Safe Formulation Research Articles

Unraveling the Rank-One Solution Mystery of Robust MISO Downlink Transmit Optimization: A Verifiable Sufficient Condition via a New Duality Result

This paper concentrates on a robust transmit optimization problem for the multiuser multi-input single-output (MISO) downlink scenario and under inaccurate channel state information (CSI). This robust problem deals with a general-rank transmit covariance design, and it follows a safe rate-constrained formulation under spherically bounded CSI uncertainties. Curiously, simulation results in previous works suggested that the robust problem admits rank-one optimal transmit covariances in most cases. Such a numerical finding is appealing because transmission with rank-one covariances can be easily realized by single-stream transmit beamforming. This gives rise to a fundamentally important question, namely, whether we can theoretically identify conditions under which the robust problem admits a rank-one solution. In this paper, we identify one such condition. Simply speaking, we show that the robust problem is guaranteed to admit a rank-one solution if the CSI uncertainties are not too large and the multiuser channel is not too poorly conditioned. To establish the aforementioned condition, we develop a novel duality framework, through which an intimate relationship between the robust problem and a related maximin problem is revealed. Our condition involves only a simple expression with respect to the multiuser channel and other system parameters. In particular, unlike other sufficient rank-one conditions that have appeared in the literature, ours is verifiable. The application of our analysis framework to several other CSI uncertainty models is also discussed.

A Combination of Podophyllotoxin and Rutin Attenuates Radiation Induced Gastrointestinal Injury by Negatively Regulating NF-κB/p53 Signaling in Lethally Irradiated Mice.

Development of an effective radio protector to minimise radiation-inflicted damages have largely failed owing to inherent toxicity of most of the agents examined so far. This study is centred towards delivering protection to lethally irradiated mice by pre-administration of a safe formulation G-003M (combination of podophyllotoxin and rutin) majorly through regulation of inflammatory and cell death pathways in mice. Single intramuscular dose of G-003M injected 60 min prior to 9 Gy exposure rescued 89% of whole body lethally irradiated C57BL/6J mice. Studies have revealed reduction in radiation induced reactive oxygen species (ROS), nitric oxide (NO) generation, prostaglandin E2 (PGE2) levels and intestinal apoptosis in G-003M pre-treated mice intestine. Restricted nuclear translocation of redox-sensitive Nuclear factor-κB (NF-κB) and subsequent downregulation of cyclo-oxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS; EC 1.14.13.39) and tumor necrosis factor (TNF-α) levels demonstrated the anti-inflammatory effect that G-003M exerts. Support to early hematopoietic recovery was exhibited through G-003M mediated induction of granulocyte colony stimulating factor (G-CSF) and interleukin (IL-6) levels in lethally irradiated mice. Considerable attenuation in radiation induced morphological damage to the intestinal villi, crypts and mucosal layers was observed in G-003M pre-treated mice. Additionally, our formulation did not reduce the sensitivity of tumor tissue to radiation. Altogether, these results suggest that G-003M ameliorates the deleterious effects of radiation exposure by minimising ROS and NO generation and effectively regulating inflammatory and cell death pathways. Mechanism of protection elucidated in the current study demonstrates that G-003M can be used as a safe and effective radio protective agent in radiotherapy for human application.

Oral Tocofersolan Corrects or Prevents Vitamin E Deficiency in Children With Chronic Cholestasis.

D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe to provide an orally bioavailable source of vitamin E in children with cholestasis. The aim was to analyze the safety/efficacy of Vedrop in a large group of children with chronic cholestasis. Two hundred seventy-four children receiving Vedrop for vitamin E deficiency or for its prophylaxis were included from 7 European centers. Median age at treatment onset was 2 months and median follow-up was 11 months. Vedrop was prescribed at a daily dose of 0.34 mL/kg (25 IU/kg) of body weight. Three methods were used to determine a sufficient serum vitamin E status: vitamin E, vitamin E/(total cholesterol), vitamin E/(total cholesterol + triglycerides). Before Vedrop therapy, 51% of children had proven vitamin E deficiency, 30% had normal vitamin E status and 19% had an unknown vitamin E status. During the first months of treatment, vitamin E status was restored in the majority of children with insufficient levels at baseline (89% had a normal status at 6 months). All children with a normal baseline vitamin E status had a normal vitamin E status at 6 months. Among children with an unknown vitamin E status at baseline, 93% had a normal vitamin E status at 6 months. A sufficient vitamin E status was observed in 80% of children with significant cholestasis (serum total bilirubin >34.2 μmol/L). No serious adverse reaction was reported. Vedrop seems a safe and effective oral formulation of vitamin E that restores and/or maintains sufficient serum vitamin E level in the majority of children with cholestasis, avoiding the need for intramuscular vitamin E injections.

