Emulsion platforms could be explored for potential delivery of chemotherapeutics in glioblastoma multiforme therapy.
The flow regimes of multiple emulsions in the continuous Couette-Taylor flow (CTF) contactor and characterization of the dispersion state are reported. The proposed method of multiple emulsion preparation is a one-step procedure on the contrary to the classical two-step procedure. The effect of operating parameters in the CTF contactor on multiple emulsion appearance, structure (drop size and packing), and rheological behavior is discussed. The key factors affecting multiple emulsion preparation in the CTF apparatus were the phases ratio, the rotational flow, and an annular gap width. The influence of an axial flow was more significant in the range of small rotational rates. The operating conditions were optimized to find the best characteristic multiple emulsions (largest interfacial area). The paper presents the same exemplary data of using W 1 /O/W 2 emulsions as emulsion liquid membranes (ELMs) in the extraction process and O 1 /W/O 2 for control active agent (drug) release.
The ability to preserve stem cells/cells with minimal damage for short and long periods of time is essential for advancements in biomedical therapies and biotechnology. New methods of cell banking are continuously needed to provide effective damage prevention to cells. This paper puts forward a solution to the problem of the low viability of cells during cryopreservation in a traditional suspension and storage by developing innovative multiple emulsion-based carriers for the encapsulation and cryopreservation of cells. During freezing-thawing processes, irreversible damage to cells occurs as a result of the formation of ice crystals, cell dehydration, and the toxicity of cryoprotectant. The proposed method was effective due to the "flexible" protective structure of multiple emulsions, which was proven by a high cell survival rate, above 90%. Results make new contributions in the fields of cell engineering and biotechnology and contribute to the development of methods for banking biological material.
The advanced use of a pH-responsive biomaterial-based injectable liquid implant for effective chemotherapeutic delivery in glioblastoma multiforme (GBM) brain tumor treatment is presented. As an implant, we proposed a water-in-oil-in-water multiple emulsion with encapsulated doxorubicin. The effectiveness of the proposed therapy was evaluated by comparing the cancer cell viability achieved in classical therapy (chemotherapeutic solution). The experimental study included doxorubicin release rates and consumption for two emulsions differing in drop sizes and structures in the presence of GBM-cells (LN229, U87 MG), and a cell viability. The results showed that the multiple emulsion implant was significantly more effective than classical therapy when considering the reduction in cancer cell viability: 85% for the emulsion-implant, and only 43% for the classical therapy. A diffusion-reaction model was adapted to predict doxorubicin release kinetics and elimination by glioblastoma cells. CFD (computational fluid dynamics) simulations confirmed that the drug release kinetics depends on multiple emulsion structures and drop sizes. | INTRODUCTIONDrug delivery in the treatment of the central nervous system (CNS) diseases (brain tumors, trauma, infections, neurodegenerative problems, among others) requires passing through, or bypassing, the blood-brain barrier (BBB). The methods of drug administration to the CNS can be divided into three main groups: invasive techniques, noninvasive techniques, and alternative routes. [1][2][3] The noninvasive techniques explore approaches in which pharmaceuticals are reengineered to cross the BBB via: (i) chemical methods (lipophilic analogues, prodrugs, enzymatic reactions or chemical bonding of drug molecules with transport facilitated molecules), or (ii) biological methods (drug attachment to proteins specific for receptors responsible for transport across the BBB, transport vectors or barrier-crossing peptides). In addition, nanoparticles, dendrimers, liposomes, micelles, micro/nanoemulsions, including targeted drug delivery systems, and stimuli-responsive functional biomaterials in the drug delivery area, are used to cross the BBB. [4][5][6] The invasive techniques include: (i) local surgical treatment combined with adjuvant therapy (intracerebral polymer implants or microchips, intraventricular/intrathecal or interstitial drug delivery, biological tissue delivery) or (ii) controlled BBB damage with drug delivery (e.g., convection-enhanced drug delivery, osmotic or ultrasound disruption of the BBB). Surgical treatment in combination with radio and chemotherapy, in the case of brain tumors, plays a fundamental role in neurooncology. If possible, tumors should be removed completely. In most cases, only part of the tumor is surgically removed, and the remainder is irradiated or subjected to chemotherapy for destruction. The alternative methods bypass the cardiovascular system and include transnasal administration of drugs or iontophoretic delivery. Modern medicine responds to the needs o...
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