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Central nervous system integrity is the state of brain functioning across sensory, cognitive, emotional-social behaviors, and motor domains, allowing a person to realise his full potential. Thus, brain disorders seriously affect patients' quality of life. Efficient drug delivery to treat brain disorders remains a crucial challenge due to numerous brain barriers, particularly the blood-brain barrier (BBB), which greatly impacts the ultimate drug therapeutic efficacy. Lately, nanocarrier technology has made huge progress in overcoming these barriers by improving drug solubility, ameliorating its retention, reducing its toxicity, and targeting the encapsulated agents to different brain tissues. The current review primarily offers an overview of the different components of BBB and the progress, strategies, and contemporary applications of the nanocarriers, specifically lipid-based nanocarriers (LBNs), in treating various brain disorders.

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Eye is the most specialized and sensory body organ and treating eye diseases efficiently is necessary. Despite various attempts, the design of a consummate ophthalmic drug delivery system remains unsolved because of anatomical and physiological barriers that hinder drug transport into the desired ocular tissues. It is important to advance new platforms to manage ocular disorders, whether they exist in the anterior or posterior cavities. Nanotechnology has piqued the interest of formulation scientists because of its capability to augment ocular bioavailability, control drug release, and minimize inefficacious drug absorption, with special attention to lipid-based nanocarriers (LBNs) because of their cellular safety profiles. LBNs have greatly improved medication availability at the targeted ocular site in the required concentration while causing minimal adverse effects on the eye tissues. Nevertheless, the exact mechanisms by which lipid-based nanocarriers can bypass different ocular barriers are still unclear and have not been discussed. Thus, to bridge this gap, the current work aims to highlight the applications of LBNs in the ocular drug delivery exploring the different ocular barriers and the mechanisms viz. adhesion, fusion, endocytosis, and lipid exchange, through which these platforms can overcome the barrier characteristics challenges.

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Propranolol is the first-line drug for managing migraine attacks. D-limonene is a citrus oil known for its neuroprotective mechanism. Thus, the current work aims to design a thermo-responsive intranasal limonene-based microemulsion mucoadhesive nanogel to improve propranolol efficacy. Microemulsion was fabricated using limonene and Gelucire® as the oily phase, Labrasol®, Labrafil®, and deionized water as the aqueous phase, and was characterized regarding its physicochemical features. The microemulsion was loaded in thermo-responsive nanogel and evaluated regarding its physical and chemical properties, in vitro release, and ex vivo permeability through sheep nasal tissues. Its safety profile was assessed via histopathological examination, and its capability to deliver propranolol effectively to rats' brains was examined using brain biodistribution analysis. Limonene-based microemulsion was of 133.7 ± 0.513 nm diametric size with unimodal size distribution and spheroidal shape. The nanogel showed ideal characteristics with good mucoadhesive properties and in vitro controlled release with 1.43-fold enhancement in ex vivo nasal permeability compared with the control gel. Furthermore, it displayed a safe profile as elucidated by the nasal histopathological features. The nanogel was able to improve propranolol brain availability with Cmax 970.3 ± 43.94 ng/g significantly higher than the control group (277.7 ± 29.71 ng/g) and with 382.4 % relative central availability, which confirms its potential for migraine management.

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Benign prostatic hyperplasia (BPH) affects about 90% of men whose ages are over 65. Tadalafil, a selective PDE-5 inhibitor, was approved by FDA for BPH, however, its poor aqueous solubility and bioavailability are considered major drawbacks. This work intended to develop and evaluate oral fast dissolving film containing tadalafil-loaded niosomes for those who cannot receive the oral dosage form. Niosomes were statistically optimized by Box-Behnken experimental design and loaded into a polymeric oral film. Niosomes were assessed for their vesicular size, uniformity, and zeta potential. The thickness, content uniformity, folding endurance, tensile strength, disintegration time, and surface morphology were evaluated for the prepared polymeric film. The optimized niosomes revealed high entrapment efficiency (99.78 ± 2.132%) and the film was smooth with good flexibility and convenient thickness (110 ± 10 µm). A fast release of tadalafil was achieved within 5 min significantly faster than the niosomes-free drug film. The in-vivo bioavailability in rats established that the optimized niosomal film enhanced tadalafil systemic absorption, with higher peak concentration (Cmax = 0.63 ± 0.03 µg/mL), shorter Tmax value (0.66-fold), and relative bioavailability of 118.4% compared to the marketed tablet. These results propose that the oral film of tadalafil-loaded niosomes is a suitable therapeutic application that can be passed with ease to geriatric patients who suffer from BPH.

