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Conventional cancer chemotherapy regimens, albeit successful to some extent, suffer from some significant drawbacks, such as high-dose requirements, limited bioavailability, low therapeutic indices, emergence of multiple drug resistance, off-target distribution, and adverse effects. The main goal of developing implantable drug delivery systems (IDDS) is to address these challenges and maintain anti-cancer drugs directly at the intended sites of therapeutic action while minimizing inevitable side effects. IDDS possess numerous advantages over conventional drug delivery, including controlled drug release patterns, one-time drug administration, as well as loading and stabilizing poorly water-soluble chemotherapy drugs. Here, we summarized conventional and novel (three-dimensional (3D) printing and microfluidic) preparation techniques of different IDDS, including nanofibers, films, hydrogels, wafers, sponges, and osmotic pumps. These systems could be designed with high biocompatibility and biodegradability features using a wide variety of natural and synthetic polymers. We also reviewed the published data on these systems in cancer therapy with a particular focus on their release behavior. Various release profiles could be attained in IDDS, which enable predictable, adjustable, and sustained drug releases. Furthermore, multistep or stimuli-responsive drug release could be obtained in these systems. The studies mentioned in this article have proven the effectiveness of IDDS for treating different cancer types with high prevalence, including breast cancer, and aggressive cancer types, such as glioblastoma and liver cancer. Additionally, the challenges in applying IDDS for efficacious cancer therapy and their potential future developments are also discussed. Considering the high potential of IDDS for further advancements, such as programmable release and degradation features, further clinical trials are needed to ensure their efficiency. The overall goal of this review is to expand our understanding of the behavior of commonly investigated IDDS and to identify the barriers that should be addressed in the pursuit of more efficient therapies for cancer. [ABSTRACT FROM AUTHOR]

Current study intended to prepare and evaluate phospholipid-based, mixed micelles (MMs) to improve the ocular delivery of posaconazole (POS), a broad-spectrum antifungal drug. For this, MMs based on egg phosphatidylcholine (EPC), as the main component, in combination with various bile salts (sodium cholate (NaC), sodium deoxycholate (NaDC), sodium taurocholate (NaTC)) or non-ionic surfactants (Pluronic® F-127, Pluronic® F-68, Tween 80, Labrasol® ALF, and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)) were prepared. Particle size, polydispersity index, zeta potential and entrapment efficiency were evaluated to optimize the composition and preparation method of the MMs. Finally, morphology, stability, in vitro release pattern, and in vitro antifungal activity of the optimized formulation were investigated. Among the prepared MMs, vesicles composed of EPC: TPGS with a molar ratio of 70:30, prepared by the thin-film hydration method, showed more appropriate features. Among the prepared MMs, vesicles composed of EPC: TPGS with a molar ratio of 70:30 showed more appropriate features, including an entrapment efficiency (EE) greater than 80%, spherical shape morphology, an average particle size of about 58 nm, desirable stability over a month, slow-release without a noticeable initial burst, and a significantly higher in vitro antifungal activity in comparison with the drug suspension. Therefore, this formulation was selected as the optimal MMs and could be considered as a promising carrier for topical ocular delivery of POS. Graphical Abstract [ABSTRACT FROM AUTHOR]

Considering the limitations of conventional risperidone (RSP) therapies, the present research characterizes the usefulness of multivesicular liposomes (MVLs) as an efficient controlled-release carrier for this widely used antipsychotic drug, to be employed for the treatment of schizophrenia. A 23 full factorial design based on three independent variables was implemented to plan the experiments: the molar ratios of lipid to the drug, triolein to phospholipid, and cholesterol to phospholipid. The impacts of these parameters on the risperidone encapsulation efficiency and its release pattern within the first 24 and 48 h were investigated as dependent variables. Then, the optimized liposomal system was further in-depth analyzed in terms of size, morphological and structural features, release profile over 15 days, biocompatibility, and stability. Optimized formulation parameters gave rise to MVLs possessing a spherical morphology with a median diameter of about 8 μm, a relatively narrow size distribution (span value of 1.49), and an encapsulation efficiency of 57.6%. These carriers not only exhibited a sustained-release behavior in vitro, lasting until the end of the 15 days but also underwent a negligible change in their size and RSP incorporation over two months at refrigerator condition. Furthermore, in vitro cytotoxicity and hemolysis assessments revealed that the optimized MVL formulation is biocompatible. This study revealed the potential of MVLs as a promising system for the delivery of RSP and could open a new vista for the successful management of schizophrenia. [ABSTRACT FROM AUTHOR]

