Current Drug Delivery - Volume 22, Issue 6, 2025

Pharmaceutical grade sugars manufactured under Current Good Manufacturing Practice (cGMP) and complied with International Pharmaceutical Excipients Council (IPEC) quality standards, also contain a significant amount of nano-particulate impurities (NPIs). This review will focus on the origin of NPIs, the mechanism of their interference with Dynamic light scattering (DLS) and endotoxin tests, filtration technology to effectively reduce the NPIs, methodologies for analytical quantification of NPIs, guidance for setting the limits of threshold concentration and the overall impact of NPIs on the therapeutic activity, performance, stability of biopharmaceuticals and protein-based formulations. NPIs with an average particle size of 100 to 200 nm are present in sugars and are a combination of various chemicals such as dextrans (with the presence of β-glucans), ash, inorganic metal salts, aromatic colorants, etc. These NPIs primarily originate from raw materials and cannot be removed during the sugar refinement process. While it is commonly believed that filtering the final formulation with a 0.22 μ sterilizing grade filter removes all microbes and particles, it is important to note that NPIs cannot be filtered using this standard sterile filtration technology. Exceeding the threshold limit of NPIs can have detrimental effects on formulations containing proteins, monoclonal Antibodies (mAbs), nucleic acids, and other biopharmaceuticals. NPIs and β-glucans have a critical impact on the functionality and therapeutic activity of biomolecules and if present below the threshold limit of reaction, stability and shelf-life of biologics formulation will be greatly improved and the risk of immunogenic reactions must be significantly decreased.

Phytoconstituents have been widely used since ancient times to form a complex with phospholipids due to their various therapeutic actions. Despite having strong pharmacodynamic efficiency, numerous phytoconstituents have shown lower in vivo bioavailability and few adverse effects. Phytochemicals soluble in water exhibit poor absorption, leading to a limited therapeutic impact. Phytosome nanotechnology overcomes this limitation by creating a bound of phytochemicals with phospholipids. This method exhibits improved absorption because phytosomes inhibit significant herbal extract components from being degraded by gastric juices and gut flora. This improves bioavailability, increases clinical benefit, and ensures delivery to tissues without compromising nutritional stability. This review also aims to highlight those vesicular systems that could be used in phytosome technology. Additionally, this review highlights the preparation, advantage, characterization, applications, and recent development of phytosome and ethosome with a list of recent patents and marketed formulations and their uses.

The intricate anatomical and physiological barriers that prohibit pharmaceuticals from entering the brain continue to provide a noteworthy hurdle to the efficient distribution of medications to brain tissues. These barriers prevent the movement of active therapeutic agents into the brain. The present manuscript aims to describe the various aspects of brain-targeted drug delivery through the nasal route. The primary transport mechanism for drug absorption from the nose to the brain is the paracellular/extracellular mechanism, which allows for rapid drug transfer. The transcellular/intracellular pathway involves the transfer across a lipoidal channel, which regulates the entry or exit of anions, organic cations, and peptides. Spectroscopy and PET (positron emission tomography) are two common methods used for assessing drug distribution. MRI (Magnetic resonance imaging) is another imaging method used to assess the efficacy of aerosol drug delivery from nose to brain. It can identify emphysema, drug-induced harm, mucus discharge, oedema, and vascular remodeling. The olfactory epithelium's position in the nasal cavity makes it difficult for drugs to reach the desired target. Bi-directional aerosol systems and tools like the “OptiNose” can help decrease extranasal particle deposition and increase particle deposition efficiency in the primary nasal pathway. Direct medicine administration from N-T-B, however, can reduce the dose administered and make it easier to attain an effective concentration at the site of activity, and it has the potential to be commercialized.

The eye is the most delicate organ protected by several complex biological barriers that are static and dynamic. The presence of these ocular barriers retards drug absorption from topically applied dosage forms at the conjunctival sac. The efficient topical delivery of the drug into the globe is more difficult to achieve, and there is a need to develop a topical formulation that may reduce the use of injections and increase patient compliance with decreased frequency of administration. With the advancements of research in nanotechnology, nanoemulsions can be used as biocompatible carriers to deliver the drug to the ocular cavity. The lipophilic globules can increase the solubility of hydrophobic cargos, which provide increased permeation ability and ocular bioavailability, which can sustain drug release and corneal retention. Because of their small size, these formulations do not cause blurring of vision. Over the past decade, Nanoemulsions (NEs) have been used to treat several ocular diseases in the anterior eye segment. This review contains the global economic burden of ocular diseases, challenges in formulating ocular formulations, and recent advances of these NEs as effective carriers for ocular drug delivery, highlighting their performance in pre-clinical studies.

