exogenous H2 O2 effectively improved gaseous exchange, osmolytes' accumulation, and antioxidant activity, resulting in reduced lipid peroxidation, which eventually led to higher plant growth under all coercive conditions. The principle component analysis (PCA) indicated a strong positive correlation between antioxidant enzymes and inorganic ions, which contributed efficiently to osmotic adjustment, particularly under conditions of salinity followed by combined stress. In short, in combination, salt stress has the potential to mitigate drought-induced injuries by promoting the absorption of inorganic solutes for osmoregulation in quinoa plants. Furthermore, exogenous application of H2 O2 could be opted to enhance quinoa performance to increase its tolerance mechanism against drought and salinity, even under combined stress.


Subject(s)
Antioxidants , Chenopodium quinoa , Antioxidants/metabolism , Osmoregulation , Salinity , Droughts , Gases
6.
Proc Natl Acad Sci U S A ; 117(43): 26672-26680, 2020 Oct 27.
Article in English | MEDLINE | ID: mdl-33037154

ABSTRACT

Dendrite-free electrodeposition of lithium metal is necessary for the adoption of high energy-density rechargeable lithium metal batteries. Here, we demonstrate a mechanism of using a liquid crystalline electrolyte to suppress dendrite growth with a lithium metal anode. A nematic liquid crystalline electrolyte modifies the kinetics of electrodeposition by introducing additional overpotential due to its bulk-distortion and anchoring free energy. By extending the phase-field model, we simulate the morphological evolution of the metal anode and explore the role of bulk-distortion and anchoring strengths on the electrodeposition process. We find that adsorption energy of liquid crystalline molecules on a lithium surface can be a good descriptor for the anchoring energy and obtain it using first-principles density functional theory calculations. Unlike other extrinsic mechanisms, we find that liquid crystals with high anchoring strengths can ensure smooth electrodeposition of lithium metal, thus paving the way for practical applications in rechargeable batteries based on metal anodes.

7.
Pak J Pharm Sci ; 36(3(Special)): 941-946, 2023 May.
Article in English | MEDLINE | ID: mdl-37587702

ABSTRACT

The current research investigation demonstrated that the aqueous leaves extract of Rosamarinus officinalis possesses cardinal phyto-chemicals to fabricate AgNPs in an eco-friendly way. The phyto-synthesized AgNPs were characterized to be stable, monodispersed, polycrystalline and mostly spheroidal in conformation. The nano-spheriods were observed to be 25-75 nm in diameter, displaying λmax peak at 430 nm. From the comparative antimicrobial investigations, it was observed that AgNPs manifested tremendous bactericidal properties against all test organisms particularly S. epidermis (89%), S. aureus (84%) and K. pneumonia (84%), owing least MIC values of 40µL. The aced fungicidal activity was also exhibited by AgNPs against all fungal test species particularly C. herbarum (90%), A. flavus (85%), R. stolonifer (85%) and C. jadinii (85%). In contrast to AgNPs, all crude ethanolic, aqueous, methanolic and n-hexanoic extracts manifested less to moderate antimicrobial activity against all test micro-organisms with three-fold escalating MIC values i.e., 160µL.


Subject(s)
Anti-Infective Agents , Metal Nanoparticles , Silver/pharmacology , Staphylococcus aureus , Anti-Infective Agents/pharmacology , Plant Leaves , Plant Extracts/pharmacology
8.
J Contemp Dent Pract ; 23(12): 1255-1259, 2022 Dec 01.
Article in English | MEDLINE | ID: mdl-37125524