Ex-vivo complexation, skin permeation, interaction and cytodermal toxicity studies of p-tertbutylcalix[4]arene nanoemulsion for radiation decontamination

Aimsp-tertbutylcalix[4]arene loaded nanoemulsion has been designed, characterized and evaluated for skin decontamination of radionuclides of interest in nuclear and radiological emergencies. Further, nanoemulsion was evaluated for Ex-vivo complexation, skin permeation, interaction and cytodermal toxicity. Materials and methodsEx-vivo skin complexation studies were conducted using High-resolution sector field inductively coupled plasma mass spectroscopy (HR-SF-ICPMS). Skin studies at dermal and cyto-dermal level have been carried out using techniques such as florescence microscopy, Differential scanning calorimetry (DSC), Flow cytometry, Confocal microscopy, Prestoblue and Comet assay. Key findingsHR-SF-ICPMS study confirmed >95% complexation of surrogate nuclides of thallium and Iodine applied on excised rat skin mounted over Franz diffusion cell. Temporal analysis of aliquots obtained from Franz diffusion cell using UV–Vis absorption spectroscopy indicated that only 3.37% of formulation permeates through the skin. Skin penetration study of rhodamine 123 nanoemulsion carried out using florescence microscopy confirmed that formulation remains localised in epidermis of rat skin. DSC data confirmed skin compatibility of nanoemulsion, as no lipid extraction was observed from skin. In-vitro cell viability and cellular uptake assays performed on human skin fibroblasts prove no cellular uptake and cytotoxic effects. Comet assay, cell cycle arrest, and apoptosis-inducing mechanistic studies prove that prepared nanoemulsion is safe at cellular level. SignificanceTaken together, data indicate that p-tertbutylcalix[4]arene nanoemulsion is both effective and safe formulation to use on skin for radio-decontamination.

Impact of additives on the formation of protein aggregates and viscosity in concentrated protein solutions

In concentrated protein solutions attractive protein interactions may not only cause the formation of undesired aggregates but also of gel-like networks with elevated viscosity. To guarantee stable biopharmaceutical processes and safe formulations, both phenomenons have to be avoided as these may hinder regular processing steps. This work screens the impact of additives on both phase behavior and viscosity of concentrated protein solutions. For this purpose, additives known for stabilizing proteins in solution or modulating the dynamic viscosity were selected. These additives were PEG 300, PEG 1000, glycerol, glycine, NaCl and ArgHCl. Concentrated lysozyme and glucose oxidase solutions at pH 3 and 9 served as model systems. Fourier-transformed-infrared spectroscopy was chosen to determine the conformational stability of selected protein samples. Influencing protein interactions, the impact of additives was strongly dependent on pH. Of all additives investigated, glycine was the only one that maintained protein conformational and colloidal stability while decreasing the dynamic viscosity. Low concentrations of NaCl showed the same effect, but increasing concentrations resulted in visible protein aggregation.

