Mutational spectrum associated with oculocutaneous albinism and Hermansky-Pudlak syndrome in nine Pakistani families.

BACKGROUND: Oculocutaneous albinism (OCA) is a genetically heterogeneous condition that is associated with reduced or absent melanin pigment in the skin, hair, and eyes, resulting in reduced vision, high sensitivity to light, and rapid and uncontrolled eye movements. To date, seventeen genes have been associated with OCA including syndromic and non-syndromic forms of the condition. METHODS: Whole exome sequencing (WES) was performed to identify pathogenic variants in nine Pakistani families with OCA, with validation and segregation of candidate variants performed using Sanger sequencing. Furthermore, the pathogenicity of the identified variants was assessed using various in-silico tools and 3D protein structural analysis software. RESULTS: WES identified biallelic variants in three genes explaining the OCA in these families, including four variants in TYR, three in OCA2, and two in HPS1, including two novel variants c.667C > T: p.(Gln223*) in TYR, and c.2009 T > C: p.(Leu670Pro) in HPS1. CONCLUSIONS: Overall, this study adds further knowledge of the genetic basis of OCA in Pakistani communities and facilitates improved management and counselling services for families suffering from severe genetic diseases in Pakistan.

Design, synthesis and evaluation of novel norfloxacin analogs as potent anticancer and antioxidant agents.

Aim: To synthesize a novel series of norfloxacin analogs and to evaluate biological activity. Methodology: Novel norfloxacin analogs were synthesized and characterized by NMR and mass spectrometry. Antiproliferative and antioxidant properties were studied. Results: Compound 2f was the most potent against HeLa cell-line with 100% inhibition of cell viability IC50 = 3.1 ± 0.2 µM. All compounds exhibit moderate to excellent antioxidant properties. Docking study demonstrates higher binding affinity of compounds with respective anticancer (B-cell lymphoma-2) and (tyrosinase) antioxidant targets. In silico absorption, distribution, metabolism and excretion profile of compounds proves all synthesized compounds follow Lipinski's rule of drug likeness, non toxic and possess passive gastrointestinal absorption. Conclusion: The biological profile suggest that the synthesized norfloxacin analogs can be a novel scaffold for future anticancer drug development.

[Box: see text].

Formulation and characterization of glipizide solid dosage form with enhanced solubility.

Glipizide, a poor water-soluble drug belongs to BCS class II. The proposed work aimed to enhance the solubility of glipizide by preparing solid dispersions, using polyvinyl pyrrolidone (PVP) and polyethylene glycol (PEG). Solvent evaporation method was used for the preparation of glipizide solid dispersions. Solid dispersions were prepared in four different drug-to-polymer ratios i.e. 1:1, 1:2, 1:3 and 1:4. Mainly effect of three polymers (PVP K30, PVP K90 and PEG 6000) was evaluated on the solubility and dissolution of glipizide. The in-vitro dissolution of all prepared formulations was performed under pH 6.8 at 37°C using USP type II apparatus. In-vitro dissolution results revealed that the formulations having high concentrations of the polymer showed enhanced solubility. Enhancements in the solubility and rate of dissolution of the drug were noted in solid dispersion formulations compared to the physical blends and pure drug. Solid dispersions containing polyvinyl pyrrolidone exhibited a more favorable pattern of drug release compared to the corresponding solid dispersions with PEG. An increase in the maximum solubility of the drug within the solid dispersion systems was observed in all instances. Two solid dispersion formulations were optimized and formulated into immediate-release tablets, which passed all the pharmacopoeial and non-pharmacopoeial tests. Fourier transformed Infrared (FTIR) spectroscopy X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) were used to indicate drug: polymer interactions in solid state. Analysis of the solid dispersion samples through characterization tests indicated the compatibility between the drug and the polymer.

Development, characterization and In-vitro evaluation of guar gum based new polymeric matrices for controlled delivery using metformin HCl as model drug.

