A nanoemulsion-based delivery system for imatinib and in vitro anticancer efficacy

A self-nanoemulsifying drug delivery system (SNEDDS) composed of ethyl oleate, Tween 80 and polyethylene glycol 600 was prepared as a new route to improve the efficacy of imatinib. The drug-loaded SNEDDS formed nanodroplets of ethyl oleate stabilized by Tween 80 and polyethylene glycol 600 with a diameter of 81.0±9.5 nm. The nanoemulsion-based delivery system was stable for at least two months, with entrapment efficiency and loading capacity of 16.4±0.1 and 48.3±0.2%, respectively. Imatinib-loaded SNEDDS was evaluated for the drug release profiles, and its effectiveness against MCF-7 cell line was investigated. IC50 values for the imatinib-loaded SNEDDS and an imatinib aqueous solution were 3.1 and 6.5 µg mL-1, respectively.

Preparation and evaluation of azithromycin binary solid dispersions using various polyethylene glycols for the improvement of the drug solubility and dissolution rate

ABSTRACT Azithromycin is a water-insoluble drug, with a very low bioavailability. In order to increase the solubility and dissolution rate, and consequently increase the bioavailability of poorly-soluble drugs (such as azithromycin), various techniques can be applied. One of such techniques is "solid dispersion". This technique is frequently used to improve the dissolution rate of poorly water-soluble compounds. Owing to its low solubility and dissolution rate, azithromycin does not have a suitable bioavailability. Therefore, the main purpose of this investigation was to increase the solubility and dissolution rate of azithromycin by preparing its solid dispersion, using different Polyethylene glycols (PEG). Preparations of solid dispersions and physical mixtures of azithromycin were made using PEG 4000, 6000, 8000, 12000 and 20000 in various ratios, based on the solvent evaporation method. From the studied drug release profile, it was discovered that the dissolution rate of the physical mixture, as the well as the solid dispersions, were higher than those of the drug alone. There was no chemical incompatibility between the drug and polymer from the observed Infrared (IR) spectra. Drug-polymer interactions were also investigated using Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Scanning Election Microscopy (SEM). In conclusion, the dissolution rate and solubility of azithromycin were found to improve significantly, using hydrophilic carriers, especially PEG 6000.

RESUMO A azitromicina é um fármaco insolúvel em água, com biodisponibilidade muito baixa. A fim de aumentar a taxa de solubilidade e dissolução e, consequentemente, aumentar a biodisponibilidade de fármacos fracamente solúveis (tais como azitromicina), várias técnicas podem ser aplicadas. Uma dessas técnicas é a "dispersão sólida", frequentemente usada para melhorar a taxa de dissolução de compostos fracamente solúveis em água. Devido à baixa taxa de solubilidade e de dissolução, este fármaco não tem biodisponibilidade adequada. Portanto, o principal objetivo desta pesquisa foi o de aumentar a taxa de solubilidade e dissolução da azitromicina, preparando a sua dispersão sólida, utilizando diferentes glicóis de polietileno (PEG). As dispersões sólidas e as misturas físicas de azitromicina foram preparadas utilizando PEG 4000, 6000, 8000, 12000 e 20000, em várias proporções, com base no método de evaporação do solvente. O perfil de liberação do fármaco foi estudado e verificou-se que tanto a taxa de dissolução da mistura física quanto as dispersões sólidas foram maiores do que as do fármaco sozinho. Espectros de IR não revelaram incompatibilidade química entre o fármaco e o polímero. Interações fármaco-polímero também foram investigadas usando calorimetria diferencial de varredura (DSC), Difração de Raios X (PXRD) e Microscopia Eletrônica de Varredura(SEM). Em conclusão, a taxa de dissolução e a solubilidade da azitromicina melhoraram, de forma significativa, utilizando suportes hidrofílicos, especialmente PEG 6000.

