Transcutaneous Delivery of Dexamethasone Sodium Phosphate Via Microneedle-Assisted Iontophoretic Enhancement - A Potential Therapeutic Option for Inflammatory Disorders.

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.

Streptomyces enissocaesilis L-82 has broad-spectrum antibacterial activity and promotes growth for Carassius auratus.

Aeromonas is the main pathogen causing bacterial diseases in fish. The disadvantages of chemical drugs to control fish diseases have been highlighted, and it is urgent to find an eco-friendly control method. In this study, an actinomycete strain with antibacterial activity against fish pathogenic bacteria was screened from soil samples. Combined with morphological characteristics, physiological and biochemical characteristics, and gyrB gene and whole genome comparison analysis, it was identified as a new strain of Streptomyces enissocaesilis, named Streptomyces enissocaesilis L-82. The strain has broad-spectrum antibacterial activity against fish pathogens. A substance with a mass-to-charge ratio of 227.20 [M + H] + was isolated and purified by high-performance liquid chromatography and mass spectrometry. It was presumed to be a derivative of 5-dimethylallylindole-3-acetonitrile. The strain is safe and non-toxic to crucian carp, and can stably colonize crucian carp and inhibit the proliferation of A. hydrophila. After feeding the feed containing 1 × 108 CFU/mL strain concentration, the weight growth rate and specific growth rate of crucian carp increased, the activity of ACP and SOD in serum increased, and the survival rate of crucian carp increased after challenge. Genome-wide analysis showed that the strain had strong ability to metabolize and tolerate extreme environments. And has a strong potential for disease resistance. Therefore, the strain is expected to be developed as a feed additive for fish farming. KEY POINTS: • The new Streptomyces enissocaesilis L-82 has a broad spectrum and stable antibacterial activity and meets the safety standards of feed additives. • Strain L-82 can colonize crucian carp, improve the growth, antioxidant, and immune performance of the host, and improve the survival rate after being infected with A. hydrophila. • Genome-wide analysis suggests that the strain has great disease resistance potential and is expected to be developed as a feed additive for fish culture.

Biochemical Perspectives on Natural Products in Wound Healing: Exploring Phytochemicals in Tissue Repair and Scar Prevention.

Wound healing is a critical process in tissue repair following injury, and traditional herbal therapies have long been utilized to facilitate this process. This review delves into the mechanistic understanding of the significant contribution of pharmacologically demonstrated natural products in wound healing. Natural products, often perceived as complex yet safely consumed compared to synthetic chemicals, play a crucial role in enhancing the wound-healing process. Drawing upon a comprehensive search strategy utilizing databases such as PubMed, Scopus, Web of Science, and Google Scholar, this review synthesizes evidence on the role of natural products in wound healing. While the exact pharmacological mechanisms of secondary metabolites in wound healing remain to be fully elucidated, compounds from alkaloids, phenols, terpenes, and other sources are explored here to delineate their specific roles in wound repair. Each phytochemical group exerts distinct actions in tissue repair, with some displaying multifaceted roles in various pathways, potentially enhancing their therapeutic value, supported by reported safety profiles. Additionally, these compounds exhibit promise in the prevention of keloids and scars. Their potential alongside economic feasibility may propel them towards pharmaceutical product development. Several isolated compounds, from natural sources, are undergoing investigation in clinical trials, with many reaching advanced stages.

Biochemical, Toxicological, and in Silico Aspects of Trillium govanianum Wall. ex D.Don (Trilliaceae): A Rich Source of Natural Bioactive Compounds.