Currently, hydrogels are considered as ideal biomaterials due to their unique structure and characteristics that facilitates considerable hydrophilicity, swelling, drug loading and release. In this study, we report pH-responsive GG-MAA-AMPS hydrogel delivery system prepared via free radical polymerization technique. Hydrogels were loaded with Metformin HCl as a model drug. Hydrogels were characterized through Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and scanning electron microscopy (SEM). FTIR confirmed the successful crosslinking of reactants, hydrogel network formation and drug loading. TGA and DSC proved the higher thermal stability of reactants after crosslinking and drug loading. XRD analysis showed decrease in crystallinity of drug after loading into the hydrogels. SEM revealed smooth and glassy appearance of both loaded and unloaded hydrogels. Gel content was increased with increase in concentration of reactants. Drug entrapment was decreased by increasing concentration of GG and AMPS while MAA acted inversely. Hydrogels displayed pH-dependent swelling and drug release behavior being high at pH 6.8 and 7.4 while low at acidic pH (1.2). Oral tolerability in rabbits showed that hydrogels were safe without causing any hematological or histopathological changes in healthy rabbits. Based on the obtained results, GG-MAA-AMPS can be considered as potential carrier for metformin HCl as well as other hydrophilic drugs.

Chitosan/guar gum-based thermoreversible hydrogels loaded with pullulan nanoparticles for enhanced nose-to-brain drug delivery.

The biopolymers-based two-fold system could provide a sustained release platform for drug delivery to the brain resisting the mucociliary clearance, enzymatic degradation, bypassing the first-pass hepatic metabolism, and BBB thus providing superior bioavailability through intranasal administration. In this study, poloxamers PF-127/PF-68 grafted chitosan HCl-co-guar gum-based thermoresponsive hydrogel loaded with eletriptan hydrobromide laden pullulan nanoparticles was synthesized and subjected to dynamic light scattering, Fourier transform infrared spectroscopy, thermal analysis, x-ray diffraction, scanning electron microscopy, stability studies, mucoadhesive strength and time, gel strength, cloud point assessment, rheological assessment, ex-vivo permeation, cell viability assay, histology studies, and in-vivo Pharmacokinetics studies, etc. It is quite evident that CSG-EH-NPs T-Hgel has an enhanced sustained release drug profile where approximately 86 % and 84 % of drug released in phosphate buffer saline and simulated nasal fluid respectively throughout 48 h compared to EH-NPs where 99.44 % and 97.53 % of the drug was released in PBS and SNF for 8 h. In-vivo PKa parameters i.e., mean residence time (MRT) of 11.9 ± 0.83 compared to EH-NPs MRT of 10.2 ± 0.92 and area under the curve (AUCtot) of 42,540.5 ± 5314.14 comparing to AUCtot of EH-NPs 38,026 ± 6343.1 also establish the superiority of CSG-EH-NPs T-Hgel.

Exploring the factors and barriers of healthcare professionals in tertiary care hospitals toward pharmacovigilance: a multicenter study from Khyber Pakhtunkhwa, Pakistan.

