Role of nutritional supplements in the management of tendinopathies: focus on combination of type 1 collagen, vitamin C and mucopolysaccharides

Tendinopathy is a common disease that is difficult to manage due to its recurrent nature. It is associated with increased healthcare costs and significantly impacts quality of life of patients. Also, according to recent studies patients with high cholesterol and diabetes are at a higher risk of developing tendinopathy. There has been rise in the incidence of tendinopathies due to increase in sport activities, life expectancy and some other factors (environment, diet and some drug therapies). Approximately 30% of visits for musculoskeletal pain in general practice are related to tendon injury. Non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids remain the mainstay of treatment. Despite the use of current therapies, there is need of a supportive therapy that can help in the healing process towards development of physiologically normal tendons. Nutraceuticals have been used as supportive therapy for management of tendinopathies. This review focuses on the management of tendinopathy with special attention on role of nutraceuticals such as type I collagen, mucopolysaccharides and vitamin C in the management of tendinopathy. Clinical data suggests that this combination (type I collagen, mucopolysaccharides and vitamin C) promotes the endogenous synthesis of collagen type I, avoiding the accumulation of collagen type III and aggrecan, thus interfering with the degeneration of tendon tissue. Based on the available clinical data, combination of type I collagen, mucopolysaccharides and vitamin C not only reduce the clinical symptoms but also improve structural evolution of different types of tendinopathies as well as plantar fascitis

Darbepoetin alfa: review in the management of anemia in patients with chronic kidney disease

Chronic kidney disease (CKD) is a significant clinical problem across the world including India. The SEEK (Screening and Early Evaluation of Kidney Disease) study from India reported the prevalence of CKD as 17.2%. Diabetic nephropathy, undetermined etiology, chronic glomerulonephritis and hypertensive nephrosclerosis are the common causes of CKD in India. Rising rates of diabetes and hypertension, late presentation of patients to nephrologists and limited number of nephrologists in India adds to the concerns related to management of CKD. Considering the pathophysiology of CKD, anemia is almost an inevitable complication in these patients. Untreated anemia significantly contributes to the morbidity and mortality associated with CKD. Early recognition, timely management with appropriate therapy helps to reduce the complications of anemia. Erythropoiesis-stimulating agents (ESAs) are one of the important measures for correction of anemia in CKD patients. Darbepoetin, an ESA is a valuable therapeutic option for the treatment of anemia in CKD patients and has played a vital role in enhancing anemia management. In this article we reviewed the efficacy and safety data along with key benefits and place of darbepoetin alfa in the management of anemia in CKD patients

Identification and characterization of 3-substituted pyrazolyl esters as alternate substrates for cathepsin B: The confounding effects of DTT and cysteine in biological assays

Substituted pyrazole esters were identified as hits in a high throughput screen (HTS) of the NIH Molecular Libraries Small Molecule Repository (MLSMR) to identify inhibitors of the enzyme cathepsin B. Members of this class, along with functional group analogs, were synthesized in an effort to define the structural requirements for activity. Analog characterization was hampered by the need to include a reducing agent such as dithiothreitol (DTT) or cysteine in the assay, highlighting the caution required in interpreting biological data gathered in the presence of such nucleophiles. Despite the confounding effects of DTT and cysteine, our studies demonstrate that the pyrazole 1 acts as alternate substrate for cathepsin B, rather than as an inhibitor