Trillium govanianum is a high-value medicinal herb, having multifunctional traditional and culinary uses. The present investigation was carried out to evaluate the phytochemical, biological and toxicological parameters of the T. govanianum Wall. ex D. Don (Family: Trilliaceae) roots collected from Azad Kashmir, Pakistan. Phytochemical profiling was achieved by determining total bioactive contents (total phenolic and flavonoid contents) and UHPLC-MS analysis. For biological evaluation, antioxidant activities (DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation assays) and enzyme inhibition activities (against AChE, BChE, glucosidase, amylase, and tyrosinase) were performed. Moreover, cytotoxicity was assessed against three human carcinoma cell lines (MDA-MB-231, CaSki, and DU-145). The tested extract was found to contain higher total phenolics (7.56 mg GAE/g dry extract) as compared to flavonoid contents (0.45 mg RE/g dry extract). Likewise, for the antioxidant activity, higher CUPRAC activity was noted with 39.84 mg TE/g dry extract values. In the case of enzyme assays, higher activity was pointed out against the cholinesterase, glucosidase and tyrosinase enzymes. The plant extract displayed significant cytotoxicity against the cell lines examined. Moreover, the in-silico studies highlighted the interaction between the important phytochemicals and tested enzymes. To conclude, the assessed biological activity and the existence of bioactive phytochemicals in the studied plant extract may pave the way for the development of novel pharmaceuticals.

Comparative pharmacokinetic evaluation of glimepiride orodispersable and conventional tablets in rabbits.

OBJECTIVES: Glimepiride Orodispersable Tablets (ODT) were prepared with the goal to have rapid onset of action and higher bioavailability with ease administration to individuals with swallowing difficulty to ameliorate patient compliance. SIGNIFICANCE: Glimepiride is a contemporary hypoglycemic medication that belongs to the family of sulfonylurea derivatives. It is used in type 2 diabetes mellitus. Compliance adherence remains one of the limitations with the conventional drug delivery system especially in pediatric, geriatric, psychiatric, and traveling patients, for such population ODT provides a good alternate dosage form compared with Commercial Tablets. METHOD: The Comparative in vivo pharmacokinetic parameters of the prepared ODT and conventional tablets (CT) were evaluated using an animal model. The plasma concentration of Glimepiride after oral administration of a single dose was determined at predetermined time intervals with HPLC. The pharmacokinetic parameters were calculated using PK Solutions 2.0 from Summit PK® software. RESULTS: The Cmax obtained with ODT (22.08 µg/ml) was significantly (p = 0.006) high, a lower tmax of 3.0 hr was achieved with the orodispersable formulation of the drug. The ODT showed 104.34% relative bioavailability as compared to CT and left shift of tmax as well. CONCLUSION: As per findings of the in vivo investigation, the Glimepiride ODT would be beneficial in terms of patient compliance, quick onset of action, and increased bioavailability.

Synthesis of novel nonsteroidal anti-inflammatory galloyl ß-sitosterol-loaded lignin-capped Ag-based drug.

Biocompatible anti-inflammatory lignin-capped Ag (LCAg) nanoparticles (NPs) were synthesized for the delivery of galloyl ß-sitosterol (Galloyl-BS). ß-Sitosterol (BS) is effective against inflammatory responses, like cancer-induced inflammations. BS was modified via gallic acid esterification to enhance its anti-inflammatory potential. LCAg NPs were synthesized by a green method and loaded with galloyl-BS. For comparison, pure BS was also loaded onto LCAg NPs in a separate assembly. The antioxidant potential of Galloyl-BS was greater (IC50 177 µM) than pure BS. Materials were characterized by FT-IR, SEM, XRD, and Zeta potential. Using UV-Vis spectroscopy, drug release experiments were performed by varying pH, time, concentration, and temperature. Maximum drug release was observed after 18 h at pH 6 and 40 °C. Galloyl-BS showed improved drug loading efficiency, release %age, and antioxidant activity compared to pure BS when loaded onto LCAg NPs. DLCAg exhibited excellent anti-inflammatory activity in rat models. These findings indicate that galloyl-BS (drug)-loaded LCAg (DLCAg) NPs have the potential as an anti-inflammatory agent without any prior release and scavenging in normal cells.

Dose-dependent efficacy of bevacizumab in recurrent glioblastoma.