BACKGROUND: Spontaneous Adverse drug reactions (ADRs) reporting is a cornerstone for a successful pharmacovigilance program as under-reporting of ADRs remains a major issue around the globe. The current study aimed to assess the knowledge attitude and practices of health care professionals regarding pharmacovigilance along with barriers and factors to encourage ADR reporting at tertiary care hospitals of Khyber-Pakhtunkhwa, Pakistan. METHODS: A questionnaire-based cross-sectional survey was conducted, using the convenience sampling method to collect the data from doctors, nurses, and pharmacists working in seven tertiary care hospitals from seven districts of Khyber-Pakhtunkhwa province, Pakistan, between July 2019 and March 2020. RESULTS: During the study, a total of 830 questionnaires were distributed, out of which 669 were returned (response rate 80.6%). Overall, Healthcare professionals exhibited poor knowledge (79.5%) about ADR reporting and pharmacovigilance however, 73.5% of pharmacists were more knowledgeable as compared to 18.7% doctors and 13.8% nurses (p < .001). Moreover, poor reporting practices were displayed by 95.6% doctors, 94.4% nurses, 94.4 and 75.5% pharmacists (p < .001). However, the majority of healthcare professionals showed an overall positive attitude (94%) toward ADR reporting. The most frequently cited barriers were unavailability of reporting forms (92.5%), absence of a professional environment to discuss ADRs (82.5%), and lack of training (81.8%) whereas, most common factors to encourage ADR reporting were obligatory reporting (85.9%) and provision of ADR management guidelines and training (84.3%). A significant relation was found between the healthcare professionals and their professional status with the overall knowledge, attitude, and practice (KAP) scores (p < .001) whereas a medium, positive correlation was found between the knowledge and practice of pharmacovigilance and ADR reporting by the healthcare professionals (r = 0.321, n = 669, p < .001). CONCLUSION: There is an overall lack of knowledge and poor reporting practices among health care professionals on ADR reporting and pharmacovigilance. Hence the study suggests that strategies should be devised by all the stakeholders to properly educate and train the healthcare professionals in this area to enhance overall patient safety and safe use of medicines.

An Exploration of Knowledge, Attitude, and Practices of Physicians toward Pharmacovigilance at Tertiary Care Hospitals in Khyber-Pakhtunkhwa Province, Pakistan.

Drug safety assures the effectiveness, safety, and security of drugs, vaccines, and other biologicals to protect public health. Medication-related errors coupled with unjudicial medication practices often cause a catastrophic impact on the healthcare system globally. The present study aimed to assess the knowledge, attitude, and practice of physicians toward pharmacovigilance and barriers to adverse drug reaction (ADR) reporting at tertiary care hospitals in Khyber-Pakhtunkhwa (KP) province, Pakistan. A descriptive cross-sectional study was conducted among registered doctors working in seven tertiary care hospitals from seven administrative divisions of KP province of Pakistan from July 2019 to March 2020. During the study period, 358 physicians who fulfilled the inclusion criteria and agreed to participate completed and returned the validated structured questionnaires. Descriptive and inferential statistics were applied for data analysis. The majority of physicians had poor knowledge (81.3%) regarding pharmacovigilance along with poor reporting practices (94.9%), although (96.5%) had a positive attitude toward ADR reporting. A significant barrier identified was the unavailability of reporting forms (95.9%), whereas mandatory ADR reporting (96.2%) was the major factor to encourage ADR reporting. Physicians aged ≥ 41 and experience ≥ 11 years had significantly more knowledge than other categories (P < 0.001). Significant association (P < 0.001) of physicians' knowledge and practice were found where 77.2% of the participants having poor knowledge reported poor practices. Physicians' understanding of pharmacovigilance was suboptimal, although they have a positive attitude toward ADR reporting. Thus, there is a need for continuous education and training programs to support pharmacovigilance activities that could improve physicians' understanding.

Improved drug delivery and accelerated diabetic wound healing by chondroitin sulfate grafted alginate-based thermoreversible hydrogels.