Pharmaceutical Standardization of Saptamrita Lauha

Shalakya Tantra is a one of the branch of Ashtanga Ayurveda and Netra Chikitsa is a part of Shalakya Tantra. There are so many formulations are mentioned in the treatment of Netra Roga by oral route as well as external application, Saptamrita Lauha is one of them. It is a very popular, very safe and effective formulation for eye diseases. In Ayurveda classics there are so many references are available for Saptamrita Lauha. These formulation are mainly described in Netra Roga and Shoola Roga in almost all the books. In majority references Saptamrita Lauha powder is taken with Anupana or Sahapana of honey and ghee. Sundar Ayurveda Teaching Pharmacy is also manufacturing many batches of Saptamrita Lauha with the reference from Bheshaja Samhita, chapter 4/54, Loha and Mandura Kalpana and follow the in house quality control parameters to standardized the medicine in large scale production. The particle size of Saptamrita Lauha is 3.2 µm to 3.8 µm, pH from 6.0 to 6.9, loss on drying from 1.2 % to 1.8%, ash value 16.2 %w/w to 24.5 %w/w, acid insoluble ash value from 2.6 %w/w to3.6 %w/w, alcohol soluble extractive value from 42.9% v/w to 47.7 %v/w, water soluble extractive value from 21.1 % to 26.8%. Phyto-chemical screening of Saptamrita Lauha shows Glycoside, Amino acid, Protein, Carbohydrate, Flavanoid, Tannin, Steroid, Saponin and Alkaloid were present in all batches. On the basis of this study it’s clear that, if we follow the same procedure with authentic drugs then large scale production also having Quality assurance.

Enhanced stimulation of anti-breast cancer T cells responses by dendritic cells loaded with poly lactic-co-glycolic acid (PLGA) nanoparticle encapsulated tumor antigens.

BackgroundDeveloping safe and effective cancer vaccine formulations is a primary focus in the field of cancer immunotherapy. Dendritic cells (DC) are currently employed as cellular vaccine in clinical trials of tumor immunotherapy. Recognizing the critical role of DCs in initiating anti-tumor immunity has resulted in the development of several strategies that target vaccine antigens to DCs to trigger anti-tumor T cell responses. To increase the efficiency of antigen delivery systems for anti-tumor vaccines, encapsulation of tumor-associated antigens in polymer nanoparticles (NPs) has been established.MethodsIn this study, the effect of tumor lysate antigen obtained from three stage III breast cancer tissues encapsulated within PLGA NPs to enhance the DC maturation was investigated. The T-cell immune response activation was then fallowed up. Fresh breast tumors were initially used to generate tumor lysate antigens containing poly lactic-co-glycolic acid (PLGA) NP. The encapsulation efficiency and release kinetics were profiled. The efficiency of encapsulation was measured using Bradford protein assays measuring the dissolved NPs. The stability of released antigen from NPs was verified using SDS-PAGE. To evaluate the hypothesis that NPs enhances antigen presentation, including soluble tumor lysate, tumor lysate containing NPs and control NPs the efficiency of NP-mediated tumor lysate delivery to DCs was evaluated by assessing CD3+ T-cell stimulation after T cell/and DCs co-culture.ResultsThe rate of encapsulation was increased by enhancing the antigen concentration of tumor lysate. However, increasing the antigen concentration diminished the encapsulation efficiency. In addition, higher initial protein contenting NPs led to a greater cumulative release. All three patients released variable amounts of IFN-γ, IL-10, IL-12 and IL-4 in response to re-stimulation. T cells stimulated with lysate-pulsed DCs induced a substantial increase in IFN-γ and IL-12 production. We demonstrated that NPs containing tumor lysate can induce maturation and activation of DCs, as antigen alone does.ConclusionPLGA-NPs are attractive vehicles for protein antigen delivery which effectively induce stimulation and maturation of DCs, allowing not only an enhanced antigen processing and immunogenicity or improved antigen stability, but also the targeted delivery and slow release of antigens.

High-performance thin-layer chromatography based concurrent estimation of biomarkers ent-phyllanthidine and rutin in the dried aerial parts of Flueggea virosa

The biomarkers are needed to be defined for standardization purposes so that safe and effective herbal formulations can be catered to the society. There is an urgent need for statistical support of herbal drugs because most of the herbal products are still used in the non-standardized form. This study is based on the development of a simple and sensitive RP-HPTLC method for concurrent estimation of two biomarkers ent-phyllanthidine and rutin in the methanol extract of aerial parts of Flueggea virosa. The developed method was found to be simple, economic and sensitive. Separation and quantification were performed with acetonitrile: water (4:6V/V) used as the mobile phase on glass-backed RP-HPTLC plate. Detection of absorption maxima and quantification was done at 310nm of UV region. The developed chromatographic system was found to give a sharp band for ent-phyllanthidine and rutin at Rf 0.73±0.01 and 0.68±0.01, respectively. The linearity ranges for ent-phyllanthidine, and rutin were found to be 200–1600ngband−1 and 100–1400ngband−1, respectively, with correlation coefficients (r2 values) of 0.998 and 0.997, respectively. The percentage of ent-phyllanthidine and rutin was found to be 9.121±0.02% and 1.018±0.04% (w/w), respectively. The resolution of bands and separation of constituents in FVME exhibited the perfect optimization of the developed method. The validation statistics supports the proposed method for standardizing crude drugs as well as formulations of a natural product containing ent-phyllanthidine and rutin.

