Delving into the Latest Updates on Thermosome GmbH with Synapse

Overview

Tags

Nervous System Diseases

Digestive System Disorders

Hemic and Lymphatic Diseases

Small molecule drug

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Endocrinology and Metabolic Disease	1
Immune System Diseases	1
Nervous System Diseases	1
Hemic and Lymphatic Diseases	1
Infectious Diseases	1
Neoplasms	1

Top 5 Drug Type	Count

Small molecule drug	1

Top 5 Target	Count

Top II(Topoisomerase II)	1

Dexamethasone (DXM) is a potent glucocorticoid with an anti-inflammatory and anti-angiogenic activity which is widely clinically used. Systemic side effects limit the long-term use of DXM in patients requiring formulations which deliver and selectively release the drug to the diseased tissues. This in vitro study compares the suitability of DXM and commonly used prodrugs dexamethasone-21-phosphate (DXMP) and dexamethasone-21-palmitate (DP) as well as DXM complexed by 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD) for the use in thermosensitive liposomes (TSL). DXM showed a poor retention and a low final drug:lipid ratio in a 1,2-dipalmitoyl-sn‑glycero-3-phosphodiglycerol-based TSL (DPPG₂-TSL) and a low-temperature sensitive liposome (LTSL). In contrast to DXM, DXMP and DP were stably retained at 37 °C in TSL in serum and could be encapsulated with high drug:lipid ratios in DPPG₂-TSL and LTSL. DXMP showed a rapid release at mild hyperthermia (HT) from both TSL in serum, whereas DP remained incorporated in the TSL bilayer. According to release experiments with carboxyfluorescein (CF), HP-γ-CD and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) are suitable vehicles for the loading of DXM into DPPG₂-TSL and LTSL. Complexation of DXM with HP-γ-CD increased the aqueous solubility of the drug leading to approx. ten times higher DXM:lipid ratio in DPPG₂-TSL and LTSL in comparison to un-complexed DXM. Both DXM and HP-γ-CD showed increased release at HT in comparison to 37 °C in serum. In conclusion, DXMP and DXM complexed by HP-γ-CD represent promising candidates for TSL delivery.

01 Mar 2022·Journal of Controlled ReleaseQ1 · MEDICINE

Hyperthermia-induced doxorubicin delivery from thermosensitive liposomes via MR-HIFU in a pig model

Q1 · MEDICINE

Article

Author: Lindner, Lars H ; Rademann, Pia ; Toker, Dennis ; Mink, Ben Lasse ; Schubert-Quecke, Claudia ; Simon, Alexandra Claudia ; Grüll, Holger ; Lucas, Christina ; Schmidt, Patrick ; Vlachakis, Susan ; Ekdawi, Sandra ; Hossann, Martin ; Yeo, Sin Yuin ; Castillo Gómez, Juan Daniel ; Brodesser, Susanne ; Sebeke, Lukas Christian ; Heijman, Edwin

PURPOSEEncapsulation of cytotoxic drugs for a localized release is an effective way to increase the therapeutic window of such agents. In this article we present the localized release of doxorubicin (DOX) from phosphatidyldiglycerol (DPPG₂) based thermosensitive liposomes using MR-HIFU mediated hyperthermia in a swine model.MATERIALS AND METHODSGerman landrace pigs of weights between 37.5 and 53.5 kg received a 30-min infusion of DOX containing thermosensitive liposomes (50 mg DOX/m²). The pigs' biceps femoris was treated locally in two separate target areas with mild hyperthermia using magnetic resonance guided high intensity focused ultrasound, starting 10 min and 60 min after initiation of the infusion, respectively. The pharmacokinetics and biodistribution of DOX were determined and an analysis of the treatment parameters' influence was performed.RESULTSCompared to untreated tissue, we found a 15-fold and a 7-fold increase in DOX concentration in the muscle volumes that had undergone hyperthermia starting 10 min and 60 min after the beginning of the infusion, respectively. The pharmacokinetic analysis showed a prolonged circulation time of DOX and a correlation between the AUC of extra-liposomal DOX in the bloodstream and the amount of DOX accumulated in the target tissue.CONCLUSIONSWe have demonstrated a workflow for MR-HIFU hyperthermia drug delivery that can be adapted to a clinical setting, showing that HIFU-hyperthermia is a suitable method for local drug release of DOX using DPPG₂ based thermosensitive liposomes in stationary targets. Using the developed pharmacokinetic model, an optimization of the drug quantity deposited in the target via the timing of infusion and hyperthermia should be possible.

01 Nov 2021·Biochimica et Biophysica Acta (BBA) - BiomembranesQ2 · BIOLOGY

Evaluation of release and pharmacokinetics of hexadecylphosphocholine (miltefosine) in phosphatidyldiglycerol-based thermosensitive liposomes

Q2 · BIOLOGY

Article

Author: Paal, Michael ; Rysin, Alexander ; Vogeser, Michael ; Lindner, Lars H ; Wedmann, Barbara ; Winter, Gerhard ; Hossann, Martin ; Lokerse, Wouter J M

Hexadecylphosphocholine (HePC, Miltefosine) is a drug from the class of alkylphosphocholines with an antineoplastic and antiprotozoal activity. We previously reported that HePC uptake from thermosensitive liposomes (TSL) containing 1,2-dipalmitoyl-sn-glycero-3-phosphodiglycerol (DPPG₂) into cancer cells is accelerated at mild hyperthermia (HT) resulting in increased cytotoxicity. In this study, we compared HePC release of different TSL formulations in serum. HePC showed rapid but incomplete release below the transition temperature (T_m) of investigated TSL formulations in serum. Short heating (5 min) to 42 °C increased HePC release from DPPG₂-TSL (T_m = 41 °C) by a factor of two in comparison to body temperature (37 °C). Bovine serum albumin (BSA) induced HePC release from DPPG₂-TSL comparable to serum. Furthermore, multilamellar vesicles (MLV) were capable to extract HePC from DPPG₂-TSL in a concentration- and temperature-dependent manner. Repetitive exposure of DPPG₂-TSL to MLV at 37 °C led to a fast initial release of HePC which slowed down after subsequent extraction cycles finally reaching approx. 50% HePC release. A pharmacokinetic study in rats revealed a biphasic pattern with an immediate clearance of approx. 50% HePC whereas the remaining 50% HePC showed a prolonged circulation time. We speculate that HePC located in the external leaflet of DPPG₂-TSL is rapidly released upon contact with suitable biological acceptors. As demonstrated by MLV transfer experiments, asymmetric incorporation of HePC into the internal leaflet of DPPG₂-TSL might improve HePC retention in presence of complex biological media and still give rise to HT-induced HePC release.

100 Deals associated with Thermosome GmbH

Login to view more data

100 Translational Medicine associated with Thermosome GmbH

Login to view more data

Corporation Tree

Boost your research with our corporation tree data.

login

or

view full example data

Boost your research with our corporation tree data.

Pipeline

Pipeline Snapshot as of 05 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Phase 1 Clinical

1

Login to view more data