Injectable hydrogels with multifunctional tunable properties comprising biocompatibility, anti-oxidative, anti-bacterial, and/or anti-infection are highly preferred to efficiently promote diabetic wound repair and its development remains a challenge. In this study, we report chondroitin sulphate (CS) and sodium alginate (SA)-based injectable hydrogel using solvent casting method loaded with curcumin that could potentiate reepithelization, increase angiogenesis, and collagen deposition at wound microenvironment to endorse healing cascade. The physical interaction and self-assembly of chondroitin sulfate grafted alginate (CS-Alg-g-PF127) hydrogel were confirmed using nuclear magnetic resonance (1H NMR) and Fourier transformed infrared spectroscopy (FT-IR), and cytocompatibility was confirmed by fibroblast viability assay. The Masson's trichrome (MT) and hematoxylin and eosin (H&E) results revealed that blank chondroitin sulfate grafted alginate (CS-Alg-g-PF127) and CUR loaded CS-Alg-g-PF127 hydrogel had promising tissue regenerative ability, and showing enhanced wound healing compared to other treatment groups. The controlled release of CUR from injectable hydrogel was evaluated by drug release studies and pharmacokinetic profile (PK) using high-performance liquid chromatography (HPLC) that exhibited the mean residence time (MRT) and area under the curve (AUC) was increased up to 16.18 h and 203.64 ± 30.1 µg/mL*h, respectively. Cytotoxicity analysis of the injectable hydrogels using 3 T3-L1 fibroblasts cells and in vivo toxicity evaluated by subcutaneous injection for 24 h followed by histological examination, confirmed good biocompatibility of CUR loaded CS-Alg-g-PF127 hydrogel. Interestingly, the results of in vivo wound healing by injectable hydrogel showed the upregulation of fibroblasts-like cells, collagen deposition, and differentiated keratinocytes stimulating dermo-epidermal junction, which might endorse that they are potential candidates for excisional wound healing models.

Synthesis, Characterization and Safety Evaluation of Sericin-Based Hydrogels for Controlled Delivery of Acyclovir.

Conventional formulations of antiviral drug acyclovir have various limitations such as low bioavailability. The current study was aimed at developing polymeric matrices for the controlled delivery of acyclovir using sericin as polymer and acrylic acid (AA) as a monomer. The free radical polymerization technique was used for hydrogel formulation. Briefly, sericin was chemically cross-linked with acrylic acid. N'-N'-methylene bis-acrylamide (MBA) and ammonium persulfate (APS) were used as cross-linker and initiator, respectively. FTIR spectra showed that acyclovir was successfully loaded into sericin hydrogel. SEM micrographs revealed that the outer surface was solid-like and smooth. According to DSC thermograms, the developed polymeric network was thermally stable. Amorphous nature of acyclovir was observed in XRD. The pH of medium and reactants' concentration affected swelling dynamics and acyclovir release pattern. In addition, drug release occurred through a diffusion-controlled process. Sericin hydrogel suspension was well tolerable up to 3800 mg/kg of rabbits' body weight. Haematology and serum chemistry results were well within the range signifying normal liver and kidney functions. Similarly, histopathology slides of the rabbit's vital organs were also in normal condition without causing any histopathological change. It was concluded from the findings that sericin-co-AA polymeric matrices are ideal for the pH-dependent delivery of acyclovir.

Pharmacokinetic Profile of Oxaliplatin-Loaded pH-Responsive Hydrogels in Rabbits.

BACKGROUND: Oxaliplatin (OXP), a 3rd generation platinum compound, which causes severe side effects due to; impulse high concentration in the bloodstream thereby exposing healthy cells at a high ratio, nonspecific delivery at the target site and non-compliance is administered intravenously. OBJECTIVE: The project was aimed at the development, characterization, and in-vitro and in-vivo evaluation of pHresponsive hydrogels for oral administration of OXP. METHODS: Hydrogel formulations were synthesized through a free radical polymerization technique followed by brief characterization using various techniques. The hydrogels were investigated for various in-vitro studies such as sol-gel, drug loading, swelling, drug release, and MTT-assay. While in-vivo studies such as oral tolerability, histopathology, and hematology studies were performed on rabbits. A simple and sensitive HPLC-UV method was optimized and the comparative pharmacokinetic study was performed in rabbits using OXP-oral solution and OXP-loaded hydrogels. RESULTS: In-vitro characterization confirmed that the reactant was successfully crosslinked to form thermally stable hydrogels with decreased crystallinity and rough surface. Swelling and drug release showed that hydrogels were more responsive to basic pH (6.8 and 7.4) in comparison with pH 1.2. The blank hydrogels were cytocompatible as more than 95% of the cells were viable while free OXP and OXP-loaded hydrogels displayed dosedependent cytotoxic effect. In-vivo studies confirmed that chitosan and gelatin hydrogel suspension was well tolerable up to 3800 mg/kg and 4000 mg/kg of body weight, respectively. Hematology and serum chemistry reports were well within the range suggesting normal liver and kidney functions. Similarly, histopathology slides of rabbit vital organs were also found normal without causing any histopathological change. CONCLUSION: HPLC-UV method was successfully optimized for OXP detection in oral solution and hydrogels administered to rabbits. A significant difference was found among various pharmacokinetic parameters by comparing the two groups including half-life (t1/2), tmax, Cmax, AUCtot MRT, Vz, and Lz.