BACKGROUND: Bevacizumab (BEV), at a standard dose of 10 mg/kg every 2 weeks is associated with prolonged progression-free survival (PFS) but no improvement in overall survival (OS) in recurrent glioblastoma (rGBM). Few studies have examined the potential dose-dependent efficacy of BEV. In Ontario, reimbursement for the costs of BEV varies, and as a result, our practice began to routinely use lower dose regimens. The main aim of this study was to ensure that there was no harm to patients who received the low dose protocol. METHODS: A single-center retrospective study of patients given BEV for rGBM between 2015 and 2020 was performed. Clinical and treatment data including BEV dose regimen [SD (10 mg/kg every 2 weeks) vs. LD (5 mg/kg every 2-3 weeks or 10 mg/kg every 3 weeks)] received at the time of rGBM diagnosis were captured. Overall survival (OS) and progression-free survival (PFS) on BEV were compared using the Kaplan-Meier product-limit method. Log-rank test was used to compare potential predictive factors. Cox regression model was performed for multivariable analysis of OS and PFS. RESULTS: A total of 96 patients were included with a median follow-up duration of 6.84 months (range 1.12-50.63 months) from the date of the first infusion. The LD group consisted of 55 of the 96 patients. By virtue of funding mechanisms for BEV, the median age in the LD group was significantly higher (62 vs. 54 years p = 0.009). There was no difference in MGMT status between the two groups (p = 0.60). The LD group had prolonged median PFS (5.89 months versus 3.22 months; p = 0.0112) and OS (10.23 months versus 6.28 months; p = 0.0010). Multivariable analysis including the dose of BEV, the extent of resection, gender, and age revealed that standard dose of BEV, subtotal resection, and female sex were associated with worse overall survival. Nine patients in the SD group vs. 18 patients in the LD group reported an adverse event related to BEV. CONCLUSION: For patients with recurrent GBM, we found that a low dose regimen of BEV was associated with prolonged OS and PFS compared to the standard dose regimen. Lower dose schedules may be a better and more cost-effective option for patients with rGBM. Lower costs might provide more equitable access to this very important palliative drug.

Preparation of Tamsulosin Hydrochloride-Loaded Mucoadhesive In Situ Gelling Polymeric Formulation for Nasal Delivery in Geriatrics.

This study aimed to prepare tamsulosin hydrochloride (HCl)-loaded in situ gelling formulation by using hydroxypropyl methylcellulose (HPMC), gellan gum, poloxamer 188, and benzalkonium chloride. Physicochemical evaluation of formulations included determination of pH, viscosity, gelation time, gel strength, drug content, and sterility. In silico study was performed to analyze interactions between polymers, drug, and mucin glycoprotein. In vitro degradation time, drug release, ex vivo mucoadhesion time, permeation, in vivo pharmacokinetics, and stability studies were performed to assess the formulation. Formulations were transparent and displayed acceptable physicochemical attributes. Tamsulosin HCl and polymers interacted via non-covalent interactions. HPMC formed hydrogen bonds, hydrophobic and van der Waals interactions with mucin protein while the drug formed hydrogen bonds only. Gel formulation degraded in simulated nasal fluid within 24 h. In situ gelling formulation showed 83.8 ± 1.7% drug release and remained adhered to the mucosa for 24.5 ± 1 h. A higher (~ 1.85 times) drug permeation was recorded through mucosa within 6 h by in situ gelling formulation when compared to control counterparts (aqueous solution of drug and in situ gelling formulation without poloxamer 188). Nasal administration of tamsulosin HCl by using in situ gelling formulation led to a ~ 3.3 and ~ 3.5 times, respectively, higher Cmax (maximum plasma concentration) and AUCtotal (total area under the curve) than the orally administered aqueous solution. Relative bioavailability of drug delivered by nasal in situ gelling formulation was 3.5 times the oral counterpart. These results indicated that the prepared in situ gelling formulation can act as a promising candidate for systemic administration of tamsulosin HCl.

High Dielectric Transparent Film Tailored by Acceptor and Donor Codoping.

High dielectric constant materials are of particular current interests as indispensable components in transistors, capacitors, etc. In this context, there are emerging trends to exploit defect engineering in dielectric ceramics for enhancing the performance. However, demonstrations of similar high dielectric performance in integration-compatible crystalline films are rare. Herein, such a breakthrough via the functionalization of donor-acceptor dipoles by compositional tuning in GaCu codoped ZnO films is reported. The dielectric constant reaches ~200 at 1 kHz and the optical transmittance in visible light reaches ~80%. Importantly, by analyzing the impedance spectroscopy data, prominent relaxation mechanisms in correlation with the dipole properties, enabling consistent explanations of the dielectric constant as a function of frequency are discriminated. The atomistic nature of the dipoles is revealed by the systematic X-ray spectroscopy analysis. Spectacularly, similar trends for the dielectric properties are observed, while synthesizing samples by pulsed laser deposition and ion implantation, indicating the general character of the phenomena.

