Enhanced solubility and stability of PEGylated liposomal paclitaxel: in vitro and in vivo evaluation (original) (raw)
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Asian Journal of Pharmaceutical Sciences, 2011
The aim of the study was to investigate and characterize conventional (CL) and PEGylated liposomes (PL) of paclitaxel (PCL) prepared using hydrogenated soya phospatidylcholine (HSPC) and HSPC-distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000 (DSPE-PEG2000). The liposomes were prepared using thin film hydration method. The liposomes were optimized for their formulation parameters such as characterized for its formulation parameters such as drug; lipid ratios and cholesterol content, particle size analysis, percent entrapment, zeta potential, short term stability, morphology and size, In vitro release and anti-proliferative activity. The optimized conventional liposomes provided high percent entrapment efficiency (80.24%) and mean particle size of 211 nm at drug: lipid ratio of 1:25 and HSPC:cholesterol ratio of 8.5:1.5. The electroflocculation method showed 6 mol% of DSPE-PEG2000 was required to obtain maximum stability for PEGylated liposome. Both CL and PL liposomal formulations revealed uniform sized SUVs (nm) in the transmission electron microscopy (TEM) studies. Both the liposomal formulations showed a tendency to follow Higuchi diffusion pattern in pH 7.4 PBS containing 3% (v/v) Tween 80. The Chemosensitivity assay carried out in B16F10 cell lines showed that both the liposomal formulations had equipotent cytotoxicity as that of PCL solution after 48 hrs of incubation. PCL loaded conventional as well as PEGylated liposomes can be considered a promising system for in vivo PCL delivery.
International Journal of Applied Pharmaceutics, 2023
Objective: Liposomes are the controlled-release dosage form that improves the therapeutic efficacy of the drugs, prolongs the duration of action, reduces dosage frequency, and improves patient compliance. Methods: The thin-film hydration method was used to prepare Paclitaxel liposomes. In this process, cholesterol and sodium deoxycholate were used for the formulation, while chloroform and methanol were used as diluents. Percentage (%) drug release study was carried out in phosphate buffer at pH 7.4 in USP apparatus II (Paddle type)Model no VDA-8D, Veego, Mumbai, India. Results: Paclitaxel liposomes of various batches showed a percentage yield ranging from 38 to 84%. It was observed that (Encapsulation efficiency)EE% of Batches B1 to B10 were 0
A Strategic Process Development and in Vitro Cytotoxicity Analysis of Paclitaxel-Loaded Liposomes
International Journal of Applied Pharmaceutics
Objective: Liposomes are the controlled-release dosage form that improves the therapeutic efficacy of the drugs, prolongs the duration of action, reduces dosage frequency, and improves patient compliance. Methods: The thin-film hydration method was used to prepare Paclitaxel liposomes. In this process, cholesterol and sodium deoxycholate were used for the formulation, while chloroform and methanol were used as diluents. Percentage (%) drug release study was carried out in phosphate buffer at pH 7.4 in USP apparatus II (Paddle type)Model no VDA-8D, Veego, Mumbai, India. Results: Paclitaxel liposomes of various batches showed a percentage yield ranging from 38 to 84%. It was observed that (Encapsulation efficiency)EE% of Batches B1 to B10 were 0,62.33,59.51,50.21,44.30,82.25,88.95,72.34,77.37 and 70.63 percentage, respectively. Data fitting to the Peppas, Higuchi, 1st-order, and zero-order models was used to examine the optimized liposome (B7) release kinetic mechanism. Data compariso...
INFLUENCE OF LIPOSOME COMPOSITION ON PACLITAXEL ENTRAPMENT AND pH SENSITIVITY OF LIPOSOMES
2015
Abstract: The objective of the present investigation was to study the effect of composition of phospholipids on drug entrapment efficiency and pH sensitivity. In the present study, paclitaxel containing liposomes of different phospholipid compositions were formulated and compared. The formulation composed of Phospholipon 90G/DOPE/CHEMS 8:2:2(D) containing paclitaxel and lipids in the molar ratio of 1:30 (drug: lipid) was found to have good incorporation efficiency(94%). The highest paclitaxel concentration achievable in the liposomal formulation was 1.5 mg/ml. Liposomes with phospholipon 90 G alone couldn’t show pH sensitivity. Formulation B (Phospholipon 90G /DOPE 8:2) released drug at pH 5.5, but was unstable at pH 7.5. On inclusion of CHEMS, liposomes were stabilized at physiological pH, and released paclitaxel at lower pH. Thus including CHEMS into liposomal formulation of paclitaxel, composed of Phospholipon 90 G/DOPE has proved to be the most efficient pH sensitive system with...
PLoS ONE
Although the encapsulation of paclitaxel into liposomes has been extensively studied, its significant hydrophobic and uncharged character has generated substantial difficulties concerning its efficient encapsulation into the inner water core of liposomes. We found that a more hydrophilic paclitaxel molecule, 7-glucosyloxyacetylpaclitaxel, retained tubulin polymerization stabilization activity. The hydrophilic nature of 7-glucosyloxyacetylpaclitaxel allowed its efficient encapsulation into the inner water core of liposomes, which was successfully accomplished using a remote loading method with a solubility gradient between 40% ethylene glycol and Cremophor EL/ethanol in PBS. Trastuzumab was then conjugated onto the surface of liposomes as immunoliposomes to selectively target human epidermal growth factor receptor-2 (HER2)-overexpressing cancer cells. In vitro cytotoxicity assays revealed that the immunoliposomes enhanced the toxicity of 7-glucosyloxyacetylpaclitaxel in HER2-overexpr...