Pharmacological exploration of traditional plants for the treatment of neurodegenerative disorders.

Alzheimer's disease (AD) is clinically characterized as memory deficits, altered behavior and impaired cognitive functions. The most important risk factor for AD is aging and mounting. Evidences suggested in different studies that traditionally used plants in Asia, China, and Europe significantly affect aging and AD involved neurodegeneration pathways. Research into ethnobotanicals for impaired memory and cognition has been burgeoned in last decades. The inclusion and exclusion criteria for the plant selection were based on reputed herbs recommended for treatment of neurological disorders and their scientific validation to cure neurodegenerative disorders. A range of traditional plants imparts effects via acetylcholinesterase activity, ß-amyloid peptide formation in plaques, neurotrophic factors and through antioxidant activity. On one side preclinical investigations identified promising drug candidates for AD, on the other side, clinical evidences are still pending. Presently, according to WHO, around more than 80% world population relay on natural remedies to cure their health related issues. Plants contain rich source of primary and secondary metabolites for improving health problems. Pharmaceutical industry is facing intriguing challenges like elevated cost and unendurable risk management due to the high burden of neurodegenerative disorders. A significant shift of drug discovery is being witnessed from synthetic moieties to herbal formulation.

Effect of varying quantities of polymer on preparation and stability evaluation of carbamazepine cocrystals with dicarboxylic acid coformers.

The current study is an attempt to explore the effect of varying quantities of hydroxypropyl cellulose (HPC) polymer on carbamazepine (CBZ) cocrystal formation with dicarboxylic acid coformers i.e., malonic acid (MA), succinic acid (SA), glutaric acid (GA), and adipic acid (AA). The cocrystals were first prepared without polymer by slurry crystallization method and then tried with different quantities of the polymer. The prepared samples were characterized by Powder X-ray Diffraction (XRPD). The characterization results indicate that in methanol pure carbamazepine-malonic (CBZ-MA) and carbamazepine-adipic acid (CBZ-AA) cocrystal can be prepared, while in ethanol and acetone pure carbamazepine-succinic (CBZ-SA) and carbamazepine-glutaric acid (CBZ-GA) cocrystals can be obtained respectively. The same cocrystals were tried using HPC polymer in three different quantities. The characterization results showed that a higher quantity of HPC polymer transforms CBZ-MA cocrystal polymorph-I to polymorph-II. The CBZ-SA and CBZ-GA cocrystal formation somehow inhibited as the concentration of HPC polymer increases. But on the other side, the formation of CBZ-AA cocrystal utterly not inhibited in the presence of varying quantities of HPC polymer. Furthermore, 11 different quantities of HPC were tried to know about the inhibitory concentration of HPC on CBZ-AA cocrystal formation. The CBZ-AA cocrystal preparation was not inhibited even at higher quantities of HPC compared to the coformer. Additionally, the effect of three different quantities of HPC on the thermal stability of the CBZ-AA cocrystal was investigated. Moreover, the stability of pure CBZ at 92% relative humidity (RH) condition was compared to CBZ-AA cocrystal with and without HPC polymer. The CBZ-AA cocrystal with and without HPC polymer was more stable than pure CBZ.