ABSTRACT

AIM: This study explores the demineralizing potential of the combination of chitosan with nanohydroxyapatite (n-HA) and self-assembling peptides with n-HA. MATERIALS AND METHODS: A total of 66 first premolar teeth of similar dimensions extracted for orthodontic purposes were collected for this study. These were then demineralized and randomly divided into the following three groups (n = 22): (i) Control group, (ii) n-HA + Chitosan (HAC), and (iii) self-assembling peptide + n-HA (SP-HA). The samples in each group were brushed every 24 hours with the respective agent. The specimens were stored in Fusayama Meyer's artificial saliva at room temperature and the solution was replenished daily. Mineral content (Ca, P) and surface morphology of the specimens was analyzed, using scanning electron microscopy and energy dispersion X-ray spectroscopy (SEM-EDAX), before demineralization, at 15 days of remineralization and 30 days of remineralization. A two-way analysis of variance (ANOVA) test followed by Tukey's honest significant difference (HSD) post hoc analysis was used to compare the mean elemental composition of the different groups (p < 0.05). RESULTS: There was no significant difference in the calcium (Ca) and phosphate (P) weight percentage between the different groups at the baseline and after demineralization. The Ca and P weight percentages of all three groups after remineralization for 15 and 30 days showed no significant difference from the baseline or after demineralization. The surface morphology after 15 days of remineralization therapy showed decreased surface porosity and increased mineral deposition in the HAC group than the HP-SA group. Surface morphology after 30 days of remineralization showed a more homogenous and smoother surface in the HAC group than the HP-SA group. CONCLUSION: From the results of this study, it can be concluded that the combination of chitosan with n-HA and self-assembling peptides with n-HA can be considered effective demineralizing agents. CLINICAL SIGNIFICANCE: Considering the non-invasive nature of remineralization therapy understanding the effectiveness of different agents is of utmost importance. The demineralizing properties of chitosan, n-HA and self-assembling peptides make their combinations ideal for studying their effectiveness in treating white spot lesions.


Subject(s)
Chitosan , Tooth Demineralization , Humans , Calcium , Chitosan/therapeutic use , Dental Enamel , Minerals , Peptides/therapeutic use , Tooth Demineralization/drug therapy , Tooth Remineralization/methods
9.
Nat Mater ; 19(7): 758-766, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32341510

ABSTRACT

Dendrite formation during electrodeposition while charging lithium metal batteries compromises their safety. Although high-shear-modulus (Gs) solid-ion conductors (SICs) have been prioritized to resolve the pressure-driven instabilities that lead to dendrite propagation and cell shorting, it is unclear whether these or alternatives are needed to guide uniform lithium electrodeposition, which is intrinsically density-driven. Here, we show that SICs can be designed within a universal chemomechanical paradigm to access either pressure-driven dendrite-blocking or density-driven dendrite-suppressing properties, but not both. This dichotomy reflects the competing influence of the SIC's mechanical properties and the partial molar volume of Li+ ([Formula: see text]) relative to those of the lithium anode (GLi and VLi) on plating outcomes. Within this paradigm, we explore SICs in a previously unrecognized dendrite-suppressing regime that are concomitantly 'soft', as is typical of polymer electrolytes, but feature an atypically low [Formula: see text] that is more reminiscent of 'hard' ceramics. Li plating (1 mA cm-2; T = 20 °C) mediated by these SICs is uniform, as revealed using synchrotron hard X-ray microtomography. As a result, cell cycle life is extended, even when assembled with thin Li anodes (~30 µm) and either high-voltage NMC-622 cathodes (1.44 mAh cm-2) or high-capacity sulfur cathodes (3.02 mAh cm-2).

10.
Invest New Drugs ; 39(3): 636-643, 2021 06.
Article in English | MEDLINE | ID: mdl-33230623

ABSTRACT

In order to suppress 5' cap-mediated translation a highly available inhibitor of the interaction between the 5' mRNA cap and the eIF4E complex has been developed. 4Ei-10 is a member of the class of ProTide compounds and has elevated membrane permeability and is a strong active chemical antagonist for eIF4E. Once taken up by cells it is converted by anchimeric activation of the lipophilic 2-(methylthio) ethyl protecting group and after that Hint1 P-N bond cleavage to N7-(p-chlorophenoxyethyl) guanosine 5'-monophosphate (7-Cl-Ph-Ethyl-GMP). Using this powerful interaction, it has been demonstrated that 4Ei-10 inhibits non-small cell lung cancer (NSCLC) cell growth. In addition, treatment of NSCLC cells with 4Ei-10 results in suppression of translation and diminished expression of a cohort of cellular proteins important to maintaining the malignant phenotype and resisting apoptosis such as Bcl-2, survivin, and ornithine decarboxylase (ODC). Finally, as a result of targeting the translation of anti-apoptotic proteins, NSCLC cells are synergized to be more sensitive to the existing anti-neoplastic treatment gemcitabine currently used in NSCLC therapy.


