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1.
J Nanobiotechnology ; 19(1): 106, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858436

RESUMO

As a neglected tropical disease, Leishmaniasis is significantly instigating morbidity and mortality across the globe. Its clinical spectrum varies from ulcerative cutaneous lesions to systemic immersion causing hyperthermic hepato-splenomegaly. Curbing leishmanial parasite is toughly attributable to the myriad obstacles in existing chemotherapy and immunization. Since the 1990s, extensive research has been conducted for ameliorating disease prognosis, by resolving certain obstacles of conventional therapeutics viz. poor efficacy, systemic toxicity, inadequate drug accumulation inside the macrophage, scarce antigenic presentation to body's immune cells, protracted length and cost of the treatment. Mentioned hurdles can be restricted by designing nano-drug delivery system (nano-DDS) of extant anti-leishmanials, phyto-nano-DDS, surface modified-mannosylated and thiolated nano-DDS. Likewise, antigen delivery with co-transportation of suitable adjuvants would be achievable through nano-vaccines. In the past decade, researchers have engineered nano-DDS to improve the safety profile of existing drugs by restricting their release parameters. Polymerically-derived nano-DDS were found as a suitable option for oral delivery as well as SLNs due to pharmacokinetic re-modeling of drugs. Mannosylated nano-DDS have upgraded macrophage internalizing of nanosystem and the entrapped drug, provided with minimal toxicity. Cutaneous Leishmaniasis (CL) was tackling by the utilization of nano-DDS designed for topical delivery including niosomes, liposomes, and transfersomes. Transfersomes, however, appears to be superior for this purpose. The nanotechnology-based solution to prevent parasitic resistance is the use of Thiolated drug-loaded and multiple drugs loaded nano-DDS. These surfaces amended nano-DDS possess augmented IC50 values in comparison to conventional drugs and un-modified nano-DDS. Phyto-nano-DDS, another obscure horizon, have also been evaluated for their anti-leishmanial response, however, more intense assessment is a prerequisite. Impoverished Cytotoxic T-cells response followed by Leishmanial antigen proteins delivery have also been vanquished using nano-adjuvants. The eminence of nano-DDS for curtailment of anti-leishmanial chemotherapy and immunization associated challenges are extensively summed up in this review. This expedited approach is ameliorating the Leishmaniasis management successfully. Alongside, total to partial eradication of this disease can be sought along with associated co-morbidities.

2.
J Microencapsul ; : 1-16, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33689550

RESUMO

This study aimed to develop and optimise a Curcumin-loaded SLNs (C-SLNs) patch through a new approach for transdermal delivery. C-SLNs were optimised through the response surface central composite design using the modified injection method. Optimised C-SLNs were loaded into a polyvinyl alcohol-based patch through the backing membrane method. Compatibility studies (FTIR, XRPD), in vitro release, ex vivo skin permeation, accelerated stability, and evaluation studies of the patch were also performed. Prepared C-SLNs exhibited average particle diameter of 170 ± 2 nm with an encapsulation efficiency of 90 ± 3.5% (w/w) while SEM illustrated spherical shape of particles. In vitro release data ensured a sustained release for up to 72 hours. The enhancement ratio of C-SLNs based patch with permeation enhancer (PE) was high up to 6.5 folds as compared to patch without PE. It is concluded that the modified injection method is simple, economical, and less time consuming for the development of C-SLNs patch for the transdermal route.