Phytochemical profiling and evaluation of modified resazurin microtiter plate assay of the roots of Trillium govanianum.

Trillium govanianum Wall. ex D. Don (Melanthiaceae alt. Trilliaceae), is native to the Himalayas. The present study, for the first time, was undertaken to explore the antimicrobial potential, to determine the minimum inhibitory concentration (MIC) values of the methanol extract of the roots of Trillium govanianum and its solid phase extraction (SPE) fractions by using resazurin microtiter assay (REMA) against Gram positive and Gram negative bacterial registered strains and to carry out phytochemical analysis. The remarkable amount of gallic acid equivalent phenolic and quercetin equivalent flavonoid content was manifested by MeOH extract (20.27 ± 3.03 mg GAE/g DW and 9.25 ± 0.50 mg QE/g DW respectively). The GC/MS analysis revealed the presence saturated and unsaturated components. Considerable level of antibacterial potential against Gram-positive bacteria (MIC: 2.5-0.009 mg/mL) than against Gram-negative bacteria (MIC: 2.5-0.165 mg/mL) were observed. The use of microtiter plates has the advantage of lower cost, fast and quantitative results.

Synthesis, Characterization and Safety Profiling of Eudragit-Based pHResponsive Hydrogels: A Promising Platform for Colonic Delivery of Losartan Potassium.

OBJECTIVE: The aim of the present study was to design an efficient delivery system with an anticipated swelling and drug release properties for a prolonged drug release as well as to target colon for various hydrophilic drugs. METHOD: For this purpose, the pH-responsive hydrogel comprising a combination of Eudragit and acrylic acid was formed. The hydrogels were characterized for spectral (FTIR), thermal (TGA/DSC), structural (XRD), and morphological (SEM) investigations. Oral tolerability was assessed in rabbits for biocompatibility and oral use of the prepared hydrogels. RESULTS: The results showed that an increased incorporation of Eudragit and cross-linking agent retorted the swelling, drug loading, and drug release properties at both acid (pH 1.2) and basic pH (pH 6.8 and 7.4) , while acrylic acid presented the inverse results. The oral tolerability and toxicity studies depicted that the developed hydrogels were safe up to 3800 mg/kg body weight and caused no hematological or histopathological changes when compared with the control group. CONCLUSION: Therefore, the newly developed formulations presented adequate swelling, drug loading, release behavior, and biocompatibility properties and thus can be used as a promising tool for the colonic delivery of various hydrophilic drugs.

Antioxidant, Antimicrobial, Cytotoxic, and Protein Kinase Inhibition Potential in Aloe vera L.

Aloe vera is a multifunctional plant that has gained acceptance as an excellent home remedy source in Asia and the world. The present study was intended to evaluate the phytochemical contents and in vitro antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities in different fractions of A. vera leaf. Methanolic extract of A. vera leaves was fractionated using column chromatography and ten fractions (AV1-AV10) were obtained. Phenolics composition, antioxidant, antimicrobial, antileishmanial, and protein kinase inhibition activities were evaluated using standard protocols. Well-known compounds of A. vera were used for in silico study against enzymes involved in brine shrimp and antileishmanial and hyphae formation inhibition assay on the basis of results. Five fractions (AV3 to AV7) possess potential total phenolics and flavonoids contents along with significant biological activities. AV4 fraction exhibited the highest total phenolics content 332.4 ± 32.6µg GAE/mg and total antioxidant activity 150.4 ± 25.815µg AAE/mg determined by phosphomolybdenum complex assay. Fraction AV6 showed 95% antileishmanial effect as well as the lowest LD50 value of 0.5305µg/mL in brine shrimp lethality assay. The Protein Kinase inhibition potential in A. vera leaves was determined for the first time and three fractions AV1, AV6, and AV7 depicted activity with the highest zone of inhibition up to 21±0.5mm (AV7). Docking analysis showed that A. vera contains anthraquinones, anthrones, chromones, and polysaccharides responsible for synergistic cytotoxic, antileishmanial, antibacterial, and antioxidant potential of this plant. Therefore, with more studies, A. vera could probably have the potential to be used for drug development against leishmaniasis.