Iron Fortification of Foods for Infants and Children in Low-Income Countries: Effects on the Gut Microbiome, Gut Inflammation, and Diarrhea.

Iron deficiency anemia (IDA) is common among infants and children in Sub-Saharan Africa and is a leading contributor to the global burden of disease, as well as a hindrance to national development. In-home iron fortification of complementary foods using micronutrient powders (MNPs) effectively reduces the risk for IDA by ensuring that the iron needs of infants and young children are met without changing their traditional diet. However, the iron dose delivered by MNPs is high, and comparable on a mg iron per kg body weight to the supplemental doses (2 mg/kg) typically given to older children, which increases diarrhea risk. In controlled studies, iron-containing MNPs modestly increase risk for diarrhea in infants; in some cases, the diarrhea is severe and may require hospitalization. Recent in vitro and in vivo studies provide insights into the mechanism of this effect. Provision of iron fortificants to school-age children and iron-containing MNPs to weaning infants decreases the number of beneficial ‘barrier’ commensal gut bacteria (e.g., bifidobacteria), increases the enterobacteria to bifidobacteria ratio and abundances of opportunistic pathogens (e.g., pathogenic Escherichia coli), and induces gut inflammation. Thus, although iron-containing MNPs are highly effective in reducing IDA, they may increase gastrointestinal morbidity in infants, and safer formulations are needed.

THE PURVIEW OF PHYTOTHERAPY IN THE MANAGEMENT OF KIDNEY DISORDERS: A SYSTEMATIC REVIEW ON NIGERIA AND SOUTH AFRICA.

Background:The kidney is tasked with a number of metabolic functions in the body. In its role as a detoxifier and primary eliminator of xenobiotics, it becomes vulnerable to developing injuries. Currently, over 1 million people in the world are living on renal replacement therapies (RRTs). The case in sub-Sahara African countries like Nigeria and South Africa is not any better than the global trend.Materials and Methods:A systematic review of medicinal plants used in the treatment of kidney disorders was conducted. Information were gathered from published scientific journals, books, reports from national, regional and international institutions, conference proceedings and other high profile intellectual resources. MeSH words like ‘prevalence of kidney disorders in Africa’, ‘renal replacement therapy’, ‘nephrotoxins or nephrotoxicants’, ‘nephroprotective plants’, ‘nephroprotective plants in Nigeria or South Africa’ and ‘nephroprotective phytocompounds’ were used to retrieve information from online databases (Google, Pubmed, MEDLINE, Science Direct, Scopus and SID).Results:Interestingly, our findings revealed that phytotherapy has emerged and is being employed to protect renal functions and delay progression of renal pathological conditions into end episodes where the last resort is RRT. In fact, in recent times, Phytotherapists are not only interested in developing relatively safe, more affordable, easily accessible and potent nephroprotective formulations but also increasing awareness on the prevalence of the disease and educating the populace on the probable preventive measures. More importantly, efforts at scientifically elucidating the pharmacological efficacy of the identified nephroprotective plants yet to be validated must be intensified through informed expert opinions. Till date, there is paucity of information on the concept of nephroprotection in most developing countries where kidney disorder is a major threat. Although, the concept is just emerging in South Africa, evidences have given credence to its application in complementary and alternative system of medicine in Nigeria.Conclusion:This review, therefore, reawaken researchers’ consciousness in the continuous search for auspicious nephroprotective plants that could potentially be excellent candidates in developing new lead drugs to manage and treat renal disorders.

DR5 mAb-conjugated, DTIC-loaded immuno-nanoparticles effectively and specifically kill malignant melanoma cells in vivo.