3.
Drug Dev Ind Pharm ; 47(3): 440-453, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33615936

RESUMO

OBJECTIVE: The purpose of this study was to develop novel carbopol-based miltefosine-loaded transfersomal gel (HePCTG) for the treatment of cutaneous leishmaniasis (CL) via efficient targeting of leishmania infected macrophages. METHODS: Miltefosine-loaded transfersomes (HePCT) were prepared by ethanol injection method followed by their incorporation into carbopol gel to form HePCTG. The prepared HePCT were assessed for physicochemical properties including mean particle size, polydispersity index, zeta potential, entrapment efficiency, morphology, and deformability. Similarly, HePCTG was evaluated for physiochemical and rheological attributes. The in vitro release, skin permeation, skin irritation, anti-leishmanial activity, and in vivo efficacy in BALB/c mice against infected macrophages were also performed for HePCT. RESULTS: The optimized HePCT displayed a particle size of 168 nm with entrapment efficiency of 92%. HePCTG showed suitable viscosity, pH, and sustained release of the incorporated drug. Furthermore, HePCT and HePCTG demonstrated higher skin permeation than drug solution. The results of macrophage uptake study indicated improved drug intake by passive diffusion. The lower half maximal inhibitory concentration value, selectivity index and higher 50% cytotoxic concentration  value of HePCT compared to that of HePC solution demonstrated the improved anti-leishmanial efficacy and non-toxicity of the formulation. This was further confirmed by the notable reduction in parasite load and lesion size observed in in vivo anti-leishmanial study. CONCLUSION: It can be stated that the formulated HePCTG can effectively be used for the treatment of CL.

4.
BMC Infect Dis ; 21(1): 35, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413164

RESUMO

BACKGROUND: Crimean Congo Haemorrhagic Fever (CCHF), a tropically neglected infectious disease caused by Nairovirus, is endemic in low middle-income countries like Pakistan. Emergency health care professionals (HCPs) are at risk of contracting nosocomial transmission of CCHF. We, therefore, aim to analyze the knowledge, attitudes, and perceptions (KAP) of at-risk physicians, nurses, and pharmacists in Pakistan and the factors associated with good KAP. METHOD: A validated questionnaire (Cronbach's alpha 0.71) was used to collect data from HCPs in two CCHF endemic metropolitan cities of Pakistan by employing a cross-sectional study design. For data analysis percentages, chi-square test and Spearman correlation were applied by using SPSS version 22. RESULTS: Of the 478 participants, 56% (n = 268) were physicians, 37.4% (n = 179) were nurses, and 6.5% (n = 31) were pharmacists. The proportion of HCPs with good knowledge, attitude, and perception scores was 54.3%, 81, and 69%, respectively. Being a physician, having more work experience, having a higher age, working in tertiary care settings, were key factors for higher knowledge (p < 0.001). The correlation coefficient showed significant positive correlation between attitude- perception (r = 0.560, p < 0.001). CONCLUSION: We have observed average knowledge of HCPs. Therefore, we recommend time to time education campaigns and workshops in highly endemic CCHF regions to be launched by health ministries and HCPs, in particular nurses, encouraged to follow authentic academic sources of information to prevent nosocomial transmission.


Assuntos
Atitude do Pessoal de Saúde , Febre Hemorrágica da Crimeia , Adolescente , Adulto , Cidades , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Febre Hemorrágica da Crimeia/tratamento farmacológico , Febre Hemorrágica da Crimeia/epidemiologia , Febre Hemorrágica da Crimeia/transmissão , Humanos , Masculino , Pessoa de Meia-Idade , Enfermeiras e Enfermeiros , Paquistão/epidemiologia , Médicos , Inquéritos e Questionários , Adulto Jovem
5.
Int J Pharm ; 593: 120109, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33253802

RESUMO

The purpose of this study was to enhance the anti-leishmanial efficacy of miltefosine (MTF) and reduce its toxic effects by loading it into nanostructured lipid carriers (NLCs). Micro-emulsion technique was used to prepare MTF-loaded NLCs. The optimized NLCs were characterized in terms of various physicochemical parameters including particle size, poly dispersity index (PDI), zeta potential, transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) technique. In vitro and in vivo assays were performed to evaluate the potential of NLCs as an effective nanocarrier system for oral delivery of MTF in Cutaneous Leishmaniasis. The optimized MTF-loaded NLCs exhibited mean particle size of 160.8 ± 5.3 nm with narrow PDI and high incorporation efficiency (IE%) of 96.17 ± 1.3%. MTF-loaded NLCs demonstrated slow release of the incorporated drug as compared to the drug solution. The optimized formulation showed significant decrease in hemolytic potential, 2.5~folds increase in anti-leishmanial efficacy and 6~fold decrease in macrophage cytotoxicity as compared to MTF solution, in vitro. Macrophage uptake study confirmed passive targeting ability of MTF-loaded NLCs. In-vivo analysis demonstrated enhanced anti-leishmanial effect of the MTF-loaded NLCs and better pharmacokinetic profiles with no gastrointestinal (GI) toxicity. NLCs are potential nanocarriers for the oral delivery of MTF with enhanced anti-leishmanial activity, better safety profile and reduced hemolytic potential.