Effects of polyethylene glycols on intestinal efflux pump expression and activity in Caco-2 cells

The present study was planned to investigate the influence of polyethylene glycols (PEGs) on the activity and expression of P-glycoprotein (P-gp). Sub-toxic concentrations of PEGs in Caco-2 cells were determined using the MTT test assay. Then the measurement of Rhodamine-123 (Rho-123) uptake, a P-gp fluorescence substrate, in Caco-2 cells confronting PEG 400 (1% and 2% w/v), PEG 4000 (2% and 4% w/v), PEG 6000 (2% and 4% w/v), PEG 10000 (2% and 4% w/v), PEG 15000 (1% and 2% w/v), and PEG 35000 (2% and 4% w/v) overnight was taken to elucidate whether non-toxic concentrations of PEGs are able to impact P-gp activity. Furthermore, western blotting was carried out to investigate P-gp protein expression. The results showed that PEG 400 at concentrations of 1% (w/v) and 2% (w/v) and PEG 6000 at the concentration of 4% (w/v) are notably capable of blocking P-gp. Based on the obtained results it is concluded that the mentioned excipients could be used to obstruct P-gp efflux transporter in order to increase the bioavailability of co-administered substrate drug.

O presente estudo foi planejado para investigar a influência de polietileno glicóis sobre a atividade e expressão da P- glicoproteína (P-gp) . Concentrações sub-tóxicas de PGPs e em células Caco-2 foram determinadas por meio do ensaio de MTT. Em seguida, efetuou-se a a medida de captura de Rodamina-123 (Rho-123), um substrato fluorescente de P-gp, em células Caco-2, confrontando com PEG 400 (1% e 2% m/v), PEG 4000 (2% e 4% m/v) e PEG 6000 (2% e 4% m /v), PEG 10000 (2% e 4% w/v), PEG 15000 (1% e 2% m/v), e PEG 35000 (2% e 4% m/v). Essa medida foi efetuada durante a noite, para saber se as concentrações não tóxicas de excipientes são capazes de influenciar a actividade da P-gp. Além disso, realizou-se o western blotting para investigar a expressão da proteína P-gp. Os resultados mostraram que o PEG 400, nas concentrações de 1% (m/v) e 2% (m/v), e PEG 6000, na concentração de 4% (m/v) são capazes de bloquear P-gp. Com base nos resultados conclui-se que os excipientes mencionados poderiam ser utilizados para obstruir o efluxo por P-gp, a fim de aumentar a biodisponibilidade de do fármaco co-administrado.

The influence of pH, polyethylene glycol and polyacrylic acid on the stability of stem bromelain

Enzyme stability is critical in biotechnology, pharmaceutical and cosmetic industries. Investigations on this subject have drawn attention because of its practical application. Bromelain is a thiol-endopeptidase, obtained from pineapple (Ananas comosus), known for its clinical and therapeutic applications, particularly to selective burn debridement and improvement of antibiotic action and anti-inflammatory activities. To date, the use of bromelain in pharmacological or industrial applications is limited, due to commercial availability, costs, and sensitivity to pH and temperature. Therefore, a better understanding of enzyme stability would be of great interest. The aim of this study was to evaluate bromelain activity and stability in several pH (2.0 to 8.0) and in polyethylene glycol and polyacrylic acid solutions. We observed that bromelain was able to maintain its stability at pH 5.0 for the temperatures studied. PEG solutions increased bromelain stability, but PAA solutions had the opposite effect.

Estabilidade de enzimas é uma questão fundamental em indústrias biotecnológicas, farmacêuticas e cosméticas. As investigações sobre o assunto têm chamado a atenção por sua aplicação prática. A bromelina é uma tiol-endopeptidase, obtida a partir do abacaxi (Ananas comosus). É conhecida por suas aplicações clínicas e terapêuticas, especialmente para desbridamento seletivo de queimaduras, melhoria de ações antibiótica e de atividades anti-inflamatórias. Até o momento, a utilização da bromelina em aplicações farmacológicas industriais é limitada, devido à disponibilidade comercial, os custos, a sensibilidade ao pH e temperatura. Portanto, a maior compreensão da estabilidade desta enzima seria de grande interesse. O objetivo deste estudo foi avaliar a estabilidade da atividade da bromelina em vários pH (2,0 a 8,0) e em soluções de polietilenoglicol e de ácido poliacrílico. Observamos que a bromelina foi capaz de manter a sua estabilidade em pH 5.0, em todas as temperaturas estudadas. Soluções de PEG aumentaram a estabilidade da bromelina, enquanto que soluções de PAA obtiveram efeito oposto.

Study of Fluconazole Release from O/W Cream and Water Soluble Ointment Bases.