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Eukaryotic Initiation Factor-4E , Lung Neoplasms , Nucleotides , Prodrugs , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/drug therapy , Cell Line, Tumor , Cell Survival/drug effects , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Drug Interactions , Eukaryotic Initiation Factor-4E/antagonists & inhibitors , Lung Neoplasms/drug therapy , Prodrugs/pharmacology , Nucleotides/pharmacology , Nucleotides/therapeutic use , Gemcitabine
11.
Mol Cell Biochem ; 476(11): 4133-4137, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34312783

ABSTRACT

Chronic kidney disease (CKD) is a renal dysfunction that can lead to high rates of mortality and morbidity, particularly when coupled with late diagnosis. CKD has become a major health problem due to its challenging detection at early stages when clear symptoms are yet to be presented. Thus, CKD is likely to be identified when the substantive conditions of the disease are manifest. In order to address the development of the disease and provide necessary treatments at the initial stage, the investigation of new biomarkers and metabolites associated with early detection of CKD are needed. Identified metabolites could be used to confirm the presence of the disease, obtain information on its mechanism and facilitate the development of novel pharmaceutical treatments. Such metabolites may be detected from biofluids and tissues using a range of analytical techniques. There are a number of metabolites that have been identified by mass spectrometry at high sensitivities, whilst the detection of metabolites directly from biofluids using NMR could present a more rapid way to expand our understanding of this disease. This review is focused on NMR-based metabolomics associated with CKD in humans and animals.


Subject(s)
One Health , Renal Insufficiency, Chronic/diagnosis , Animals , Biomarkers/analysis , Early Diagnosis , Humans , Magnetic Resonance Spectroscopy/methods , Mass Spectrometry/methods , Metabolomics/methods , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/therapy
12.
Pharm Res ; 38(1): 165-177, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33534130

ABSTRACT

AIM: The aim of this study was to fabricate polymeric microneedles, loaded with macrolides (erythromycin, azithromycin), using hyaluronic acid and polyvinyl pyrollidone. METHODS: These microneedles were fabricated using a vacuum micromolding technique. The integrity of the microneedle patches was studied by recording their morphologic features, folding endurance, swelling and micro-piercing. Physicochemical characteristics were studied by differential scanning calorimetry, thermogravimetric analysis and fourier transform infrared spectroscopy. In-vitro drug release, antibiofilm and effect of microneedle patch on wound healing were also studied to confirm the efficacy of the formulations. RESULTS: Formulated patches displayed acceptable folding endurance (>100) and uniform distribution of microneedles (10 × 10) that can penetrate parafilm. Differential scanning calorimetry results depict a decrease in the crystallinity of macrolides following their incorporation in to a polymer matrix. Percentage release of azithromycin and erythromycin from the polymeric patch formulations (over 30 min) was 90% and 63% respectively. Broadly, the zone of bacterial growth inhibition follows the same order for Staphylococcus aureus, Escherichia coli and Salmonella enterica. After 5 days of treatment with azithromycin patches, the wound healing was complete and skin structure (e.g. hair follicles and dermis) was regenerated. CONCLUSION: It was concluded that azithromycin loaded microneedle patches can be used to treat biofilms in the infected wounds.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Biofilms/drug effects , Drug Delivery Systems/methods , Wound Healing/drug effects , Wound Infection/drug therapy , Administration, Cutaneous , Animals , Anti-Bacterial Agents/pharmacokinetics , Azithromycin/administration & dosage , Azithromycin/pharmacokinetics , Disease Models, Animal , Drug Liberation , Erythromycin/administration & dosage , Erythromycin/pharmacokinetics , Escherichia coli/drug effects , Humans , Male , Microbial Sensitivity Tests , Rats , Salmonella enterica/drug effects , Skin/injuries , Skin/metabolism , Skin/microbiology , Staphylococcus aureus/drug effects , Transdermal Patch , Wound Infection/microbiology
13.
Molecules ; 26(21)2021 Oct 30.
Article in English | MEDLINE | ID: mdl-34770985