6.
BMC Infect Dis ; 20(1): 874, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228562

RESUMO

BACKGROUND: Pakistan is facing a growing population of people living with human immunodeficiency (HIV). In this randomized controlled trial, we investigate if a pharmacist-led intervention can increase adherence to antiretroviral therapy (ART) for people living with HIV (PLWH). METHODS: Adults with HIV, who have been taking ART for more than 3 months were randomly assigned to receive either a pharmacist-led intervention or their usual care. Measures of adherence were collected at 1) baseline 2) just prior to delivery of intervention and 3) 8 weeks later. The primary outcomes were CD4 cell count and self-reported adherence measured with the AIDS Clinical Trial Group (ACTG) questionnaire. RESULTS: Post-intervention, the intervention group showed a statistically significant increase in CD4 cell counts as compared to the usual care group (p = 0.0054). In addition, adherence improved in the intervention group, with participants being 5.96 times more likely to report having not missed their medication for longer periods of time (p = 0.0086) while participants in the intervention group were 7.74 times more likely to report missing their ART less frequently (p < 0.0001). CONCLUSIONS: The findings support the improvement in ART adherence and HIV management. TRIAL REGISTRATION: The trial is registered with Australian New Zealand Clinical Trials Registry ( ACTRN12618001882213 ). Registered 20 November 2018.

7.
Pharmaceutics ; 12(11)2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33182248

RESUMO

Intricate formulation methods and/or the use of sophisticated equipment limit the prevalence of liposomal dosage-forms. Simple techniques are developed to assemble amphiphiles into globular lamellae while transiting from the immiscible organic to the aqueous phase. Various parameters are optimized by injecting chloroform solution of amphiphiles into the aqueous phase and subsequent removal of the organic phase. Further simplification is achieved by reorienting amphiphiles through a spontaneous phase transition in a swirling biphasic system during evaporation of the organic phase under vacuum. Although the chloroform injection yields smaller Z-average and poly-dispersity-index the spontaneous phase transition method overrides simplicity and productivity. The increasing solid/solvent ratios results in higher Z-average and broader poly-dispersity-index of liposomes under a given set of experimental conditions, and vice versa. Surface charge dependent large unilamellar vesicles with a narrow distribution have poly-dispersity-index < 0.4 in 10 µM saline. As small and monodisperse liposomes are prerequisites in targeted drug delivery strategies, hence the desired Z-average < 200 d.nm and poly-dispersity-index < 0.15 is obtained through the serial membrane-filtration method. Phosphatidylcholine/water 4 µmol/mL is achieved at a temperature of 10°C below the phase-transition temperature of phospholipids, ensuring suitability for thermolabile entities and high entrapment efficiency. Both methods furnish the de-novo rearrangement of amphiphiles into globular lamellae, aiding in the larger entrapped volume. The immiscible organic phase benefits from its faster and complete removal from the final product. High cholesterol content (55.6 mol%) imparts stability in primary hydration medium at 5 ± 3 °C for 6 months in light-protected type-1 glass vials. Collectively, the reported methods are novel, scalable and time-efficient, yielding high productivity in simple equipment.

8.
AAPS PharmSciTech ; 21(7): 275, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033847

RESUMO

In the published manuscript, co-author Sarah Hendrickx name was misspelled and co-author Guy Caljon's last and first names were inadvertently switched.