We combined chemo- and immunotherapies by constructing dual therapeutic function immuno-nanoparticles (NPs) consisting of death receptor 5 monoclonal antibody (DR5 mAb)-conjugated nanoparticles loaded with dacarbazine (DTIC) (DTIC-NPs-DR5 mAb). We determined the in vivo targeting specificity of DTIC-NPs-DR5 mAb by evaluating distribution in tumor-bearing nude mice using a real-time imaging system. Therapeutic efficacy was assessed in terms of its effect on tumor volume, survival time, histomorphology, microvessel density (MVD), and apoptotic index (AI). Systemic toxicity was evaluated by measuring white blood cells (WBC) counts, alanine aminotransferase (ALT) levels, and creatinine clearance (CR).In vivo and ex vivo imaging indicates that DR5 mAb modification enhanced the accumulation of NPs within the xenograft tumor. DTIC-NPs-DR5 mAb inhibited tumor growth more effectively than DTIC or DR5 mAb alone, indicating that combining DTIC and DR5 mAb through pharmaceutical engineering achieves a better therapeutic effect. Moreover, the toxicity of DTIC-NPs-DR5 mAb was much lower than that of DTIC, implying that DR5 mAb targeting reduces nonspecific uptake of DTIC into normal tissue and thus decreases toxic side effects. These results demonstrate that DTIC-NPs-DR5 mAb is a safe and effective nanoparticle formulation with the potential to improve the efficacy and specificity of melanoma treatment.

Design and Evaluation of Ophthalmic Delivery of Bepotastine Besilate From Eye Drop

Introduction: The purpose of present study was to design and evaluate bepotastine besilate ophthalmic solution 1.5% to develop a stable formulation using buffering agent, tonicity modifier and preservative. Method: In this study the concentration of preservative and tonicity modifier concentration are adjusted in such a way so that the final formulation will have least concentration of preservative still it will be protected from microorganisms and isotonic so that after instillation when formulation will come in contact with tissues there should not be any swelling, contraction or discomfort. Result: The preservative content was selected in the range of 0.002– 0.012% and tonicity modifier in the range of 0.45–0.9%. Bepotastine besilate ophthalmic solution 1.5% filled in LDPE container having fill volume 5 mL is clear, colourless solution having pH range 6.8–7.0, drop size of 38.6 μl and % water loss after 3 months as 1.9748%. The percent purity of bepotastine besilate and preservative was determined using RP-HPLC method was found to be 100.50 and 51.648% with % RSD as 0.84 and 0.65% respectively. The samples of the formulation also subjected to stability as per ICH guidelines and 6 months data was generated. Draize test protocol was also followed to study invivo eye irritancy of the formulation to produce a safe and effective formulation. Conclusion: Laboratory prepared formulation of bepotastine besilate ophthalmic solution 1.5% has showed good stability at both 25°C and 40°C as the drug and preservative content was within the accepted range. Key words: Bepotastine besilate, Benzalkonium chloride eye drop, Preservative, Ophthalmic preparation, Stability study, Isotonicity.

Adolescent fatigue: Is intravenous iron a better solution?

Adolescent fatigue: Is intravenous iron a better solution?

English

Despite advances in the research on new antifungal agents, Amphotericin B (AmB) is still considered as the antifungal of choice for treating most systemic mycoses due to its potency and broad-spectrum action. However, this drug has limited use because of its toxic effects on kidneys, liver and blood. The search for new and safe formulations of AmB is essential because of the emergence of antifungal resistance to other drugs and the increased number of immunosuppressed patients. Nanoparticles are a promising alternative towards achieving lower toxicity and improved pharmacokinetic properties. This study is a literature review of the use of AmB and the toxicity of formulations. Some of the current new formulations show some advantageous characteristics as compared to AmB. However, there is still need for a continued search for an effectively improved formulation. Key words: Amphotericin B, toxicity, nanotechnology, pharmaceutical technology.