ABSTRACT

BACKGROUND: Periodontitis is characterized by excessive osteoclastic activity, which is closely associated with inflammation. It is well established that MAPK/NF-kB axis is a key signaling pathway engaged in osteoclast differentiation. It is stated that that biphasic calcium phosphate (BCP) and platelet-rich fibrin (PRF) have significant antiostoeclastogenic effects in chronic periodontitis. OBJECTIVE: We aimed to elucidate the synergetic effect of PRF/BCP involvement of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and the mitogen-activated protein kinase (MAPK) signaling pathway in osteoclast differentiation in chronic periodontitis. METHODS: We induced osteoclast differentiation in vitro using peripheral blood mononuclear cells (PBMCs) derived from patients with chronic periodontitis. We assessed osteoclast generation by tartrate-resistant acid phosphatase (TRAP) activity, proinflammatory cytokines were investigated by ELISA and NF-κB, and IKB by immunoblot, respectively. MAPK proteins and osteoclast transcription factors were studied by Western blot analysis and osteoclast transcriptional genes were assessed by RT-PCR. RESULTS: The results showed that the potent inhibitory effect of PRF/BCP on osteoclastogenesis was evidenced by decreased TRAP activity and the expression of transcription factors, NFATc1, c-Fos, and the osteoclast marker genes, TRAP, MMP-9, and cathepsin-K were found to be reduced. Further, the protective effect of PRF/BCP on inflammation-mediated osteoclastogenesis in chronic periodontitis was shown by decreased levels of proinflammatory cytokines, NF-kB, IKB, and MAPK proteins. CONCLUSIONS: PRF/BCP may promote a synergetic combination that could be used as a strong inhibitor of inflammation-induced osteoclastogenesis in chronic periodontitis.


Subject(s)
Chronic Periodontitis/drug therapy , Hydroxyapatites/pharmacology , Inflammation/drug therapy , NF-kappa B/antagonists & inhibitors , Platelet-Rich Fibrin/metabolism , Adult , Biomarkers/metabolism , Cell Differentiation/drug effects , Chronic Periodontitis/metabolism , Female , Humans , Inflammation/metabolism , MAP Kinase Signaling System/drug effects , Male , Middle Aged , NF-kappa B/metabolism , Osteoclasts/drug effects , Osteoclasts/metabolism
14.
AAPS PharmSciTech ; 22(1): 23, 2021 Jan 05.
Article in English | MEDLINE | ID: mdl-33400042

ABSTRACT

Cannabidiol (CBD) and cannabigerol (CBG) are two active pharmaceutical ingredients, derived from cannabis plant. In the present study, CBD and CBG were formulated with polyvinyl(pyrrolidone) (PVP) and Eudragit L-100, using electrohydrodynamic atomization (electrospinning). The produced fibers were smooth and uniform in shape, with average fiber diameters in the range of 700-900 nm for PVP fibers and 1-5 µm for Eudragit L-100 fibers. The encapsulation efficiency for both CB and CBG was high (over 90%) for all formulations tested. Both in vitro release and disintegration tests of the formulations in simulated gastric fluids (SGF) and simulated intestinal fluids (SIF) indicated the rapid disintegration and dissolution of the fibers and the subsequent rapid release of the drugs. The study concluded that the electrospinning process is a fast and efficient method to produce drug-loaded fibers suitable for the per os administration of cannabinoids.


Subject(s)
Cannabidiol/administration & dosage , Cannabinoids/administration & dosage , Nanofibers/chemistry , Administration, Oral , Cannabidiol/chemistry , Cannabinoids/chemistry , Drug Compounding , Drug Liberation , Polymethacrylic Acids/chemistry , Povidone/chemistry
15.
Pak J Med Sci ; 37(5): 1440-1444, 2021.
Article in English | MEDLINE | ID: mdl-34475927