9.
AAPS PharmSciTech ; 21(6): 222, 2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32748244

RESUMO

The world is facing lockdown for the first time in decades due to the novel coronavirus COVID-19 (SARS-CoV-2) pandemic. This has led to massive global economic disruption, placed additional strain on local and global public health resources and, above all, threatened human health. We conducted a review of peer-reviewed and unpublished data, written in English, reporting on the current COVID-19 pandemic. This data includes previously used strategies against infectious disease, recent clinical trials and FDA-approved diagnostic and treatment strategies. The literature was obtained through a systematic search using PubMed, Web of Sciences, and FDA, NIH and WHO websites. Of the 98 references included in the review, the majority focused on pathogen and host targeting, symptomatic treatment and convalescent plasma utilization. Other sources investigated vaccinations in the pipeline for the possible prevention of COVID-19 infection. The results demonstrate various conventional as well as potentially advanced in vitro diagnostic approaches (IVD) for the diagnosis of COVID-19. Mixed results have been observed so far when utilising these approaches for the treatment of COVID-19 infection. Some treatments have been found highly effective in specific regions of the world while others have not altered the disease process. The responsiveness of currently available options is not conclusive. The novelty of this disease, the rapidity of its global outbreak and the unavailability of vaccines have contributed to the global public's fear. It is concluded that the exploration of a range of diagnostic and treatment strategies for the management of COVID-19 is the need of the hour.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Pandemias/prevenção & controle , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Antivirais/uso terapêutico , Humanos , Imunização Passiva/tendências , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas de Amplificação de Ácido Nucleico/tendências , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/tendências
10.
Int J Clin Pharm ; 42(5): 1311-1318, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32857257

RESUMO

Background The list of oral and expensive chemotherapy agents has lengthened over the last few years and has created unique medication adherence concerns. In a real-life setting, patients often do not take their medications as prescribed. This pattern is associated with poor outcomes and increased health care costs. Objectives To estimate the adherence to oral anticancer chemotherapies and to determine the economic burden of unused medicines due to patients' death. Setting Alsace (France). Method This retrospective study was carried out by using ERASME, an Insurance Healthcare database. Main outcome measures Adherence was calculated using medication possession ratio and economic impact using prescription refill data. Results 10,734 patients were treated with oral anticancer medicines (cytotoxic agents, hormonal and targeted therapies). Averaged adherence of 0.86 was observed although it varied significantly between subclasses (cytotoxic agents: 0.69 ± 0.14, hormonal therapy: 0.91 ± 0.17 and targeted therapy: 0.79 ± 0.17). 1631 patients died during the study period. The expenses related to unused chemotherapies amounted to €152,175. Conclusions Our data showed that overall adherence to oral anticancer medicines was above the acceptable limit of adherence of 80% with a marked graduation in values between cytotoxic agents, hormonal and targeted therapies. These statistical significant differences in medication possession ratio could be related to the intrinsic toxicity of the three subclasses of molecules, their tolerance and adverse effects. To limit the cost associated with unused medicines, interventions such as dispensing expensive oral anticancer chemotherapies per unit over shorter periods and not only on monthly intervals could be implement.

11.
AAPS PharmSciTech ; 21(5): 185, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632542

RESUMO

The present study aimed to develop, characterize and evaluate the amphotericin B-loaded nanostructured lipid carriers (AmB-NLCs) for topical treatment of cutaneous leishmaniasis (CL) and vulvovaginal candidiasis (VVC). AmB-NLCs were characterized for particle size, zeta potential, encapsulation efficiency and surface morphology. Prepared NLCs were also characterized for in vitro drug release, ex vivo skin permeation and deposition before evaluating their in vitro and in vivo efficacy. Cytotoxicity of NLCs was assessed on MRC-5 cells, whereas skin irritation potential was evaluated in vivo using rats. Significant accumulation of drug in to the skin supported the topical application potential of drug-loaded NLCs. Encapsulation of AmB in NLCs resulted in enhanced in vitro potency against promastigotes and intracellular amastigotes of L. major JISH 118 (IC50 ± SEM = 0.02 ± 0.1 µM for both) compared with free drug (IC50 ± SEM = 0.15 ± 0.2 & 0.14 ± 0.0, respectively). Similar improved potency of AmB-NLCs was also observed for other Leishmania and fungal strains compared with drug solution. Topical application of AmB-NLCs on L. major-infected BALB/c mice caused a significant reduction in parasite burden per mg of lesion (65 × 108 ± 13) compared with the control group (> 167.8 × 108 ± 11). Topical AmB-NLCs gel demonstrated superior efficacy in the vaginal C. albicans rat model for VVC as compared with plain AmB gel. Moreover, results of in vitro cytotoxicity assay and in vivo skin irritation test confirmed AmB-NLCs to be non-toxic and safe for topical use. In conclusion, NLCs may have promising potential as carrier for topical treatment of various conditions of skin and mucosa.