Chronic Obstructive Pulmonary Disease (COPD), a chronic lung disease that causes breathing difficulties and obstructs airflow from the lungs, has a significant global health burden and affects millions of people worldwide. The use of pharmaceuticals in COPD treatment is aimed to alleviate symptoms, improve lung function, prevent exacerbations, and enhance the overall quality of life for patients. Nanotechnology holds great promise to alleviate the burden of COPD. The main goal of this review is to present the full spectrum of therapeutics based on nanostructures for the treatment and management of COPD, including nanoparticles, polymeric nanoparticles, polymeric micelles, solid-lipid nanoparticles, liposomes, exosomes, nanoemulsions, nanosuspensions, and niosomes. Nanotechnology is just one of the many areas of research that may contribute to the development of more effective and personalized treatment modalities for COPD patients in the future. Future studies may be focused on enhancing the therapeutic effectiveness of nanocarriers by conducting extensive mechanistic investigations to translate current scientific knowledge for the effective management of COPD with little or no adverse effects.

Managing bacterial pathogens in the central nervous system is an immense issue for researchers all around the globe. The problem of these infections remains throughout the population, regardless of the discovery of several possible medicines. The major obstacle to drug delivery is the BBB, but only a few medicines that fulfill demanding requirements can penetrate it. Considering inadequate antibiotic alternatives and the increasing development of resistance, it is more important than ever to find new approaches to address this worldwide problem. Medical nanotechnology has evolved as a cutting-edge and effective means of treating many of the most difficult CNS illnesses, including bacterial meningitis. Various metallic nanoparticles, such as gold, silver, and titanium oxide, have shown bactericidal potential. Gold nanoparticles have gotten a great deal of interest due to their excellent biocompatibility, simplicity of surface modification, and optical qualities. The current study described AuNP-based detection and therapy options against meningitis-causing bacteria, including bacterial pathogens' mechanisms for crossing BBB and AuNPs' mode of Action against those bacteria. The current study looked into green synthesized bactericidal gold nanoparticles-based therapy techniques for diagnosing and intervening in bacterial meningitis. Nevertheless, more research is needed before these laboratory findings can be translated into therapeutic trials. Nonetheless, we can confidently assert that the knowledge acquired and addressed in this study will benefit neuro-nanotechnology researchers.

Macrophages are immune cells with high heterogeneity and plasticity, crucial for recognizing and eliminating foreign substances, including cancer cells. However, cancer cells can evade the immune system by producing signals that cause macrophages to switch to a pro-tumor phenotype, promoting tumor growth and progression. Tumor-associated macrophages, which infiltrate into tumor tissue, are important immune cells in the tumor microenvironment and can regulate cancer's growth, invasion, and metastasis by inhibiting tumor immunity. This review article highlights the characteristics of tumor-associated macrophages and their role in the occurrence and development of cancer. It outlines how reprogramming macrophages towards an anti-tumor phenotype can improve the response to cancer therapy. Explore the intricate process of engineered nanoparticles serving as carriers for immunostimulatory molecules, activating macrophages to instigate an anti-tumor response. Finally, it summarizes several studies demonstrating targeting macrophages is a potential in preclinical cancer models. Several challenges must be addressed in developing effective macrophage-targeted therapies, such as the heterogeneity of macrophage subtypes and their plasticity. Further research is needed to understand the mechanisms underlying macrophage function in the tumor microenvironment and identify novel targets for macrophage-directed therapies. Targeting macrophages is a promising and innovative approach to improving cancer therapy and patient outcomes.

Different nanocarriers-based strategies are now extensively being used as an important strategy for improving drug efficacy and responsiveness, reducing toxicity issues related to drugs and harmful side effects, and overcoming the numerous significant difficulties related to absorption and bioavailability. Amongst different nanocarriers, nanovesicles are excellent and versatile systems for effectively delivering therapeutic agents, targeting ligand distribution and location. Nanovesicles are nanosized self-assembling spherical capsules with an aqueous core and one/more lipid(s) layers. Several synthetic nanovesicles have been developed and investigated for their prospective uses in delivering drugs, proteins, peptides, nutrients, etc. Important procedures for nanovesicle manufacturing are thin-film hydration, unshaken method, ethanol injection, ether injection, proliposomes, freeze-drying, hot method, cold method, reverse-phase evaporation, and ultrasonication. Liposomes, liposomes, ethosomes, exosomes, and transferosomes (elastic vesicles) are the nonvesicular candidates extensively investigated to deliver antiviral drugs. This review article comprehensively overview different nanovesicles, their compositions, manufacturing, and applications as potential carriers for effectively delivering different antiviral drugs to treat viral diseases.