5 research outputs found
Successful co-encapsulation of benzoyl peroxide and chloramphenicol in liposomes by a novel manufacturing method - dual asymmetric centrifugation
Accepted manuscript version. Published version available at http://dx.doi.org/10.1016/j.ejps.2016.11.017 Encapsulation of more than one active pharmaceutical ingredient into nanocarriers such
as
liposomes is an attractive approach to achieve a synergic drug effect and less complicated dosing
schedules in multi-drug treatment regimes. Liposomal drug delivery in acne treatment may improve
drug efficiency by targeted delivery to pilosebaceous units, reduce adverse effects and improve
patient compliance. We therefore aimed to co-encapsulate benzoyl peroxide (BPO) and chloramphenicol
(CAM) into liposomes using the novel liposome processing method – dual asymmetric centrifugation
(DAC). Liposomes were formed from soybean lecithin, propylene glycol and distilled water (2:1:2
w/v/v ratio), forming a viscous liposome dispersion. Liposomes containing both drugs (BPO-CAM-Lip),
single-drug (BPO-Lip and CAM-Lip), and empty liposomes were prepared. Drug entrapment of BPO and
CAM was determined by a newly developed HPLC method for simultaneous detection and quantification
of both drugs. Encapsulation of around 50% for BPO and 60% for CAM respectively was obtained in
both single- drug encapsulated formulations (BPO-Lip and CAM-Lip) and co-encapsulated formulations
(BPO- CAM-Lip). Liposome sizes were comparable for all liposome formulations, ranging from 130 to
150 nm mean diameter, with a polydispersity index < 0.2 for all formulations. CAM exhibited a
sustained release from all liposomal formulations, whereas BPO appeared retained within the
liposomes. BPO retention could be attributed to its poor solubility. However, HaCaT cell toxicity
was found dependent on BPO released from the liposomes. In the higher concentration range (4% v/v),
liposomal formulations were less cytotoxic than the corresponding drug solutions used as reference.
We have demonstrated that DAC is a fast, easy, suitable method for encapsulation of
more than one drug within the same liposomes
Cleavage of the urokinase receptor (uPAR) on oral cancer cells: Regulation by transforming growth factor - beta1 (TGF-beta1) and potential effects on migration and invasion
Source at https://doi.org/10.1186/s12885-017-3349-7 Background: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion. The aim of the current study was to analyse tumour associated factors and their effect on uPAR cleavage, and the potential implications for cell proliferation, migration and invasion. Methods: Mouse uPAR was stably overexpressed in the mouse OSCC cell line AT84. The ratio of full-length versus cleaved uPAR as analysed by Western blotting and its regulation was assessed by addition of different protease inhibitors and transforming growth factor - β 1(TGF- β 1). The role of uPAR cleavage in cell proliferation and migration was analysed using real-time cell analysis and invasion was assessed using the myoma invasion model. Results: We found that when uPAR was overexpressed a proportion of the receptor was cleaved, thus the cells presented both full-length uPAR and uPAR (II-III). Cleavage was mainly performed by serine proteases and urokinase plasminogen activator (uPA) in particular. When the OSCC cells were stimulated with TGF- β 1, the production of the uPA inhibitor PAI-1 was increased, resulting in a reduction of uPAR cleavage. By inhibiting cleavage of uPAR, cell migration was reduced, and by inhibiting uPA activity, invasion was reduced. We could also show that medium containing soluble uPAR (suPAR), and cleaved soluble uPAR (suPAR (II-III)), induced migration in OSCC cells with low endogenous levels of uPAR. Conclusions: These results show that soluble factors in the tumour microenvironment, such as TGF- β 1, PAI-1 and uPA, can influence the ratio of full length and uPAR (II-III) and thereby potentially effect cell migration and invasion. Resolving how uPAR cleavage is controlled is therefore vital for understanding how OSCC progresses and potentially provides new targets for therapy
Cleavage of the urokinase receptor (uPAR) on oral cancer cells : regulation by transforming growth factor - beta 1 (TGF-beta 1) and potential effects on migration and invasion
Background: Urokinase plasminogen activator (uPA) receptor (uPAR) is up-regulated at the invasive tumour front of human oral squamous cell carcinoma (OSCC), indicating a role for uPAR in tumour progression. We previously observed elevated expression of uPAR at the tumour-stroma interface in a mouse model for OSCC, which was associated with increased proteolytic activity. The tumour microenvironment regulated uPAR expression, as well as its glycosylation and cleavage. Both full-length- and cleaved uPAR (uPAR (II-III)) are involved in highly regulated processes such as cell signalling, proliferation, migration, stem cell mobilization and invasion. The aim of the current study was to analyse tumour associated factors and their effect on uPAR cleavage, and the potential implications for cell proliferation, migration and invasion. Methods: Mouse uPAR was stably overexpressed in the mouse OSCC cell line AT84. The ratio of full-length versus cleaved uPAR as analysed by Western blotting and its regulation was assessed by addition of different protease inhibitors and transforming growth factor - beta 1 (TGF-beta 1). The role of uPAR cleavage in cell proliferation and migration was analysed using real- time cell analysis and invasion was assessed using the myoma invasion model. Results: We found that when uPAR was overexpressed a proportion of the receptor was cleaved, thus the cells presented both full-length uPAR and uPAR (II-III). Cleavage was mainly performed by serine proteases and urokinase plasminogen activator (uPA) in particular. When the OSCC cells were stimulated with TGF-beta 1, the production of the uPA inhibitor PAI-1 was increased, resulting in a reduction of uPAR cleavage. By inhibiting cleavage of uPAR, cell migration was reduced, and by inhibiting uPA activity, invasion was reduced. We could also show that medium containing soluble uPAR (suPAR), and cleaved soluble uPAR (suPAR (II-III)), induced migration in OSCC cells with low endogenous levels of uPAR. Conclusions: These results show that soluble factors in the tumour microenvironment, such as TGF-beta 1, PAI-1 and uPA, can influence the ratio of full length and uPAR (II-III) and thereby potentially effect cell migration and invasion. Resolving how uPAR cleavage is controlled is therefore vital for understanding how OSCC progresses and potentially provides new targets for therapy.Peer reviewe
Iterative Design and in Vivo Evaluation of an Oncolytic Antilymphoma Peptide
Oncolytic
peptides represent a promising new strategy within the
field of cancer immunotherapy. Here we describe the systematic design
and evaluation of short antilymphoma peptides within this paradigm.
The peptides were tested in vitro and in vivo to identify a lead compound
for further evaluation as novel oncolytic immunotherapeutic. In vitro
tests revealed peptides with high activity against several lymphoma
types and low cytotoxicity toward normal cells. Treated lymphoma cells
exhibited a reduced mitochondrial membrane potential that resulted
in an irreversible disintegration of their plasma membranes. No caspase
activation or ultrastructural features of apoptotic cell death were
observed. One of these peptides, <b>11</b>, was shown to induce
complete tumor regression and protective immunity following intralesional
treatment of murine A20 B-lymphomas. Due to its selectivity for lymphoma
cells and its ability to induce tumor-specific immune responses, <b>11</b> has the potential to be used in intralesional treatment
of accessible lymphoma tumors