Assuntos
Anfotericina B/administração & dosagem , Candidíase Vulvovaginal/tratamento farmacológico , Leishmaniose Cutânea/tratamento farmacológico , Nanoestruturas/administração & dosagem , Administração Tópica , Animais , Candidíase Vulvovaginal/metabolismo , Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Géis/metabolismo , Humanos , Lipídeos/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Tamanho da Partícula , Ratos , Pele/metabolismo , Absorção Cutânea
12.
Toxicol Appl Pharmacol ; 401: 115091, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32525019

RESUMO

Prostate cancer (PCa) incidence is surging in United States and other parts of the world. Synthetic and natural compounds have been explored as potential modulators of PI3K/Akt signaling that is known to drive PCa growth. Here, we evaluated the efficacy of a series of triphenyltin (IV) carboxylate derivatives against PCa. From this library, triphenylstannyl 2-(benzylcarbamoyl)benzoate (Ch-319) resulted in reduced viability and induction of cell cycle arrest in PTEN-/- PC3M and PTEN+/- DU145 cells. In parallel, downregulation of PI3K p85/p110 subunits, dephosphorylation of Akt-1 and increase in FOXO3a expression were observed. In silico studies indicated binding interactions of Ch-319 within the ATP binding site of Akt-1 at Met281, Phe442 and Glu234 residues. Elevated po-pulation of apoptotic cells, activation of Bax and reduced Bcl2 expression indicated apoptosis by Ch-319. Pre-sensitization of PCa cells with Ch-319 augmented the effect of cabazitaxel, a commonly used taxane in patients with castration-resistant PCa. Next, in a prostate-specific PTENp-/- mice, Ch-319 showed reduced weights of genitourinary apparatus as compared to DMSO treated controls. Histological studies indicated absence of neoplastic foci in Ch-319 treated prostates. Consistently, dephosphorylation of Akt-1, reduced expression of PRAS40 and androgen receptor and increase in FOXO3a were observed in treated group. Notably, no overt organ toxicity was noted in Ch-319 treated animals. Our studies identify Akt/FOXO3a signaling as a target of triphenyltin (IV) carboxylate Ch-319 and provide a molecular basis of its growth inhibitory effect in PCa cells. We propose that Ch-319 has the potential to be developed as an anticancer agent against PCa.


Assuntos
Progressão da Doença , Proteína Forkhead Box O3/biossíntese , Compostos Orgânicos de Estanho/química , Compostos Orgânicos de Estanho/farmacologia , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Linhagem Celular Transformada , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Compostos Orgânicos de Estanho/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Distribuição Aleatória , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
13.
Infect Agent Cancer ; 15: 35, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32508980

RESUMO

Background: Hepatitis C virus (HCV) represents a major risk factor for hepatocellular carcinoma (HCC) development and anti-HCV therapy is a significant measure to reduce the incidence of HCC, however development of HCC in HCV treated patients is an emerging clinical problem which needs to be investigated. In this study we aim to analyze association between anti-HCV therapy and tumor pattern of HCV related HCC patients. Methods: Hepatocellular Carcinoma (HCC) patients with seropositivity for hepatitis C virus (HCV) antibodies, registered at three tertiary care hospitals of Rawalpindi and Islamabad, Pakistan during August 2017 to July 2018 were enrolled. Selected patients were then segregated in two groups on the basis of their HCV treatment history i.e., "TN" (HCV Treatment Naïve i.e. having no history/medical record for treatment prior to HCC diagnosis) and "TH" (Treated for HCV infection). Aggressiveness index (AgI) scoring system was applied to determine the tumor pattern. Univariate and multivariate analysis was carried out to analyze the independent effect of anti-HCV therapy on tumor pattern. Results: Out of 234 consecutive HCC patients, 171 HCV-related HCC patients were enrolled in final analysis and labeled as "TN" (n = 120) and "TH" (n = 51). Tumor pattern was found to be significantly aggressive (P = 0.02) in the treated cohort with an adjusted odds of 2.47 for aggressive and 6.92 for highly aggressive tumor. Neutrophil to lymphocyte ratio (NLR) was strongly associated with highly aggressive tumor pattern (P = 0.012). Patients in TN group were found to be marginally older than those in the TH group (59.5 vs. 55 years) where mean age of the patients treated with direct acting anti-viral agents was found to be visibly lower than mean age of patients who received interferon based treatment (53.5 vs. 57 years) with significant masculine predominance (62.1 vs. 37.9%, P = 0.049). Conclusion: We observed raised neutrophil to lymphocyte ratio and prominence of younger age with aggressive tumor biology in HCV treated HCC patients. These observations highlight the need for a longitudinal prospective study on HCV positive subjects treated with antivirals, irrespective of treatment response.