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Freeze-drying (FD) of nanoparticles, microorganisms, genes, and vaccines is an auspicious technique used to enhance long-term stability and facilitate transportation mainly for products that require specific conditions like cold chains. Although freeze-drying is considered a delicate drying process, it can cause numerous stresses that induce chemical and physical instabilities. Subsequently, the inclusion of suitable excipients along with optimizing the process parameters is crucial to attain stable lyophilizates with high-quality attributes. The current review highlights the state of the art of the freeze-drying process applications in nanoparticulate systems, microorganisms, genes, and vaccine formulations. Moreover, the work focuses on the different stresses facing these systems during FD cycle and the strategies which are utilized for their stabilizations during lyophilization and storage.

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Freeze-drying (FD) is the most substantial drying technique utilized in the pharmaceutical and biopharmaceutical industries. It is a drying process where the solvent is crystallized at low temperatures and then sublimed from the solid-state directly into the vapor phase. Although FD possesses several merits as its suitability for thermolabile materials and its ability to produce dry products with high-quality attributes, it is a complex and prolonged process that requires optimization of both; process and formulation variables. This review attains to disassemble FD complications through a detailed explanation of the lyophilization concept, stages, the factors influencing the process including controlled ice nucleation, and the modified and innovative FD technologies proposed in recent years to overcome the shortage of traditional FD. In addition, this work points out the quality by design (QbD), critical quality of attributes (CQAs), limitations, and drawbacks of lyophilization.HIGHLIGHTSLyophilization is a propitious drying technique for thermolabile materials.Optimizing the lyophilization cycle requires controlling the process parameters.The formulation excipients and the dispersion medium play crucial roles in designing a successful process.Numerous approaches were developed to ameliorate the lyophilization performance.

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Non-steroidal anti-inflammatory drugs (NSAIDs) represent the foundation of pain management caused by inflammatory disorders. Nevertheless, their oral administration induces several side effects exemplified by gastric ulceration, thus, delivering NSAIDs via skin has become an attractive alternative. Herein, microemulsion-based hydrogel (MBH), proliposomal, and cubosomal gels were fabricated, loaded with diclofenac, and physicochemically characterized. The size, charge, surface morphology, and the state of diclofenac within the reconstituted gels were also addressed. The ex-vivo permeation study using Franz cells was performed via the rat abdominal skin. The formulations were assessed in-vivo on mice skin for their irritation effect and their anti-nociceptive efficacy through tail-flick test. Biosafety study of the optimal gel was also pointed out. The gels and their dispersion forms displayed accepted physicochemical properties. Diclofenac was released in a prolonged manner from the prepared gels. MBH revealed a significantly higher skin permeation and the foremost results regarding in-vivo assessment where no skin irritation or altered histopathological features were observed. MBH further induced a significant anti-nociceptive effect during the tail-flick test with a lower tendency to evoke systemic toxicity. Therefore, limonene-containing microemulsion hydrogel is a promising lipid-based vehicle to treat pain with superior safety and therapeutic efficacy.

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Finding out predisposition and makeup alterations in cancer cells has prompted the exploration of exogenous small interference RNA (siRNA) as a therapeutic agent to deal with cancer. siRNA is subjected to many limitations that hinder its cellular uptake. Various nanocarriers have been loaded with siRNA to improve their cellular transportation and have moved to clinical trials. However, many restrictions as low encapsulation efficiency, nanocarrier cytotoxicity and premature release of siRNA have impeded the single nanocarrier use. The realm of nanohybrid systems has emerged to overcome these limitations and to synergize the criteria of two or more nanocarriers. Different nanohybrid systems that were developed as cellular pathfinders for the exogenous siRNA to target cancer will be illustrated in this review.

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The epoch of nanotechnology has authorized novel investigation strategies in the area of drug delivery. Liposomes are attractive biomimetic nanocarriers characterized by their biocompatibility, high loading capacity, and their ability to reduce encapsulated drug toxicity. Nevertheless, various limitations including physical instability, lack of site specificity, and low targeting abilities have impeded the use of solo liposomes. Metal nanocarriers are emerging moieties that can enhance the therapeutic activity of many drugs with improved release and targeted potential, yet numerous barriers, such as colloidal instability, cellular toxicity, and poor cellular uptake, restrain their applicability in vivo. The empire of nanohybrid systems has shelled to overcome these curbs and to combine the criteria of liposomes and metal nanocarriers for successful theranostic delivery. Metallic moieties can be embedded or functionalized on the liposomal systems. The current review sheds light on different liposomal-metal nanohybrid systems that were designed as cellular bearers for therapeutic agents, delivering them to their targeted terminus to combat one of the most widely recognized diseases, cancer.