The first Australian experience with ward-based continuous positive airway pressure for COVID-19 respiratory failure: a retrospective cohort study.

We present the first Australian cohort of patients with COVID-19 respiratory failure managed with escalating respiratory support including continuous positive airway pressure (CPAP) on a standard medical ward at a tertiary Sydney hospital during the 2021 COVID-19 Delta variant outbreak. We demonstrate an equivalent mortality to CPAP delivered in intensive care unit and outline our ward structure and management during the pandemic.

Synthesis and Micromechanistic Studies of Sensitized Bentonite for Methyl Orange and Rhodamine-B Adsorption from Wastewater: Experimental and DFT-Based Analysis.

This work reports the formation of a novel adsorbent, prepared by activating bentonite with cinnamic acid, which is highly efficient to remove dyes from wastewater. The adsorption efficiency of the cinnamic acid activated bentonite was compared with unmodified bentonite by removing methyl orange and rhodamine-B from polluted water. The characterization was performed through X-ray diffraction (XRD) Fourier transform infrared (FTIR) and scanning electron microscopy (SEM). The results indicated that acidic pH and low temperature were more suitable for the selected dyes adsorption. The analysis of the data was done by the Langmuir and Freundlich isotherms; the Freundlich isotherm showed more suitability for the equilibrium data. The data were further analyzed by pseudo-first and pseudo-second-order models to study adsorption kinetics. The results showed that methyl orange and rhodamine-B adsorption obeyed pseudo-order kinetics. The results obtained from this research suggested that acid activation of bentonite with cinnamic acid increased the surface area of the clay and hence enhanced its adsorption efficiency. The maximum adsorption efficiency for the removal of methyl orange and rhodamine-B was up to 99.3 mg g-1 and 44.7 mg g-1, respectively, at 25 °C. This research provides an economical modification technique of bentonite, which makes it cost-effective and a good adsorbent for wastewater treatment.

Functional probiotics of lactic acid bacteria from Hu sheep milk.

BACKGROUND: Probiotics are being considered as valuable microorganisms related to human health. Hu sheep is referred as one of the important sheep breeds in China. Goat milk produced by Hu sheep is characterized with high nutritional value and hypoallergenic in nature. Particularly, this milk contains plenty of milk prebiotic and probiotic bacteria. This study was aimed to scrutinize more bacterial strains from Hu sheep milk with potential probiotic activity. RESULTS: Based on 16S rRNA sequence analysis, pool of forty bacterial strains were identified and evaluated their antimicrobial activities against Staphylococcus aureus, enterohemorrhagic Escherichia coli (EHEC), Salmonella typhimurium, Listeria monocytogenes enterotoxigenic E. coli (ETEC) and Aeromonas caviae. Four out of these isolated strains demonstrated their efficient bacteriostatic ability and potential healthy properties. We also examined the safety aspects of these bacterial candidates including three Lactococcus lactis strains (named as HSM-1, HSM-10, and HSM-18) and one Leuconostoc lactis strain (HSM-14), and were further evaluated via in vitro tests, including antimicrobial activity, cell surface characteristics (hydrophobicity, co-aggregation, and self-aggregation), heat treatment, antibiotic susceptibility, simulated transport tolerance in the gastrointestinal tract, and acid/bile tolerance. The obtained results revealed that HSM-1, HSM-10, HSM-14, and HSM-18 showed high survival rate at different conditions for example low pH, presence of bovine bile and demonstrated high hydrophobicity. Moreover, HSM-14 had an advantage over other strains in terms of gastrointestinal tract tolerance, antimicrobial activities against pathogens, and these results were significantly better than other bacterial candidates. CONCLUSION: Hu sheep milk as a source of exploration of potential lactic acid bacteria (LAB) probiotics open the new horizon of probiotics usage from unconventional milk sources. The selected LAB strains are excellent probiotic candidates which can be used for animal husbandry in the future. Rationale of the study was to utilize Hu sheep milk as a source of potential probiotic LABs. The study has contributed to the establishment of a complete bacterial resource pool by exploring the Hu sheep milk microflora.

