RESUMO
The aim of present research work was to design, fabricate, optimize, and evaluate allopurinol (ALLO)-loaded bovine serum albumin nanoparticles (ABNPs) for kidney targeting of the drug and exploring the potential of fabricated ABNPs for management of hyperuricemia-related nephrolithiasis. ABNP formulation was prepared by employing desolvation technique, and its optimization was conducted by 2-factor-3-level central composite design (CCD) in order to achieve minimum particle size (PSA) and polydispersity index (PDI), maximum entrapment efficiency (EE), and zeta potential (ZP). Further, the optimized formulation (ABNPsopt) was also assessed for in vitro drug release study, TEM, DSC, XRD analysis, FTIR spectroscopy, and in vivo animal study. The in vivo study revealed that after 2 h of ABNPsopt administration, a significant concentration of ALLO was present in kidney (21.26-fold) as compared with serum while in case of standard pure drug group; no drug was seen in mice kidney and serum post 2 h administration, which indicates successful targeting of ALLO by formulating its albumin nanoparticles. Also, uric acid and pH levels were measured in serum and urine samples of mice which showed significant (P < 0.01) efficacy of ABNPsopt formulation in management of hyperuricemia-related nephrolithiasis. Histological studies on kidney samples also confirmed these outcomes. Findings of present study indicate higher kidney uptake of allopurinol from formulated ABNPsopt, which could be due to the specificity of albumin polymer for cubilin and megalin receptors, and it also serves as effective strategy in management of hyperuricemic-related nephrolithiasis.
Assuntos
Alopurinol/administração & dosagem , Supressores da Gota/administração & dosagem , Hiperuricemia/tratamento farmacológico , Nefrolitíase/tratamento farmacológico , Soroalbumina Bovina/química , Alopurinol/uso terapêutico , Animais , Portadores de Fármacos/química , Composição de Medicamentos , Supressores da Gota/uso terapêutico , Humanos , Hiperuricemia/complicações , Rim , Camundongos , Nanopartículas/química , Nefrolitíase/complicações , Tamanho da PartículaRESUMO
PURPOSE: The major short coming of conventional therapy system is that they can't deliver the therapeutics specifically to a site within the body without producing nonspecific toxicity. Present research aimed at developing kidney targeted allopurinol (AP) loaded chitosan coated magnetic nanoparticles (A-MNPs) for the management of hyperuricemic nephropathy manifested in the form of nephrolithiasis. METHODS: The work includes preparation of magnetic nanoparticles by chemical co-precipitation method and evaluation of the prepared batches for particle size analysis, Transmission electron microscopy, entrapment efficiency, in-vitro release study etc. Further, FTIR spectroscopy, X-ray diffraction, Differential Scanning Calorimetry, Vibrational sample magnetometer (VSM) and in-vivo animal studies were also performed. RESULTS: VSM analysis demonstrates that the prepared nanoparticles exhibit superparamagnetic magnetic behaviour which was retained even after coating by chitosan. In-vivo studies of A-MNPs showed 19.07-fold increase in kidney uptake of AP as compared to serum post 2 h of administration in mice whereas no drug was detected in kidney and serum post 2 h administration of pure drug (free-form) indicating successful targeting to kidney as well as sustained release of AP from the formulated A-MNPs. The significant (p < 0.01) effectiveness of A-MNPs in management of hyperuricemic nephrolithiasis was observed through estimating pH and uric acid levels in urine and serum samples of mice. These findings were also confirmed by histological examination of isolated kidney samples. CONCLUSION: Present investigation signifies that a simple external magnetic field is enough for targeting allopurinol to kidneys by formulating A-MNPs which further offers an effective approach for management of hyperuricemic nephrolithiasis. Graphical Abstract.
Assuntos
Alopurinol/administração & dosagem , Quitosana/química , Rim/química , Nefrolitíase/tratamento farmacológico , Administração Oral , Alopurinol/química , Alopurinol/farmacocinética , Animais , Precipitação Química , Modelos Animais de Doenças , Sistemas de Liberação de Medicamentos , Nanopartículas de Magnetita , Camundongos , Nanopartículas , Nefrolitíase/sangue , Nefrolitíase/induzido quimicamente , Nefrolitíase/urina , Ácido Oxônico/efeitos adversos , Ácido Úrico/sangue , Ácido Úrico/urinaRESUMO
BACKGROUND: Candidiasis is one of the most common opportunistic fungal infections caused by genus Candida. The genus is composed of around 200 species. The most virulent among all are, Candida albicans followed by various nonalbicans species. Despite various treatments available, the incidence of severe systemic fungal infections is increasing, and with it the related morbidity and mortality, in relation to the misuse of antimicrobials and the emergence of drug-resistant fungal species. Therefore, various novel therapeutic approaches need to be developed and explored to overcome these limitations and effective management of candidiasis. OBJECTIVE: In this review, we focused on natural herbal remedies and significance of novel formulation approaches for the treatment of candidiasis. CONCLUSION: The reported studies suggested the promising role of phytomedicines and novel polymeric drug delivery systems in therapeutic management of candidiasis. Phytomedicines are effective substitutes of synthetic drugs as they are inexpensive with lesser number of side effects. Various novel particulate approaches can be successfully used to reduce fungal burden at the target site.
Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candidíase/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Polímeros/farmacologia , Animais , Humanos , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: The liver is the largest and vital organ present in all vertebrates. It performs various major functions such as detoxification, metabolism, protein synthesis, excretion and so on. Liver cells are divided into parenchymal cells and non-parenchymal cells. Hepatocytes, Kupffer cells, hepatic stellate cells and sinusoidal endothelial cells, etc. are found in liver having different receptors present on their surface which can be used for liver targeting by binding to different ligands. OBJECTIVE: In this review, we focused on various factors such as drugs, plants; metals and so on are reported in literature to be responsible for causing hepatotoxicity, natural hepatoprotective agents and liver targeting via novel formulation approaches. CONCLUSION: All over the world, millions of people are affected by serious liver disorders which are very difficult to treat despite of many efforts. Hepatotoxicity is one of the major reasons due to which drugs continue to be taken off from the market. This review highlights the potential of various phytochemicals as hepatoprotective agents and various strategies which have been proposed to achieve liver targeting, including passive accumulation of therapeutic drug delivery system and active targeting by surface modifications of particulate formulation with specific ligands.
Assuntos
Hepatopatias/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Humanos , Hepatopatias/metabolismo , Nanopartículas Metálicas , Metais/toxicidade , Compostos Fitoquímicos/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
In the present study polyelectrolyte complex between carboxymethyl gum katira and chitosan were prepared and evaluated for drug delivery using ofloxacin as model drug. The carboxymethyl gum katira-chitosan polyelectrolyte complex was characterized by FTIR, DSC, TGA, DTG, XRD and SEM. The influence of concentration of CMGK/CH and drug loading (%) on yield (%) and drug entrapment (%) was studied using response surface methodology. The result of the study revealed that increasing the relative proportion of CMGK/CH in carboxymethyl gum katira-chitosan polyelectrolyte complex decreases the % yield and increases the % drug entrapment. The optimal calculated parameters were polymer ratio (CMGK/CH) 2.13 and drug loading 50 (%w/w). The optimized batch of carboxymethyl gum katira-chitosan polyelectrolyte complex had yield of 69.04%, entrapment efficiency of ofloxacin 84.86%. Further, the optimized batch of carboxymethyl gum katira-chitosan polyelectrolyte complex releases ofloxacin 84.32% following Higuchi's square-root kinetics.
Assuntos
Quitosana/análogos & derivados , Quitosana/química , Nanopartículas/química , Polieletrólitos/química , Quitosana/farmacologia , Sistemas de Liberação de Medicamentos , Goma Arábica/química , Goma Arábica/farmacologia , Humanos , Nanopartículas/ultraestrutura , Ofloxacino/química , Ofloxacino/farmacologia , Polieletrólitos/farmacologiaRESUMO
BACKGROUND: The effective targeted drug delivery system is significant for future development of medicinal product and healthcare. There are also different types of nanostructures which include solid lipid nanoparticles, liposomes, dendrimers, nanostructured lipid carriers, lipid drug conjugate, liquid crystalline particles, polymeric nanocrystals, polymeric nanoparticles and superparamagnetic nanoparticles which have been considered as advanced carriers in drug delivery system. Method & Discussion: In this regard, nano carriers are bringing revolution in therapeutic delivery of drug as compared to conventional delivery systems by overcoming the limitations of usual methods. CONCLUSION: The objective of this review is to cover the drug delivery system of various therapeutic drugs and biomolecules by means of polymeric nanoparticles, dendrimers, liposomal nanoparticles and magnetic nanoparticles by describing the methods of formulation development.
Assuntos
Portadores de Fármacos/química , Nanopartículas/química , Química Farmacêutica/métodos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Dendrímeros/química , Humanos , Lipídeos/química , Lipossomos/química , Polímeros/químicaRESUMO
PIP: Northeastern India is comprised of Assam, Arunachal Pradesh, Manipur, Meghalaya, Mizoram, Nagaland, and Tripura states. The Northeast is geographically diverse, mainly hilly, and with a rapidly changing topography. 100 tribal, ethnic, and linguistic groups who speak 449 different languages and dialects live in the region. 75% and 8% of the region's population lives in Assam and Tripura, respectively. Covering 7.8% of India's land area and 3.7% of its total population, Northeastern India has international borders with Tibet, Bhutan, Myanmar, and Bangladesh. The highly porous nature of the border with Bangladesh has adversely affected development in all sectors of the region. The widespread rural health infrastructure which exists in the Northeast needs to be improved.^ieng