Aims: Study the release of fluconazole from different O/W creams and PEG ointments. Study Design: In this study, different formulations were prepared with changing one of the added excipients and study the effect of this change on the drug release and then the selected formulations were subjected to antifungal activity study. Place and Duration of Study: Faculty of Pharmacy, Department of Pharmaceutics, Assiut University, Assiut, Egypt, between December 2011 and March 2012. Methodology: O/W creams were prepared with changing either fatty alcohol type or the concentration of the added emulsifying agent. Also, the PEG ointments were prepared with changing the type of the liquid PEG (low molecular weight). Then, the viscosity and the fluconazole release from the prepared formulations were studied. Results: Changing the fatty alcohol type from stearyl to cetostearyl and cetyl alcohol in the O/W creams caused an increase in the viscosity and a decrease in the drug release. Also, changing the liquid PEG from PEG 400 to PEG 600 resulted in an increase in the formulation viscosity and subsequent decrease in the drug release. Both F1 and F6 showed a good inhibition to the fungal growth against Candida albicans and Trichophyton mentagrophyte using cup plate method, also PEG base showed a slight fungal growth inhibition. Conclusion: Results obtained showed that the PEG ointment formulations exhibited higher fluconazole release after three hours over the O/W cream formulations. Also, the nature of the PEG base may be adjunctive to the efficacy of the antifungal agent.

Efeitos laxativos do polietilenoglicol 3350 e de soluções eletrolíticas em equinos / Laxative effects of polyethylene glycol 3350 and electrolyte solutions in equines

Compararam-se a motilidade intestinal, a frequência de defecação, a umidade e o aspecto das fezes, o tempo médio de retenção (TMR) e a taxa de passagem (TxP) da ingesta no intestino grosso (ig), em cinco éguas hígidas tratadas com: polietilenoglicol 3350, na dose única de 1,5g kg-1, em bolus, por via enteral (PEG); ou por polietilenoglicol 3350, na dose única de 1,5g kg-1, em bolus, por via enteral, associado ao Ringer lactato, 15mL kg-1 h-1 por fluxo contínuo de 12h, via intravenosa (PEG+RL); ou por solução isotônica poliônica enteral, 15mL kg-1 h-1 em fluxo contínuo de 12h (SIPE); ou por solução isotônica poliônica enteral, 7,5mL kg-1 h-1 por fluxo contínuo de 12h, via enteral, associada ao Ringer lactato, 7,5mL kg-1 h-1 por fluxo contínuo de 12h, via intravenosa (SIPE+RL); ou por cloreto de sódio 0,9%, 15mL kg-1 h-1 por fluxo contínuo de 12h, via intravenosa (NaCl 0,9%). O PEG apenas amoleceu discretamente as fezes. O PEG+RL, o SIPE+RL e o NaCl 0,9% foram mais eficazes em amolecer as fezes e aumentar a frequência de defecação do que o PEG. O SIPE foi o único tratamento que aumentou a motilidade intestinal, e foi o melhor em aumentar a frequência de defecações, amolecer as fezes e diminuir o TMRig, aumentando a TxPig. Conclui-se que os cinco tratamentos demonstraram efeito laxativo, sendo o SIPE o mais eficaz.

The intestinal motility, frequency of defecation, moisture and appearance of feces, mean retention time (MRT) and passage rate (RP) of ingesta in the large intestine (li) were compared in five healthy mares treated with: polyethylene glycol 3350 in a single dose of 1.5g kg-1, in bolus, administered enterally (PEG); or for polyethylene glycol 3350 in a single dose of 1.5g kg-1, in bolus, enterally, associated to the Ringer lactate, 15ml kg-1 h-1 by continuous flow of 12 hours, intravenously (PEG+RL); or for enteral isotonic polionic solution, 15ml kg-1 h-1 by continuous flow of 12 hours, enterally (SIPE); or for enteral isotonic polionic solution, 7,5ml kg-1 h-1 by continuous flow of 12 hours, enterally, associated to the Ringer lactate, 7.5mL kg-1 h-1 by continuous flow of 12 hours, intravenously (SIPE+RL); or sodium chloride 0.9 %, 15ml kg-1 h-1 by continuous flow of 12 hours, intravenously (NaCl 0.9%). PEG treatment only slightly softened feces. PEG+RL, SIPE+RL and NaCl 0.9% were more effective in softening the feces and increasing the frequency of defecation than PEG. SIPE was the best to increase the frequency of defecation, to soften the feces, and reduce the TMRli, increasing RPli. It is concluded that the five treatments demonstrated a laxative effect, but SIPE was the most effective.