Isolating a new Streptomyces amritsarensis N1-32 against fish pathogens and determining its effects on disease resistance of grass carp.

In this study, a Streptomyces strain was isolated from the soil samples of Yanghu Wetland Park in Changsha, Hunan Province. This strain showed excellent antimicrobial activity against 10 fish pathogens, as indicated by the results of the agar-diffusion and oxford cup assays. After 16s rDNA sequencing and physiological & biochemical analyses, it was identified as Streptomyces amritsarensis, namely for S. amritsarensis N1-32. Cytotoxicity test was performed, and the results exhibited that this strain had no toxicity to hepatic L8824 cell line from grass carp liver. The diets supplemented strain N1-32 at concentrations of 1 × 107 cfu/g and 1 × 109 cfu/g was used to feed fish. After 28 days, the expression levels of antioxidant-related genes Nrf2 and Keap1 in the liver and spleen were significantly up-regulated, and the expression of immune-related gene IgM was notably increased in the liver, kidney, head-kidney, and spleen. Toll-like receptor 4 (TLR4) gene expression was up-regulated in the spleen, and TLR4, myeloid differentiation factor 88 (MyD88) gene were up-regulated in the kidney. The survival rate of grass carp was significantly improved after pathogen infection. Whole-genome analysis of N1-32 showed that the strain harbored related genes, capability for producing substances that enhance the immunity of grass carp and inhibit pathogens. A total of 22 gene clusters were identified in the genome, including 5 terpene gene clusters, 4 nonribosomal peptide-synthetase (NRPS) gene clusters and 2 lantipeptide gene clusters. In summary, these results showed that strain N1-32 as a feed additive could regulate grass carp immunity and enhance the resistance of grass carp against fish pathogens.

A Survey for the Ranking of Trajectory Prediction Algorithms on Ubiquitous Wireless Sensors.

The number of wireless sensors in use-for example, the global positioning system (GPS) intelligent sensor-has increased in recent years. These intelligent sensors generate a vast amount of spatiotemporal data, which can assist in finding patterns of movements. These movement patterns can be used to predict the future location of moving objects; for example, the movement of an emergency vehicle can be predicted for health care decision-making. Although there is a body of research work regarding motion trajectory prediction, there are no guidelines for choosing algorithms best suited for individual needs in uncertain and complex situations and as per the application domains. In this paper, we surveyed existing trajectory prediction algorithms. These algorithms are further ranked scientifically in terms of accuracy (performance), ease of use, and best fit as per the available datasets. Our results show three top algorithms, namely NextPlace, the Markov model, and the hidden Markov model. This study can be beneficial for multicriteria decision-making for various disciplines, including health care.

BSA Binding, molecular docking and in vitro biological screening of some new 1, 2, 4-triazole heterocycles bearing azinane nucleus.

A series of new compounds (5a-q), derived from 5-(1-(4-nitrophenylsulfonyl) piperidin-4-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol (3) were proficiently synthesized to evaluate their biological activities. 1-(4-Nitrophenylsulfonyl) piperidine-4-carbohydrazide (2) was refluxed with phenylisothiocyanate to yield an adduct which was cyclized to compound 3 by reflux reaction with 10 % potassium hydroxide. The targeted compounds 5a-q, were synthesized by stirring alkyl/aralkyl halides (4a-q) and compound 3 in a polar aprotic solvent. 1H-NMR, 13C-NMR, EI-MS and IR spectral techniques were employed to confirm the structures of all the synthesized compounds. The compounds were biologically evaluated for BSA binding studies followed by anti-bacterial, anti-inflammatory and acetylcholinesterase (AChE) activities. The active sites responsible for the best AChE inhibition were identified through molecular docking studies. Compound 5e bearing 4-chlorobenzyl moiety found most active antibacterial and anti-inflammatory agent among the synthesized compounds. The whole library of synthesized compounds except compounds 5d and 5f was found highly active for AChE inhibition and recommended for in vivo studies so that their therapeutic applications may come in utilization.

Taxifolin prevents postprandial hyperglycemia by regulating the activity of α-amylase: Evidence from an in vivo and in silico studies.

