Paclitaxel-loaded elastic liposomes synthesised by microfluidics technique for enhance transdermal delivery.

The inherent flexibility of elastic liposomes (EL) allows them to penetrate the small skin pores and reach the dermal region, making them an optimum candidate for topical drug delivery. Loading chemotherapy in ELs could improve chemotherapy's topical delivery and localise its effect on skin carcinogenic tissues. Chemotherapy-loaded EL can overcome the limitations of conventional administration of chemotherapies and control the distribution to specific areas of the skin. In the current studies, Paclitaxel was utilised to develop Paclitaxel-loaded EL. As an alternative to the conventional manufacturing methods of EL, this study is one of the novel investigations utilising microfluidic systems to examine the potential to enhance and optimise the quality of Els by the microfluidics method. The primary aim was to achieve EL with a size of < 200 nm, high homogeneity, high encapsulation efficiency, and good stability. A phospholipid (DOPC) combined with neutral and anionic edge activators (Tween 80 and sodium taurocholate hydrate) at various lipid-to-edge activator ratios, was used for the manufacturing of the ELs. A preliminary study was performed to study the size, polydispersity (PDI), and stability to determine the optimum microfluidic parameters and lipid-to-edge activator for paclitaxel encapsulation. Furthermore, physiochemical characterisation was performed on the optimised Paclitaxel-loaded EL using a variety of methods, including Dynamic Light Scattering, Fourier Transform Infrared Spectroscopy, Atomic force microscopy, elasticity, encapsulation efficiency, and In vitro release. The results reveal the microfluidics' significant impact in enhancing the EL characteristics of EL, especially small and controllable size, Low PDI, and high encapsulation efficiency. Moreover, the edge activator type and concentration highly affect the EL characteristics. The Tween 80 formulations with optimised concentration provide the most suitable size and higher encapsulation efficiency. The release profile of the formulations showed more immediate release from the EL with higher edge activator concentration and a higher % of the released dug from the Tween 80 formulations.

Conventional vs PEGylated loaded liposomal formulations by microfluidics for delivering hydrophilic chemotherapy.

Developing drug delivery systems (DDSs) is one of the approaches used to improve cancer treatment, with the main goal of loading cancer drugs into a carrier targeting a specific organ and avoiding the distribution to healthy tissues. Nanoparticles (NPs) have been shown to be one of the optimum carriers that can be used as DDSs. Lipid-based NPs, such as liposomes, have been investigated in the current study due to their low toxicity and ability to carry hydrophilic and hydrophobic molecules. In the current studies, conventional liposomes composed of DPPC, and cholesterol and PEGylated liposomes composed of DPPC, cholesterol, and DSPE-PEG2000 are manufactured and loaded with Carboplatin. The study focused on investigating and comparing the impact of modifying the carboplatin-loaded liposomes with different concentrations of DSPE-PEG2000 on the NP diameter, polydispersity, ζ-potential, encapsulation efficiency (EE%), and drug release. The hydrodynamic microfluidic system was used to investigate any possible improvement in the EE% over other conventional methods. The results showed the microfluidic system's promising effect in enhancing the EE% of the Carboplatin. Moreover, the results showed a smaller diameter and higher stability of the PEGylated liposome. However, conventional liposomes represent better homogeneity and higher encapsulation efficiency for hydrophilic molecules.

Synthesis and Characterization of Paclitaxel-Loaded PEGylated Liposomes by the Microfluidics Method.