14.
Am J Trop Med Hyg ; 103(1): 221-230, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32372744

RESUMO

Globally, Pakistan ranks fifth in terms of missing tuberculosis (TB) patients' burden. Missed TB cases are either undiagnosed or diagnosed but not notified to the national TB database. Public-private mix interventions are contributing significantly to the case detection, diagnosis, and treatment of TB in Pakistan. However, it is estimated that many cases of infected TB patients go undetected. It is likely that these "undiagnosed" active TB cases seek treatment from community pharmacies, among other venues. This study aimed at assessing the feasibility of community pharmacy-based TB case detection. Case detection protocol implementation in three Pakistani districts in a nonrandom selection of pharmacies was followed by a review of routinely maintained prospective records of patients referred from these private community pharmacies to general practitioner (GP) clinics. The study engaged 500 community pharmacies for referring presumptive TB patients to GP clinics. In total, 85% of the engaged pharmacies remained active in providing referrals during the study period. The community pharmacy-referral network achieved an annual referral rate of 3,025 presumptive TB patients and identified 547 active TB cases for the period January-December 2017. Every fifth referral among presumptives presenting and counseled at pharmacies was diagnosed with TB at GP clinics. This contribution was 9% of all new TB cases identified in these districts through all other private venues linked with the Greenstar Social Marketing setup. Identified barriers and facilitators to implementation and cost effectiveness of pharmacy models for TB case detection should be considered if the model were to be scaled up.


Assuntos
Farmácias , Tuberculose Pulmonar/diagnóstico , Doenças não Diagnosticadas/diagnóstico , Adolescente , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Encaminhamento e Consulta , Tuberculose Pulmonar/epidemiologia , Doenças não Diagnosticadas/epidemiologia , Adulto Jovem
15.
Eur J Pharm Sci ; 145: 105256, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32032778

RESUMO

The present study evaluates the efficacy of sodium stibogluconate (SSG) co-loaded with ketoconazole (KTZ) in nano-elastic liposomes (NELs) for the topical treatment of cutaneous leishmaniasis (CL). SSG-KTZ co-loaded NELs were developed and assessed for various physicochemical properties and anti-leishmanial potential. The optimized nano-vesicles have an average size of 212.8 ± 3.1 nm and entrapment efficiency of 61.2 ± 2.9%. SSG-KTZ co-loaded NELs displayed 5.37-fold higher skin permeation of SSG as compared to drug solution. SSG and KTZ displayed a synergistic interaction and flow cytometry revealed enhanced killing of DsRed Leishmania mexicana in infected macrophages. In-vitro and in-vivo anti-leishmanial studies indicated a 10.67-fold lower IC50 value and a 35.33-fold reduced parasitic burden as compared with plain SSG solution, respectively. SSG-KTZ co-loaded NELs were found to be a promising approach for the topical treatment of CL.


Assuntos
Gluconato de Antimônio e Sódio/administração & dosagem , Antiprotozoários/administração & dosagem , Elasticidade , Cetoconazol/administração & dosagem , Leishmaniose Cutânea/tratamento farmacológico , Nanopartículas/administração & dosagem , Administração Tópica , Animais , Gluconato de Antimônio e Sódio/metabolismo , Antiprotozoários/metabolismo , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/metabolismo , Feminino , Cetoconazol/metabolismo , Leishmaniose Cutânea/metabolismo , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/metabolismo , Técnicas de Cultura de Órgãos , Distribuição Aleatória , Pele/efeitos dos fármacos , Pele/metabolismo
16.
Nanomedicine (Lond) ; 15(2): 183-203, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31916472