There has been a dramatic increase in the prevalence of diabetes mellitus (DM) and its associated complications globally. The postprandial stage of DM involves prompt elevation in the levels of blood glucose and α-amylase, a carbohydrate-metabolizing enzyme is mainly involved in the regulation of postprandial hyperglycemia. This study was designed to assess the ability of a well-known flavonoid, taxifolin (TFN), against postprandial hyperglycemia and its inhibitory effects on α-amylase activity through the assessment of therapeutic potentials of TFN in an alloxan-induced diabetic animal model. The binding potential TFN with an α-amylase receptor was also investigated through molecular dynamics (MD) simulation and docking of to compare the binding affinities and energies of TFN and standard drug acarbose (ACB) with target enzyme. TFN significantly improved the postprandial hyperglycemia, lipid profile, and serum levels of α-amylase, lipase, and C-reactive protein in a dose-dependent manner when compared with that of either DM-induced and ACB-treated alloxan-induced diabetic rats. Moreover, TFN also enhanced the anti-oxidant status and normal functioning of the liver in alloxan-induced diabetic rats more efficiently as compared to that of ACB-treated alloxan-induced diabetic rats. Therapeutic potentials of TFN were also verified by MD simulation and docking results, which exhibited that the binding energy and affinity of TFN to bind with receptor was significantly higher as compared to that of ACB. Hence, the results of this study signify that TFN might be a potent inhibitor of α-amylase that has the potential to regulate the postprandial hyperglycemia along with its anti-inflammatory and anti-oxidant properties during the treatment of DM.

Impact of Pruritus on Sleep Quality of Hemodialysis Patients: A Systematic Review and Meta-Analysis.

: Chronic kidney disease (CKD)-associated pruritus is a common and disturbing condition which has a negative impact on sleep quality, as well as overall health-related quality of life of patients receiving hemodialysis. To date, no systematic review has been undertaken, and there is a lack of concise evidence that statistically quantifies the impact of pruritus based on published data. A systematic search was done for original articles published in peer-reviewed English journals from database inception on 20 December, 2018, in the following databases: PubMed, MEDLINE, EMBASE, Ovid, CINHAL, ProQuest, and Scopus. A total of 9217 research articles were identified. After removal of duplicates and screening for titles and abstracts, 28 articles were selected. The prevalence of disturbed sleep was 4-94%, while the pooled proportion on random effect in the study was 40% (95% CI = 0.30 to 0.49); I2 = 99.8%. However, the prevalence of disturbed sleep quality and quantity due to pruritus was 9-76%, and the pooled proportion on random effect in the study was 50% (95% CI = 0.37 to 0.64); I2 = 99.8%. Patients undergoing hemodialysis who are affected by CKD-associated pruritus have a higher chance of experiencing sleep disturbances. The prevalence of disturbed sleep due to CKD-associated pruritus was found to be 9-76% in the included studies for patients receiving hemodialysis therapy.

Influence of levodropropizine and hydroxypropyl-ß-cyclodextrin association on the physicochemical characteristics of levodropropizine loaded in hydroxypropyl-ß-cyclodextrin microcontainers: Formulation and in vitro characterization.

BACKGROUND: Poorly water-soluble drugs do not dissolve well in aqueous-based gastrointestinal fluid; therefore, they are not well absorbed. Thus, employing a suitable solubility enhancing technique is necessary for such a drug. Drug/HP­ß­CD complexation is a promising way to improve solubility and dissolution of a poorly water-soluble drug. Levodropropizine was used as a model drug in this study. OBJECTIVES: The purpose of this research was to enhance the aqueous solubility and dissolution rate of levodropropizine by employing the inclusion complexation technique. MATERIAL AND METHODS: A microparticle formulation was prepared from levodropropizine and hydroxypropyl-ß-cyclodextrin (HP­ß­CD) in a 1:1 molar ratio through the spray-drying technique. The host-guest relationship between levodropropizine and HP­ß­CD was also investigated using the molecular docking computational methodology. The aqueous solubility and dissolution rate of levodropropizine in formulations were assessed and compared with those of the drug alone. X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR) were applied for the solid-state characterization of the prepared samples. RESULTS: According to the research outcomes, the levodropropizine/HP­ß­CD formulation had enhanced the aqueous solubility (351.12 ±13.26 vs 92.76 ±5.00 mg/mL) and dissolution rate (97.83 ±3.36 vs 3.12 ±1.76% in 10 min) of levodropropizine, compared to the plain drug powder. The levodropropizine/ HP­ß­CD formulation had converted the crystalline drug into its amorphous counterpart. Furthermore, no covalent interaction was found to exist between levodropropizine and HP­ß­CD. The spray-dried particles were discrete. Each particle had a shriveled appearance. CONCLUSIONS: The levodropropizine/HP­ß­CD formulation is, therefore, recommended for the more effective administration of levodropropizine through the oral route.