γH2AX formation kinetics in PBMCs of rabbits exposed to acute and fractionated radiation and attenuation of focus frequency through preadministration of a combination of podophyllotoxin and rutin hydrate

DNA damage can be assessed by the quantitation of γH2AX foci that form at DSB sites. This study examines the generation and persistence of γH2AX foci, variability in foci size after acute and fractionated radiation exposure, and the effect of pretreatment with a safe radioprotective formulation termed G-003M on foci generation and persistence. G-003M contains a combination of podophyllotoxin and rutin hydrate, and was administered intramuscularly to rabbits 1 hr prior to Co(60) gamma irradiation. Rabbits were assigned to one of the following treatment groups: untreated, G-003M alone, irradiated (single dose 8 Gy, fractionated 2 Gy/day for 4 days or single dose 2 Gy) or G-003M preadministration followed by radiation exposure. Foci continuously persisted for a week in peripheral blood mononuclear cells of rabbits exposed to a single 8 Gy dose. However, the number of foci gradually decreased after reaching a maximum at 1 h. In rabbits exposed to fractionated radiation, foci detected 1 hr after the final exposure were significantly larger (P < 0.001) than in rabbits exposed to a single 8 Gy dose, but disappeared completely after 24 h. In both groups, foci reappeared on days 11-15 in terminally ill animals. G-003M pretreatment significantly (P < 0.05) attenuated the formation of γH2AX foci in all irradiated rabbits. This study reveals that γH2AX focus assessment could be used to confirm radiation exposure, that focus size reflects the type of radiation exposure (acute or fractionated), that the re-appearance of foci is a strong indicator of imminent death in animals, and that G-003M provides protection against radiation. Environ. Mol. Mutagen. 57:455-468, 2016. © 2016 Wiley Periodicals, Inc.

The Isothiocyanate Isolated from Moringa oleifera Shows Potent Anti-Inflammatory Activity in the Treatment of Murine Subacute Parkinson's Disease.

The present study was aimed at estimating a possible neuroprotective effect of glucomoringin (GMG) [4-(α-L-rhamnopyranosyloxy)benzyl glucosinolate] bioactivated with the enzyme myrosinase to form the corresponding isothiocyanate [4-(α-L-rhamnopyranosyloxy)benzyl C; moringin] in the treatment or prevention of Parkinson's disease (PD). In this study, the beneficial effects of moringin were compared with those of pure GMG, not enzymatically activated, in an in vivo experimental mouse model of subacute PD. Subacute PD was induced in C57BL/6 mice by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Mice were pretreated daily for 1 week with moringin (10 mg/kg +5 μL myrosinase/mouse) and with GMG (10 mg/kg). Behavioral evaluations were also performed to assess motor deficits and bradykinesia in MPTP mice. Besides, assuming that pretreatment with moringin could modulate the triggering of inflammatory cascade with a correlated response, we tested its in vitro anti-inflammatory activity by using a model of RAW 264.7 macrophages stimulated with lipopolysaccharide. Achieved results in vivo showed a higher efficacy of moringin compared with GMG not only to modulate the inflammatory pathway but also oxidative stress and apoptotic pathways. In addition, the greater effectiveness of moringin in countering mainly the inflammatory pathway has been corroborated by the results obtained in vitro. The relevance and innovation of the present study lie in the possible use of a safe formulation of a bioactive compound, resulting from exogenous myrosinase hydrolysis of the natural phytochemical GMG, which can be used in clinical practice as a useful drug for the treatment or prevention of PD.

Paediatric Drug Development and Formulation Design\u2014a European Perspective

The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off-label or unlicensed drugs. As off-label and unlicensed drug use are associated with a greater risk for harm than on-label drug use, a range of global initiatives have been developed to realize “better” medicines for children. This review describes the challenges and achievements of the European Union to realize this goal, with a focus on paediatric drug development and formulation design. In 2007, a European Paediatric Regulation was installed enforcing companies to consider children in the early development of drugs with a new drug substance, for a new indication or with a new route of administration. The Regulation, e.g. requires companies to develop a paediatric investigation plan discussing the proposed clinical trials in children of different ages and the formulations for future marketing. Since 2013, the pharmaceutical design of any newly marketed paediatric drug should comply with the “Guideline on the Pharmaceutical Development of Medicines for Paediatric Use.” Companies should, e.g. justify the route of administration, dosage form, formulation characteristics, safety of excipients, dosing frequency, container closure system, administration device, patient acceptability and user information. In this review, the guideline’s key aspects are discussed with a focus on novel formulations such as mini-tablets and orodispersible films, excipients with a potential risk for harm such as azo dyes and adequate user instructions.