This study was aimed to develop a novel nanocarrier for coenzyme Q10 (CoQ10) by a green process that prevented the use of surfactants and organic solvents. Triglyceride/phospholipid‐based nanocarriers were developed through high‐pressure homogenization (an industrial feasible process), and a 25‐1 fractional factorial design was adopted to assess the influences of formulation variables on the considered responses, including vesicle size, entrapment efficiency, loading capacity, and solubility of the vehicles in simulated gastrointestinal fluids. The optimized formulation was further in‐depth characterized in terms of morphology, release behavior, biocompatibility (Caco‐2 cell cytotoxicity and histological examination), thermal behavior, and Fourier transform infrared analysis. Optimal nanocarriers were found to have mean particle size of 75 nm, narrow particle distribution, and CoQ10 entrapment of 95%. The optimized formulation was stable upon incubation in simulated gastrointestinal fluids without considerable leakage of cargo, which was in agreement with their sustained release behavior. Microscopic observations also confirmed nanosized nature of the vesicles and revealed their spherical shape. Moreover, toxicity evaluations at the cellular and tissue levels revealed their nontoxic nature. In conclusion, triglyceride/phospholipid‐based nanocarriers proved to be a green safe vehicle for delivery of CoQ10 with industrial‐scale production capability and could provide a new horizon for delivery of hydrophobic nutraceuticals. Practical application: Green nanostructure formulation approaches have recently gained tremendous attraction for their safe profile especially when it comes to supplements, which are generally recommended for daily use. However, their sufficient association with cargoes and industrial‐scale production have remained considerable challenges. This study focuses on the development of lipid‐based nanocarriers for CoQ10 by an industrial feasible process that prevents the use of any surfactants or organic solvents. [ABSTRACT FROM AUTHOR]

Sirolimus (rapamycin) is a mammalian target of rapamycin (mTOR) inhibitor with immunosuppressive, antiproliferative, antiangiogenic, antifungal, anti-restenosis and anti-inflammatory properties. However, its clinical application is often hampered by poor aqueous solubility, first-pass metabolism, transport by p-glycoprotein efflux pump, limited oral bioavailability and nonspecific distribution in off-target sites. Recently, various formulation strategies have emerged to overcome these limitations. Among these, pharmaceutical nanotechnology with numerous advantages has great potential for sirolimus delivery. Up to now, the only nanoparticle based FDA approved formulation in the market is Rapamune® tablet which is composed of drug nanocrystals. This review focuses on recent studies that have been investigated various nanostructured carriers such as liposomes, micelles, polymeric nanoparticles, nanocrystals, magnetic nanoparticles, albumin nanoparticles, solid dispersion nanoparticles and niosomes for sirolimus delivery (in organ transplantation, cancer, vascular restenosis, etc.). [ABSTRACT FROM AUTHOR]

Intranasal route, ensuring suitable bioavailability of medicines under circumvention of the gastrointestinal degradation and hepatic first-pass elimination, has been a popular choice for drug delivery. Among nasal dosage forms, mucoadhesive solid inserts have been shown to resist mucociliary clearance and provide a prolonged nasal residence time. Hence, the purpose of this study was the preparation and characterization of nasal inserts composing of polyelectrolyte complexes (PECs) based on k-carrageenan (k-CA) and chitosan (CS) to boost therapeutic efficacy of sumatriptan succinate in the treatment of migraine headache. k-CA/CS PECs were developed in different molar ratios, subjected to lyophilization in small inserts in the presence of sumatriptan succinate, and finally investigated for water uptake ability, mucoadhesive potential, and drug release profile. The formation of PEC between the two polymers was affirmed by Fourier transform infrared spectroscopy (FTIR). Based on the results, it was revealed that the polyanion/polycation molar ratio plays a critical role in modulating the characteristics of the inserts, and among all the formulations, the one comprising k-CA/CS PEC with molar ratio of (4:1), (k-CA/CS(4:1)), demonstrated the highest water uptake ability and mucoadhesive potential and provided a more controlled release of sumatriptan succinate. This study illustrates the potential of the lyophilized inserts based on the k-CA/CS PECs, especially k-CA/CS(4:1), for efficient delivery of sumatriptan succinate via the nasal route of administration and suggests a potential therapeutic approach for the termination of migraine attacks. [ABSTRACT FROM AUTHOR]