For cancer therapy, paclitaxel (PX) possesses several limitations, including limited solubility and untargeted effects. Loading PX into nanoliposomes to enhance PX solubility and target their delivery as a drug delivery system has the potential to overcome these limitations. Over the other conventional method to prepare liposomes, a microfluidic system is used to formulate PX-loaded PEGylated liposomes. The impact of changing the flow rate ratio (FRR) between the aqueous and lipid phases on the particle size and polydispersity index (PDI) is investigated. Moreover, the effect of changing the polyethylene glycol (PEG) lipid ratio on the particle size, PDI, stability, encapsulation efficiency % (EE %), and release profile is studied. The physicochemical characteristics of the obtained formulation were analyzed by dynamic light scattering, FTIR spectroscopy, and AFM. This work aims to use microfluidic technology to produce PEGylated PX-loaded liposomes with a diameter of <200 nm, low PDI < 0.25 high homogeneity, and viable 28 day stability. The results show a significant impact of FRR and PEG lipid ratio on the empty liposomes' physicochemical characteristics. Among the prepared formulations, two formulations produce size-controlled, low PDI, and stable liposomes, which make them preferable for PX encapsulation. The average EE % was >90% for both formulations, and the variation in the PEG lipid ratio affected the EE % slightly; a high packing for PX was reported at different drug concentrations. A variation in the release profiles was notified for the different PEG lipid ratios.

Microfluidic paclitaxel-loaded lipid nanoparticle formulations for chemotherapy.

Nanoparticle technology has promising effects on multiple therapeutic purposes, particularly in controlling drug delivery as Drug Delivery System. The unique properties of nanoparticles significantly enhance drug delivery, efficiency, and toxicity. For cancer therapy, controlling chemotherapy delivery can increase the drug concentration in the desired locations, improve drug efficacy, and limit drug toxicity. Liposomes are used in this project to encapsulate paclitaxel due to their ability to carry hydrophobic molecules, low toxicity, and prolonged half-life. Among the multiple liposome preparation methods, microfluidic technology was used to produce liposomes. Microfluidics excels in other conventional methods by offering a high-level control of the process's parameters, which help control particle size, size distribution, and physiochemical properties. This project aims to produce paclitaxel-loaded liposomes with a diameter below 200 nm with low polydispersity index, high homogeneity, and good stability. Different lipid types (DMPC, DPPC, DSPC, and DOPC) were used with different ratios to investigate their impact on empty liposome formulation. Alongside changing the different microfluidic parameters including the total flow ratio and flow rate ratio to study their effects on liposomes' physiochemical properties. The obtained formulations were tested to analyse different physiochemical properties (DLS, FTIR) and stability studies. DMPC and DPPC are determined to study their encapsulation efficiency and in vitro drug release of paclitaxel at total flow rate 1 ml min-1 and 1:4 flow rate ratio. The paclitaxel-loaded liposomes are subjected to the same physiochemical characteristics and stability study. Promising encapsulation efficiency was reported from both DPPC and DMPC, and sustained drug release was observed.

Microfluidics Technology for the Design and Formulation of Nanomedicines.

In conventional drug administration, drug molecules cross multiple biological barriers, distribute randomly in the tissues, and can release insufficient concentrations at the desired pathological site. Controlling the delivery of the molecules can increase the concentration of the drug in the desired location, leading to improved efficacy, and reducing the unwanted effects of the molecules under investigation. Nanoparticles (NPs), have shown a distinctive potential in targeting drugs due to their unique properties, such as large surface area and quantum properties. A variety of NPs have been used over the years for the encapsulation of different drugs and biologics, acting as drug carriers, including lipid-based and polymeric NPs. Applying NP platforms in medicines significantly improves the disease diagnosis and therapy. Several conventional methods have been used for the manufacturing of drug loaded NPs, with conventional manufacturing methods having several limitations, leading to multiple drawbacks, including NPs with large particle size and broad size distribution (high polydispersity index), besides the unreproducible formulation and high batch-to-batch variability. Therefore, new methods such as microfluidics (MFs) need to be investigated more thoroughly. MFs, is a novel manufacturing method that uses microchannels to produce a size-controlled and monodispersed NP formulation. In this review, different formulation methods of polymeric and lipid-based NPs will be discussed, emphasizing the different manufacturing methods and their advantages and limitations and how microfluidics has the capacity to overcome these limitations and improve the role of NPs as an effective drug delivery system.