Colloids and Surfaces B: Biointerfaces, 2016
Paclitaxel and rapamycin have been reported to act synergistically to treat breast cancer. Albeit paclitaxel is available for breast cancer treatment, the most commonly used formulation in the clinic presents side effects, limiting its use. Furthermore, both drugs present pharmacokinetics drawbacks limiting their in vivo efficacy and clinic combination. As an alternative, drug delivery systems, particularly liposomes, emerge as an option for drug combination, able to simultaneously deliver co-loaded drugs with improved therapeutic index. Therefore, the purpose of this study is to develop and characterize a co-loaded paclitaxel and rapamycin liposome and evaluate it for breast cancer efficacy both in vitro and in vivo. Results showed that a SPC/Chol/DSPE-PEG (2000) liposome was able to co-encapsulate paclitaxel and rapamycin with suitable encapsulation efficiency values, nanometric particle size, low polydispersity and neutral zeta potential. Taken together, FTIR and thermal analysis evidenced drug conversion to the more bioavailable molecular and amorphous forms, respectively, for paclitaxel and rapamycin. The pegylated liposome exhibited excellent colloidal stability and was able to retain drugs encapsulated, which were released in a slow and sustained fashion. Liposomes were more cytotoxic to 4T1 breast cancer cell line than the free drugs and drugs acted synergistically, particularly when co-loaded. Finally, in vivo therapeutic evaluation carried out in 4T1-tumor-bearing mice confirmed the in vitro results. The co-loaded paclitaxel/rapamycin pegylated liposome better controlled tumor growth compared to the solution. Therefore, we expect that the formulation developed herein might be a contribution for future studies focusing on the clinical combination of paclitaxel and rapamycin.
Studies in Medical Sciences
Background & Aims: Owing to its anti-cancer and anti-oxidant properties, Kaempferol (KAE) has become an ideal candidate to be more welcome into clinical practice. However, Due to its low water solubility and bioavailability, we aimed to design and address a new liposomal formulation with KAE and evaluate its anti-cancer activity against MDA-MB 468 breast cancer cells. Materials & Methods: To characterize the physicochemical features, pharmaceutical parameters such as nanoparticle size, morphology of particles under scanning electron microscopy (SEM), and zeta potential were measured. The optimum liposomal formulation along with paclitaxel was incubated to investigate their biological activity against breast cancer cells. Furthermore, molecular mechanisms related to program cell death (apoptosis) and their gene expression were measured by flowcytometric and real-time PCR, respectively. Results: SEM images showed narrow distributed and scattered particles with the size of 80.3 nm (KAE) formulated in liposomes. IC50 values for KAE and paclitaxel were determined to be as 44 ± 0.52 μM and 1.75 ± 0.36 nM, respectively. Cell proliferation averaged from 44 ± 3.9% to 56 ± 26.8% (p <0.05) after treatment with KAE-loaded liposomes. Co-administration of nanoparticles containing KAE and paclitaxel in cancer cells significantly increased the percentage of apoptosis (P <0.05). Conclusion: Taking our data into consideration, we suggest that insertion of KAE into liposomal carriers not only improved the bioavailability of this flavonoid but also surged the anti-cancer efficacy of paclitaxel.
European Journal of Pharmaceutics and Biopharmaceutics, 2005
Taxol w is a marketed product for the treatment of ovarian, breast, non-small cell lung cancer and AIDS-related Kaposi's Sarcoma. It is thus far one of the most effective anticancer drugs available on the market. However, paclitaxel is only sparingly soluble in water and therefore, intravenous administration depends on the use of the non-ionic surfactant Cremophor w EL (polyethoxylated castor oil) to achieve a clinically relevant concentrated solution. Unfortunately, Cremophor w EL increases toxicity and leads to hypersensitivity reactions in certain individuals. We have developed a well characterized novel lyophilized liposome-based paclitaxel (LEP-ETU) formulation that is sterile, stable and easy-to-use. The mean particle size of the liposomes is about 150 nm before and after lyophilization, and the drug entrapment efficiency is greater than 90%. Stability data indicated that the lyophilized LEP-ETU was physically and chemically stable for at least 12 months at 2-8 and 25 8C. Moreover, the formulation can be diluted to about 0.25 mg/ml without drug precipitation or change in particle size. In vitro drug release study in phosphate-buffered saline (PBS, pH 7.4) showed that less than 6% of the entrapped paclitaxel was released after 120 h, indicating that the drug is highly stable in an entrapped form at physiologic temperature. q
Archives of Pharmacal Research, 2011
A mixed polymeric micelle formulation of paclitaxel (PTX) has been developed with the purpose of improving the solubility and prolonging the time of blood circulation of PTX in comparison to current Taxol injection. The mixed micelles were prepared by thin-ˆlm method using a nonionic surfactant Pluronic P105, L101 and PTX. The mean size of PTX-loaded mixed micelles was 185 nm with narrow size distribution shown by a dynamic light scattering sizer and a transmission electron microscopy. The in vitro release proˆles indicated that PTX release from the mixed micelles exhibited a sustained release behavior. A similar phenomenon was also observed in a pharmacokinetic assessment in rats, in which t 1/2b and AUC of the mixed micelle formulation were 5.5 and 4.9-fold higher than that of Taxol injection. The biodistribution study in mice showed that the PTX-loaded mixed micelles not only decreased drug uptake by liver, but also prolonged drug retention in blood, and increased distribution of the drug in lung, spleen and kidney. These results suggested that the mixed polymeric micelles may e‹ciently load, protect and retain PTX in both in vitro and in vivo environments, and could be a useful drug carrier for intravenous administration of PTX.