ABSTRACT

OBJECTIVES: To compare safety and number of post-operative visits of patients in convenient day versus conventional first day follow-up after phacoemulsification. METHODS: This observational cohort study was conducted in Department of ophthalmology, Sahiwal Medical College, Sahiwal from November 2019 to August 2020. There were 600 patients who underwent uncomplicated phacoemulsification with intraocular lens implantation. Patients were allocated into two groups. Group-I comprised of patients with convenient day follow-up during the first post-operative week. Group-II comprised of the patients with conventional first day follow-up. Rate of complications, number of visits during the first month and final visual acuity were recorded. RESULTS: In Group-I post-operative complications were noted in 12.67% cases on first follow up visit and in 2.67% cases on first month follow up visit. In Group-II post-operative complication were noted in 22 % cases on first follow up visit and in 4% cases on first month follow up visit. Common postoperative complications were corneal oedema, anterior segment intraocular inflammation, residual lens matter in anterior chamber and intraocular lens subluxation. There was no difference in presenting and postoperative visual acuity between the two groups. Mean follow-up visits were 2.23 ± 0.42 in Group-I and 3.55 ± 0.50 in Group-II. CONCLUSION: Convenient day follow-up is as safe as conventional first day follow-up. Convenient day follow-up significantly reduces the number of post-operative visits. This would translate into cost reduction both for the patients and the health care facility.

16.
Proc Natl Acad Sci U S A ; 114(1): 57-61, 2017 01 03.
Article in English | MEDLINE | ID: mdl-27994136

ABSTRACT

Most next-generation Li ion battery chemistries require a functioning lithium metal (Li) anode. However, its application in secondary batteries has been inhibited because of uncontrollable dendrite growth during cycling. Mechanical suppression of dendrite growth through solid polymer electrolytes (SPEs) or through robust separators has shown the most potential for alleviating this problem. Studies of the mechanical behavior of Li at any length scale and temperature are limited because of its extreme reactivity, which renders sample preparation, transfer, microstructure characterization, and mechanical testing extremely challenging. We conduct nanomechanical experiments in an in situ scanning electron microscope and show that micrometer-sized Li attains extremely high strengths of 105 MPa at room temperature and of 35 MPa at 90 °C. We demonstrate that single-crystalline Li exhibits a power-law size effect at the micrometer and submicrometer length scales, with the strengthening exponent of -0.68 at room temperature and of -1.00 at 90 °C. We also report the elastic and shear moduli as a function of crystallographic orientation gleaned from experiments and first-principles calculations, which show a high level of anisotropy up to the melting point, where the elastic and shear moduli vary by a factor of ∼4 between the stiffest and most compliant orientations. The emergence of such high strengths in small-scale Li and sensitivity of this metal's stiffness to crystallographic orientation help explain why the existing methods of dendrite suppression have been mainly unsuccessful and have significant implications for practical design of future-generation batteries.

17.
Drug Dev Ind Pharm ; 46(6): 963-974, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32363953

ABSTRACT

Development of drug products from natural sources enable advantageous treatment and therapy options. Bioactive compounds in Ganoderma lucidum spore powder (GLSP) are known for vast antibacterial, antioxidant and anti-cancer properties. Herein, we studied the use of dual-probe ultrasound to extract triterpenoids from GLSP and further investigated the bioactivity of resulting products. FTIR results confirm the presence of key peaks although dual-probe ultrasound varied extraction efficacy. Response surface methodology (RSM) was used to optimize extraction conditions (55:28 for solvent to solid ratio, 10.38 s of ultrasound time and 94% v/v of ethanol concentration). HPLC-Q-TOF-MS confirmed the presence of nine different compounds and in vitro tests confirm good biocompatibility. Extracts are shown to inhibit DPPH radicals, reaching a maximum (61.09 ± 1.38%) at triterpenoid concentrations of 600 µg/mL. Dual-mode assisted extraction provides an enhanced approach for active embedded fiber production on a scale favorable to industry when using optimized process parameters. Furthermore, triterpenoid extracts show antibacterial properties on Staphylococcus aureus and Escherichia coli with potential in antibacterial and anticancer applications.