Over-the-counter treatments for acne and rosacea.

Acne and rosacea are common inflammatory processes historically classified in the same disease category, but evolving understanding of their disparate pathophysiology and exacerbating factors have generated an enormous armamentarium of therapeutic possibilities. Patients seek over-the-counter therapies first when managing cutaneous disease; therefore, this review defines ingredients considered to be effective over-the-counter acne and rosacea products, their mechanisms, and safe formulations, including botanical components, oral supplements, and other anecdotal options in this vast skin care domain.

Clinical application of intravenous immunoglobulin

Intravenous immunoglobulin (IVIG) is safe and effective concentration formulation which is obtained from the plasma of health adults.Domestic IVIG was used in clinical since 1979 by Liao Qingkui, who are pediatric doctor form West China Second Hospital. Researches on clinical applications of IVIG are quickly developed at home and abroad, which now become the indispensable treatment for primary and secondary immunodeficiency diseases, autoimmune diseases, infectious disease(especially for virus), stem cell or organ transplantation and ICU areas.Treatment dose and course are administered accordding to individuals and pharmacokinetic characteristics of IVIG, immunoglobulin rose to peak of drug concentration quickly, and recovery to the original level of plasma after 3-4 weeks.Common therapeutic dose of IVIG recommended by the literature were 400 mg/(kg·per time), 3-5 d, or 1 000 mg/(kg·per time), 2 d, or 2 000 mg/(kg·per time), 1 d, which were usually used for idiopathic thrombocytopenic purpura, Kawasaki disease patients.Treatment perscription of 200-600 mg/(kg·per time), 1 d, and once every 2-6 weeks are used for immunodeficiency diseases and infections.Now, the clinical application of IVIG was reviewed. Key words: Intravenous infection; Immunoglobulin; Clinical application

A nanotechnology based new approach for chemotherapy of Cutaneous Leishmaniasis: TIO2@AG nanoparticles – Nigella sativa oil combinations

Since toxicity and resistance are the major drawbacks of current antileishmanial drugs, studies have been recently focused on combination therapy in fight against leishmaniasis. Combination therapy generally provides opportunity to decrease toxicity of applied agents and enhance their antimicrobial performance. Moreover, this method can be effective in preventing drug resistance. Highly antileishmanial effects of silver doped titanium dioxide nanoparticles (TiAgNps) and Nigella sativa oil were demonstrated in previous studies. However, toxicity is still an important factor preventing use of these molecules in clinic. By considering high antileishmanial potential of each agent and basic principles of combination therapy, we propose that use of combinations including non-toxic concentrations of TiAgNps and N. sativa oil may compose more effective and safer formulations against Leishmania parasites. Therefore, the main goal of the present study was to investigate antileishmanial effects of non-toxic concentrations of TiAgNps and Nigella sativa oil combinations on promastigote and amastigote-macrophage culture systems and also to develop nanotechnology based new antileishmanial strategies against Cutaneous Leishmaniasis. Numerous parameters such as proliferation, metabolic activity, apoptosis, amastigote-promastigote conversion, infection index analysis and nitric oxide production were used to detect antileishmanial efficacies of combinations. Investigated all parameters demonstrated that TiAgNps-N. sativa oil combinations had significant antileishmanial effect on each life forms of parasites. Tested combinations were found to decrease proliferation rates of Leishmania tropica promastigotes in a range between 1,5–25 folds and metabolic activity values between 2 and 4 folds indicating that combination applications lead to virtually inhibition of promastigotes and elimination of parasites were directly related to apoptosis manner. TiAgNps-N. sativa combinations also demonstrated killing effects on L. tropica amastigotes by decreasing infection index values of macrophages 5–20 folds, inhibiting their metabolic activities up to 5 fold, preventing amastigote-promastigote conversion and producing high amounts of nitric oxide. All these results emphasize high potential of TiAgNps-N. sativa oil combinations as new, safer and effective antileishmanial formulations against Cutaneous Leishmaniasis.