Pectin-based (LA-co-MAA) semi-IPNS as a potential biomaterial for colonic delivery of oxaliplatin.

This study describes the fabrication of chemically crosslinked pectin-based LA-co-MAA hydrogels through free radical polymerization technique for the colonic delivery of oxaliplatin. Methylene bisacrylamide was used as a crosslinking agent and ammonium persulfate as an initiator. The successful fabrication and drug loading were confirmed through Fourier transform infrared spectroscopy (FTIR). The thermal investigations through differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) suggested the higher thermal stability of the unloaded and OXP-loaded formulations as compared to the raw materials. X-ray diffraction (XRD) analysis showed a decrease in crystallinity after crosslinking. The swelling, drug loading, and drug release were increased with an increase in the concentration of pectin and lactic acid (LA) while methacrylic acid (MAA) displayed an inverse behavior. The in-vitro biodegradability was evaluated against lysozyme and collagenase. The results showed that the hydrogels were stable against blank PBS as compared to lysozyme and collagenase. MTT-assay proved that the blank hydrogels were cytocompatible while free OXP and OXP-loaded hydrogels displayed dose-dependent effect against Vero, MCF-7, and HCT-116 cell lines. The oral tolerability study in rabbits confirmed that the hydrogel dispersion was well-tolerable up to 3650 mg/kg of body weight without causing any histopathological or hematological changes when compared with the control group.

Effect of commercial and green synthesized ZnO NPs in murine model of chloroquine-induced pruritus.

Purpose: To investigate the effects of zinc oxide nanoparticles (ZnO NPs) on chloroquine (CQ)-induced itching, and overall behavior of mice after oral administration of ZnO NPs of various sizes and doses. Background: With the wide-spread use of ZnO NPs in pharmaceuticals and cosmetics, concerns about their safety and toxicity are also increasing. Multiple aspects of ZnO NPs regarding cytotoxicity and tolerability are under investigation globally. Still, a clear conclusion about their safety has not been reached. Chloroquine phosphate is an antimalarial with known side effects of itching in humans and animals. In this study, CQ was used to induce itching in mice, and the effects of ZnO NPs on scratching and other neurological behavior of mice were observed. Methods: Female BALB/c mice were divided into eleven groups of six mice each. ZnO NPs of various sizes and doses were administered orally 1 hour before CQ (32 mg/kg body weight) was administered subcutaneously. The effect of ZnO NPs on CQ-induced pruritus was observed for the next 30 minutes. Simultaneously, overall behavioral changes (socialization and locomotion) were also recorded using a video camera. Results: A significant reduction (P˂0.001) in scratching bouts was observed at all three doses of ZnO NPs (particle sizes 100, 30 nm, and green synthesized 30 nm). Locomotion was reduced significantly (P˂0.001) in ZnO NPs-treated groups in comparison to normal saline and CQ group, additionally, a significant increase in socialization (P˂0.05) was observed in ZnO NP-treated groups as compared to CQ group. Conclusion: ZnO NPs, instead of aggravating the dermatological condition, ameliorated the pruritus. All sizes of ZnO NPs used significantly improved socialization among mice and reduced locomotion activity.

Facile Synthesis of Chitosan Based-(AMPS-co-AA) Semi-IPNs as a Potential Drug Carrier: Enzymatic Degradation, Cytotoxicity, and Preliminary Safety Evaluation.