Subject(s)
Reishi , Triterpenes , Powders , Sonication/methods , Spores
18.
Prep Biochem Biotechnol ; 50(3): 302-315, 2020.
Article in English | MEDLINE | ID: mdl-31755817

ABSTRACT

When ingested as a dietary supplement, Ganoderma lucidum spore powders (GLSP) provide various health benefits such as enhanced immunity, liver protection and anti-cancer effects. In this study, triterpenoid extraction from GLSP was achieved using an ultrasound-assisted process which was optimized using response surface methodology (RSM). Ultrasound-assisted extraction (UAE) was also compared to the most conventional chemical extraction method. For UAE, optimum extraction conditions were found to be ethanol concentration = 95% v/v; solvent to solid ratio = 50:1 mL/g; ultrasound time = 5.4 min; ultrasound power = 564.7 w, and ultrasound probe distance = 8.2 cm. At optimal UAE conditions, no significant differences were found between experimental (0.97 ± 0.04 %) and predicted values (99%); which indicates appreciable correlation at the 97% confidence interval. The findings show the application of Box-Behnken design (BBD) to predict and optimize triterpenoid yield for UAE of triterpenoid from GLSP. Furthermore, glucose consumption was 2.68 times that of control samples when tested with insulin-resistant HepG2 cell, showing potential use in type 2 diabetes. In addition, triterpenoid extracts show good biocompatibility and inhibition of antioxidant activity.


Subject(s)
Reishi/chemistry , Spores, Fungal/chemistry , Triterpenes , Ultrasonic Waves , Triterpenes/chemistry , Triterpenes/isolation & purification
19.
Pharm Dev Technol ; 25(2): 197-205, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31638453

ABSTRACT

The purpose of this study was to investigate the application of piezoelectric inkjet technology in the preparation of custom-made indomethacin (IMC) films. Indomethacin solutions with and without PVP were printed onto polymeric sheets using a commercial inkjet printer. Drug loading was varied by selecting a machine parameter different dots per inches (DPIs). The printed patches were evaluated for particulate morphologies, drug loading, in vitro release and ex vivo skin permeation and anti-inflammatory effects using hind paw inflammation model. Calculated drug loaded in 2 × 2 cm2 patches of IMC of 96, 300, and 600 DPIs were in the range of 40, 60, and 65 µg, respectively. Patches loaded with IMC alcoholic solution showed crystalline structures observed by scanning electron microscopy and the addition of PVP in solution turned it to amorphous form. The drug release profile showed 60-70% of total drug released in 3 h. Permeation studies showed 40-50% of total drug loaded permeated through rat skin using Franz cells. Patches with higher printing density 600 DPI showed anti-inflammatory effect in hind paw inflammation model studies. This study has shown the potential of personalized medicine in which a calculated amount of drug can be delivered to patients by piezoelectric technology.


Subject(s)
Indomethacin/chemistry , Animals , Chemistry, Pharmaceutical/methods , Drug Delivery Systems/methods , Drug Liberation/drug effects , Excipients/chemistry , Female , Indomethacin/pharmacology , Inflammation/drug therapy , Male , Polymers/chemistry , Precision Medicine/methods , Printing, Three-Dimensional , Rats , Skin/drug effects
20.
J Pak Med Assoc ; 69(9): 1390-1393, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31511733

ABSTRACT

Chromoblastomycosis is a chronic fungal infection of the subcutaneous tissue. The infection usually results from a traumatic injury and inoculation of the microorganism by a specific group of dematiaceous fungi, resulting in the formation of verrucous plaques. The fungi produce sclerotic or medlar bodies (also called muriform bodies or sclerotic cells) seen on direct microscopic examination of skin smears. The disease is often found in adults due to trauma. We report a case of chromoblastomycosis in a 12-year-old child in whom the infection started when he was only 4 years old with secondary involvement of bones, cartilage, tongue and palatine tonsils. The child was not immunosuppressed.


Subject(s)
Bone Diseases, Infectious/diagnostic imaging , Chromoblastomycosis/diagnosis , Invasive Fungal Infections/diagnosis , Staphylococcal Infections/diagnosis , Anti-Bacterial Agents/therapeutic use , Bone Diseases, Infectious/drug therapy , Carbaryl/therapeutic use , Child , Chromoblastomycosis/diagnostic imaging , Chromoblastomycosis/drug therapy , Finger Joint/diagnostic imaging , Humans , Invasive Fungal Infections/diagnostic imaging , Invasive Fungal Infections/drug therapy , Lymphadenopathy/diagnosis , Male , Metatarsophalangeal Joint/diagnostic imaging , Methicillin-Resistant Staphylococcus aureus , Palatine Tonsil , Pharyngeal Diseases/diagnosis , Pharyngeal Diseases/drug therapy , Staphylococcal Infections/drug therapy
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