Polymeric micelles are widely used for the delivery of hydrophobic drugs. However, several highly potent and ubiquitously used anticancer drugs are water-soluble, complicating their (co-) formulation in polymeric micelles without having to chemically modify them. We here explore hydrophobic ion pairing to enable the co-delivery of the water-soluble anthracycline chemotherapy drug doxorubicin and the angiotensin II receptor antagonist telmisartan (a clinically used antihypertensive drug that has...
One of the biggest challenges for siRNA-based therapeutics is intracellular delivery into the target cell, which can be facilitated by encapsulating siRNA in lipid nanoparticles (LNPs). In this study, we formulated D-Lin-MC3-DMA-LNPs encapsulating siRNA against the androgen receptor (AR), a key driver in prostate cancer. We effectively knocked down AR expression at both the mRNA as well as protein levels in vitro in AR-expressing prostate cancer cell lines. However, when moving to in vivo...
The continued emergence and zoonotic threat posed by coronaviruses highlight the urgent need for effective antiviral strategies with broad reactivity to counter new emerging strains. Nanobodies (or single-domain antibodies) are promising alternatives to traditional monoclonal antibodies, due to their small size, cost-effectiveness and ease of bioengineering. Here, we describe 7F, a llama-derived nanobody, targeting the spike receptor binding domain of sarbecoviruses and SARS-like coronaviruses....
Osteoimmunomodulation is a strategy to promote bone regeneration in implants by modifying the immune environment. CpG-containing oligonucleotides type C (CpG ODN C) and Polyinosinic:polycytidylic acid (Poly[I:C]) are analogs of microbial nucleic acids that have been studied for various immunotherapeutic applications. This research investigates the potential of CpG ODN C and Poly(I:C) as an osteoimmunomodulatory agent for bone regenerative purposes. We encapsulated each nucleic acid in a...
Brain tumors are difficult to target and treat. The blood-brain barrier (BBB) limits drug delivery to pathological sites, and standard mono-chemotherapy typically results in suboptimal efficacy and development of drug resistance. We here set out to load a synergistic drug combination in polymeric micelles, and combined them with ultrasound- and microbubble-mediated BBB opening in glioma models in mice. Via high-throughput screening of various chemotherapy combinations in different glioma cell...
Extracellular vesicles (EVs) are cell-derived vesicles secreted by all cell types into the extracellular spaces. EVs comprise a heterogenous population of vesicles that carry bioactive molecules, such as proteins, lipids, and RNAs, which they can deliver to recipient cells. Over the past few years, EVs have been recognized for their vital role in intercellular communication, and thereby in various physiological and pathological processes. In addition, EVs are increasingly being studied as...
In this work we present a new encapsulation method that allows for the controlled release of drugs under simulated small intestinal conditions. This method consists of encapsulation within microbubbles and is characterized by an unprecedented combination of excellent barrier properties and fast and complete triggered release. The method was applied to produce a drink containing taste-masked acetaminophen as a model drug. Micronized acetaminophen (paracetamol) was dispersed in cyclohexane...
Nucleic acid therapeutics are used for silencing, expressing or editing genes in vivo. However, their systemic stability and targeted delivery to bone marrow resident cells remains a challenge. In this study we present a nanotechnology platform based on natural lipoproteins, designed for delivering small interfering RNA (siRNA), antisense oligonucleotides and messenger RNA to myeloid cells and haematopoietic stem and progenitor cells in the bone marrow. We developed a prototype apolipoprotein...
Ficus caricaextract (FCe) is a natural herb that has received a lot of interest in cancer treatment due to its potential anticancer activities against various malignancies. However, due to FCe's low bioavailability and low solubility, its clinical use as an anti-cancer medicine is constrained. The current study aimed to prepare FCe-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) for cancer treatment. Prepared NPs were characterized by UV-v is spectroscopy, dynamic light...
CONCLUSIONS: The results show that this hydrogel system loaded with both dexamethasone polymeric micelles and dexamethasone phosphate loaded liposomes has potential as a local delivery platform for the sequential release of dexamethasone and dexamethasone phosphate, for the intracranial treatment of glioblastoma associated edema.