OBJECTIVE: The study describes the development of chitosan-based (AMPS-co-AA) semi-IPN hydrogels using free radical polymerization technique. METHODS: The resulting hydrogels were characterized using Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), X-Ray diffraction (XRD), and Scanning Electron Microscopy (SEM). The successful crosslinking of chitosan, 2- Acrylamido-2-Methylpropane Sulfonic Acid (AMPS), and Acrylic Acid (AA) was confirmed by FT IR. Unloaded and drug-loaded hydrogels exhibited higher thermal stability after crosslinking compared to the individual components. XRD confirmed the decrease in crystallinity after hydrogel formation and molecular dispersion of Oxaliplatin (OXP) in the polymeric network. SEM showed rough, vague and nebulous surface resulting from crosslinking and loading of OXP. RESULTS: The experimental results revealed that swelling and drug release were influenced by the pH of the medium being low at acidic pH and higher at basic pH. Increasing the concentration of chitosan and AA enhanced the swelling, drug loading and drug release while AMPS was found to act inversely. CONCLUSION: It was confirmed that the hydrogels were degraded more by specific enzyme lysozyme as compared to the non-specific enzyme collagenase. In-vitro cytotoxicity suggested that the unloaded hydrogels were non-cytotoxic while crude drug and drug-loaded hydrogel exhibited dose-dependent cytotoxicity against HCT-116 and MCF-7. Results of acute oral toxicity on rabbits demonstrated that the hydrogels are non-toxic up to 3900 mg/kg after oral administration, as no toxicity or histopathological changes were observed in comparison to control rabbits. These pH-sensitive hydrogels appear to provide an ideal basis as a safe carrier for oral drug delivery.

Natural and synthetic materials based CMCh/PVA hydrogels for oxaliplatin delivery: Fabrication, characterization, In-Vitro and In-Vivo safety profiling.

In this study, the chemically crosslinked hydrogels of carboxymethyl chitosan and polyvinyl alcohol were fabricated by the free radical polymerization. Successful polymerization was confirmed by Fourier transform infrared spectroscopy, while x-ray diffraction, thermogravimetric analysis, and differential scanning calorimetric measurements helped in investigating crystallinity and thermal behavior of the products. Morphological characterization was performed by scanning electron microscopy. The increased incorporation of carboxymethyl chitosan and polyvinyl alcohol enhanced the swelling, drug loading, and in-vitro drug release while crosslinking agent acted inversely. The blanked hydrogels were cytocompatible while oxaliplatin loaded hydrogels showed dose-dependent controlled cytotoxicity against HCT-116 and MCF-7. Oral biocompatibility in albino rabbits showed that the hydrogel suspension was tolerable up to 3600 mg/kg as no toxic or histopathological changes were observed upon comparison with the control group. Results of the studies confirmed that the developed hydrogels can be a potential candidate for controlled oxaliplatin delivery and targeting in cancer therapy.

Evaluation of different Pakistani medicinal plants for inhibitory potential against Echis carinatus induced Phospholipase A2 toxicity.

Medicinal plants of Pakistan are known for their curative properties against snake bite as rural people have been using natural herbs for such injuries for hundreds to thousands of years. People of rural areas of Pakistan are prone to snakebite, and on the whole death due to snakebite has been increasing worldwide. The objective of this study was to test the neutralizing potential of 17 Pakistani medicinal plant extracts against phospholipase A2 activity in Echis carinatus venom. Plant material was extracted by simple maceration and fractionation of active plant extracts. Venom was collected by manual massage of the venom glands. The PLA2 enzymatic assay was performed to map out the venomous activity of Echis carinatus envenomation. Snake venom released fatty acids at different concentrations (0.1-5 mg/ml) of venom in a dose-dependent manner. Reduction of pH by 01 correlated with 133 µmol of fatty acids released at 5mg/ml of venom. All plants extract inhibited PLA2 activity, however, Curcuma longa, Citrullus colocynthis and Rubia cordifolia inhibited maximum of PLA2 activity (⁓78%) comparable to the standard antidote (p>0.5). Medicinal plants possess secondary metabolites and many active compounds that may have neutralizing or inhibiting properties against the PLA2 activity of Echis venom. Further studies such as compound analysis could provide an alternative against snakebites injuries resulting from Echis carinatus venom.