Statistička analiza nanokapsuliranja niskomolekularnog heparina

The objective of this study was to use Box-Behnken design (BBD) to investigate the influence of formulation variables on the properties of heparin-loaded poly(lactic-co-glycolic acid) (PLGA)-Eudragit-RLPO (E-RLPO) nanoparticles (NP) in terms of mean diameter (as size) and drug encapsulation efficiency. The NPs were prepared by the double emulsion solvent evaporation method. The independent variables were: X1 olymer mass ratio (PLGA:E-RLPO) in the oil phase, X2 concentration of polyvinyl alcohol (PVA) as emulsion stabilizer, and X3 volume of the external aqueous phase (W2). Particle size (analyzed by dynamic light scattering) and encapsulation efficiency (EE, estimated by spectrophotometry) were the investigated responses. The polynomial equation obtained from regression analysis of the reduced model (p = 0.0002, F = 25.7952 and R2 = 0.96) provided an excellent fit. The optimal size for the NP was found to be 134.2 ± 16.5 nm with formulation variables of 48.2:61.8, 0.321 (%, m/V) and 263 mL for X1, X2 and X3, respectively. Probably, due to electrostatic interaction between the negatively charged drug and the positively charged E-RLPO, the percent EE of heparin was between 74.4 ± 6.5 % (lowest value) and 92.1 ± 5.3 % (highest value). The data suggest that BBD is a useful tool in rational design of heparin-loaded NPs.Box-Behnkenovo dizajniranje (BBD) primijenjeno je za praćenje utjecaja formulacijskih varijabli na svojstva nanočestica (NP) s heparinom. Za izradu nanočestica korišten je kopolimer mliječne i glikolne kiseline (PLGA) i Eudragit-RLPO (E-RLPO). Nanočestice su pripravljene metodom dvostruke evaporacije otapala iz emulzije. Nezavisne varijable bile su: X1 omjer masa polimera (PLGA : E-RLPO) u uljnoj fazi, X2 koncentracija polivinil alkohola (PVA) kao stabilizatora emulzije i X3 volumen vanjske vodene faze (W2). Zavisne varijable bile su veličina čestica (analizirana pomoću dinamičkog rasapa svjetlosti) i učinkovitost inkapsuliranja (EE) (praćena spektrofotometrijski). Polinomska jednadžba dobivena regresijskom analizom reduciranog modela odlično je odgovarala (p = 0,0002, F = 25,7952 i R2 = 0,96). Optimalna veličina nanočestica bila je 134,2 ± 16,5 nm s formulacijskim varijablama 48,2:61,8, 0,321 (%, m/V) i 263 mL for X1, X2 odnosno X3. Vjerojatno je zbog elektrostatskih interakcija između negativno nabijene ljekovite tvari i pozitivno nabijenog E-RLPO učinkovitost inkapsuliranja heparina varirala od 74,4 ± 6,5 % (najniža vrijednost) do 92,1 ± 5,3 % (najviša vrijednost). Rezultati sugeriraju da je BBD vrlo korisno u racionalnom dizajniranju nanočestica s heparinom

Pulmonary Delivery of Proteins Using Nanocomposite Microcarriers.

In this study, Taguchi design was used to determine optimal parameters for the preparation of bovine serum albumin (BSA)-loaded nanoparticles (NPs) using a biodegradable polymer poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL). NPs were prepared, using BSA as a model protein, by the double emulsion evaporation process followed by spray-drying from leucine to form nanocomposite microparticles (NCMPs). The effect of various parameters on NP size and BSA loading were investigated and dendritic cell (DC) uptake and toxicity. NCMPs were examined for their morphology, yield, aerosolisation, in vitro release behaviour and BSA structure. NP size was mainly affected by the polymer mass used and a small particle size ≤500 nm was achieved. High BSA (43.67 ± 2.3 μg/mg) loading was influenced by BSA concentration. The spray-drying process produced NCMPs (50% yield) with a porous corrugated surface, aerodynamic diameter 1.46 ± 141 μm, fine particle dose 45.0 ± 4.7 μg and fine particle fraction 78.57 ± 0.1%, and a cumulative BSA release of 38.77 ± 3.0% after 48 h. The primary and secondary structures were maintained as shown by sodium dodecyl sulphate poly (acrylamide) gel electrophoresis and circular dichroism. Effective uptake of NPs was seen in DCs with >85% cell viability at 5 mg/mL concentration after 4 h. These results indicate the optimal process parameters for the preparation of protein-loaded PGA-co-PDL NCMPs suitable for inhalation. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci

Corrigendum

Corrected citationMotlekar N. Optimization of experimental parameters for the production of LMWH-loaded polymeric microspheres. Drug Des Devel Ther. 2008;2:39–47.Note Dr Bi-Botti Youan was incorrectly identified as a co-author in the original publication.Read the original articl