RESUMO

Aim: In this study, the targeting of rifampicin (RIF)-loaded nanotransfersomes (NTs) incorporated in chitosan gel for leishmania-infected macrophages via the topical route was investigated. Materials & methods: NTs were prepared through a thin-film hydration process and incorporated into chitosan gel. Results: The mean particle size of the NTs was 190 nm, with 83% encapsulation efficiency. The permeation rate of the NTs was threefold higher than that of the RIF solution. The NTs improved cellular internalization via passive targeting, which was confirmed by macrophage uptake evaluation. A low IC50 value, flow cytometry analysis and in vivo study demonstrated the RIF-loaded NTs enhanced apoptosis and had better antileishmanial effects. Conclusion: RIF-loaded NT gel could be a fitting carrier for the delivery of antileishmanial drugs in cutaneous leishmaniasis.


Assuntos
Quitosana/farmacologia , Leishmaniose Cutânea/tratamento farmacológico , Polietilenoglicóis/farmacologia , Polietilenoimina/farmacologia , Rifampina/farmacologia , Administração Tópica , Animais , Antiprotozoários/química , Antiprotozoários/farmacologia , Quitosana/química , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Citometria de Fluxo , Humanos , Leishmaniose Cutânea/parasitologia , Leishmaniose Cutânea/patologia , Macrófagos/efeitos dos fármacos , Camundongos , Nanogéis , Nanopartículas/química , Ratos , Rifampina/química
17.
J Microencapsul ; 37(2): 160-169, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31916886

RESUMO

The aim of this study was to develop levosulpiride-loaded solid lipid nanoparticles (SLNs) with enhanced solubilisation and bioavailability. The levosulpiride loaded-SLNs were composed of levosulpiride, stearic acid, and tween 80 in their respective weight ratios of (1, 5, and 1.5 mg) dissolved in 1 ml distilled water. Physicochemical properties of the SLNs such as particle size, shape, crystallinity, and chemical interaction were evaluated. Further, the in vitro drug dissolution, pharmacokinetic and stability studies of the SLNs were performed. The SLNs were rounded shaped stable nanoparticles with average diameter of 200 nm. They demonstrate 1.5- and 3-fold better drug dissolution when compared with the commercial product and levosulpiride powder, respectively. The SLNs enhanced the bioavailability of levosulpiride 3 times and 7 times, respectively, when compared with the commercial product and levosulpiride powder. It can be concluded that SLNs are capable to improve the dissolution and bioavailability of levosulpiride, even more than the commercial product.


Assuntos
Portadores de Fármacos , Lipídeos , Nanopartículas/química , Sulpirida/análogos & derivados , Animais , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacologia , Lipídeos/química , Lipídeos/farmacocinética , Lipídeos/farmacologia , Masculino , Ratos , Ratos Sprague-Dawley , Sulpirida/química , Sulpirida/farmacocinética , Sulpirida/farmacologia
18.
Int J Pharm ; 573: 118900, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31765786

RESUMO

The present study aims to optimize and evaluate amphotericin B (AmB) and miltefosine (MTF) co-loaded second generation ultra-deformable liposomes (SGUDLs) for the topical treatment of cutaneous leishmaniasis (CL). The development of an effective topical drug formulation against CL is desirable because of its non-invasive nature, which may potentially enhance the patient adherence and treatment accessibility. AmB-MTF co-loaded SGUDLs were prepared and characterized for size, entrapment efficiency (EE) and elasticity. The optimized formulation was then subjected to ex-vivo permeation studies in addition to cytotoxicity and anti-leishmanial assays. The co-loaded SGUDLs had an average size of 139.7 ± 1.7 nm and high EE of 77.8 ± 3.9% with respect to AmB. The ex-vivo permeation of co-loaded SGUDLs exhibited 6.15-fold higher permeation of AmB. A synergistic interaction was observed between AmB and MTF, and anti-leishmanial activity of co-loaded SGUDLs against amastigotes of Lesihmania mexicana indicated 8.62 and 6.12-fold lower IC50 values of AmB and MTF as compared to plain drug solutions, respectively. The results of the in-vivo study displayed a significant reduction in the parasitic burden in an infected BALB/c experimental model of CL. In conclusion, AmB-MTF co-loaded SGUDLs could be an effective topical treatment option against CL.