A case of non-lacrimal immunoglobulin G4 (IgG4)-related orbital disease with mastitis.

IgG4-related orbital disease is a recognised cause for orbital inflammation. As its awareness increases and diagnostic accuracy improves there will be an increased number of cases being identified. This unique case demonstrates for the first time, with histological evidence, a case of a non-lacrimal IgG4-related orbital disease with concurrent IgG4-related mastitis. We describe a 47 year old who presented with a supraorbital swelling and mass. This was initially successfully treated with oral steroids and was later excised on recurrence. Immunohistochemical and blood serum analysis confirmed IgG4-related orbital disease. On systemic enquiry she was found to have a mass of the breast, which was shown to be IgG4-related mastitis. She is currently asymptomatic with no sign of recurrence and is under long-term surveillance. This case highlights the importance of systemic work up in patients presenting with orbital foci of IgG4 disease.

Phylogenetics, ancestral state reconstruction, and a new infrafamilial classification of the pantropical Ochnaceae (Medusagynaceae, Ochnaceae s.str., Quiinaceae) based on five DNA regions.

Ochnaceae s.str. (Malpighiales) are a pantropical family of about 500 species and 27 genera of almost exclusively woody plants. Infrafamilial classification and relationships have been controversial partially due to the lack of a robust phylogenetic framework. Including all genera except Indosinia and Perissocarpa and DNA sequence data for five DNA regions (ITS, matK, ndhF, rbcL, trnL-F), we provide for the first time a nearly complete molecular phylogenetic analysis of Ochnaceae s.l. resolving most of the phylogenetic backbone of the family. Based on this, we present a new classification of Ochnaceae s.l., with Medusagynoideae and Quiinoideae included as subfamilies and the former subfamilies Ochnoideae and Sauvagesioideae recognized at the rank of tribe. Our data support a monophyletic Ochneae, but Sauvagesieae in the traditional circumscription is paraphyletic because Testulea emerges as sister to the rest of Ochnoideae, and the next clade shows Luxemburgia+Philacra as sister group to the remaining Ochnoideae. To avoid paraphyly, we classify Luxemburgieae and Testuleeae as new tribes. The African genus Lophira, which has switched between subfamilies (here tribes) in past classifications, emerges as sister to all other Ochneae. Thus, endosperm-free seeds and ovules with partly to completely united integuments (resulting in an apparently single integument) are characters that unite all members of that tribe. The relationships within its largest clade, Ochnineae (former Ochneae), are poorly resolved, but former Ochninae (Brackenridgea, Ochna) are polyphyletic. Within Sauvagesieae, the genus Sauvagesia in its broad circumscription is polyphyletic as Sauvagesia serrata is sister to a clade of Adenarake, Sauvagesia spp., and three other genera. Within Quiinoideae, in contrast to former phylogenetic hypotheses, Lacunaria and Touroulia form a clade that is sister to Quiina. Bayesian ancestral state reconstructions showed that zygomorphic flowers with adaptations to buzz-pollination (poricidal anthers), a syncarpous gynoecium (a near-apocarpous gynoecium evolved independently in Quiinoideae and Ochninae), numerous ovules, septicidal capsules, and winged seeds with endosperm are the ancestral condition in Ochnoideae. Although in some lineages poricidal anthers were lost secondarily, the evolution of poricidal superstructures secured the maintenance of buzz-pollination in some of these genera, indicating a strong selective pressure on keeping that specialized pollination system.