Assuntos
Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Leishmaniose Cutânea/tratamento farmacológico , Fosforilcolina/análogos & derivados , Administração Cutânea , Anfotericina B/farmacocinética , Animais , Antiprotozoários/farmacocinética , Modelos Animais de Doenças , Combinação de Medicamentos , Composição de Medicamentos/métodos , Elasticidade , Feminino , Humanos , Concentração Inibidora 50 , Leishmania/isolamento & purificação , Leishmaniose Cutânea/parasitologia , Lipossomos , Camundongos , Nanopartículas/química , Carga Parasitária , Tamanho da Partícula , Permeabilidade , Fosforilcolina/administração & dosagem , Fosforilcolina/farmacocinética , Pele/metabolismo , Pele/parasitologia
19.
Eur J Pharm Biopharm ; 147: 57-68, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31883906

RESUMO

Chronic wound infections have become a challenging problem due to escalating antibiotic resistance and lack of viable delivery approaches. Carvacrol (CAR) has been reported to be effective against multidrug resistant pathogens. In this study, CAR was formulated into a site-specific nanoparticle (NP) delivery system using poly(caprolactone) (PCL) to achieve a sustained antimicrobial effect at infection sites. These NPs were further incorporated into dissolving microneedles (MNs) to facilitate painless application and overcome the necrotic tissue barrier which hinders drug penetration into wound bed. The release study exhibited significantly higher release of CAR from PCL NPs in the presence of bacteria, highlighting its potential for on-demand delivery. Moreover, encapsulation of CAR in PCL NPs resulted in 2-4 fold increase in its antimicrobial activity. Dermatokinetic studies revealed that CAR-PCL NPs-MNs were able to enhance skin retention of CAR after 24 h (83.8 ± 5.15%), compared to free CAR-MNs (7.3 ± 2.04%). Importantly, this novel approach exhibited effective antimicrobial activity in an ex-vivo wound model. Hence, these findings have proven the concept that loading of CAR into this advanced MNs platform can lead to sustained antimicrobial effect at desired site and may provide a novel effective approach for treatment of infected wounds. However, further studies must be conducted to investigate in-vivo efficacy of the developed system in an appropriate infection model.


Assuntos
Cimenos/administração & dosagem , Sistemas de Liberação de Medicamentos , Nanopartículas , Infecção dos Ferimentos/tratamento farmacológico , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacologia , Doença Crônica , Cimenos/farmacologia , Liberação Controlada de Fármacos , Agulhas , Estudo de Prova de Conceito , Pele , Suínos
20.
Expert Opin Drug Deliv ; 17(1): 97-110, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31786952

RESUMO

Objective: To test the hypothesis that miltefosine (MTF)-polyphenol co-loaded second-generation nano-transfersomes (SGNTs) can be an effective approach for the topical treatment of cutaneous leishmaniasis (CL).Methods: The co-loaded SGNTs with various MTF-polyphenol combinations were developed, evaluated and compared for the entrapment efficiency, vesicle size, deformability index, ex-vivo permeation, cytotoxicity, and anti-leishmanial potential, using both in-vitro and in-vivo models.Results: The co-loaded SGNTs were spherical in shape, with an average size of 119 ± 1.5 nm and a high entrapment efficiency of 73.7 ± 3.7%. The ex-vivo study displayed a 3.2-fold higher permeation of MTF when entrapped in co-loaded SGNTs, whereas cytotoxicity potential of co-loaded SGNTs was 43.2% higher than the MTF solution. A synergistic interaction was observed between MTF and apigenin (APG) among all polyphenols and an 8.0-fold lower IC50 was found against amastigotes of DsRed Leishmania mexicana, compared with the plain MTF solution. Moreover, the in-vivo studies displayed a 9.5-fold reduced parasitic burden in the L. mexicana infected BALB/c mice treated with MTF-APG co-loaded SGNTs gel.Conclusions: The potential of MTF-APG co-loaded SGNTs topical formulation is established for the first time as an effective drug delivery strategy against CL.

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