A poly-δ-decalactone (PDL) based nanoemulgel for topical delivery of ketoconazole and eugenol against Candida albicans.

This study aimed to investigate the potential of poly-δ-decalactone (PDL) and a block copolymer (methoxy-poly(ethylene glycol)-b-poly-δ-decalactone (mPEG-b-PDL)) in the topical delivery of ketoconazole (KTZ) and eugenol (EUG) against Candida albicans. The nanoemulsion (NE) was studied for its significant factors and was optimized using the design of experiments (DOE) methodologies. A simple robust nanoprecipitation method was employed to successfully produce a nanoemulsion (KTZ-EUG-NE). The spherical globules exhibited rough surfaces, explaining the adsorption of mPEG-b-PDL onto PDL. The sustained drug release effects were governed by the amorphous nature of PDL. KTZ-EUG-NE was further used to develop a 1% w/v Carbopol-940-based nanoemulgel (KTZ-EUG-NE gel). The optimal rheological and spreadability properties of the developed nanoemulgel explain the ease of topical applications. Ex vivo permeation and retention studies confirmed the accumulation of KTZ-EUG-NE at different layers of the skin when applied topically. The cytotoxicity of the developed NE in human keratinocyte (HaCaT) cells demonstrated the utility of this newly explored nanocarrier in reducing the cell toxicity of KTZ. The higher antifungal activities of KTZ-EUG-NE at 19.23-fold lower concentrations for planktonic growth and 4-fold lower concentrations for biofilm formation than coarse drugs explain the effectiveness of the developed NE.

A nanotechnology driven effectual localized lung cancer targeting approaches using tyrosine kinases inhibitors: Recent progress, preclinical assessment, challenges, and future perspectives.

The higher incidence and mortality rate among all populations worldwide explains the unmet solutions in the treatment of lung cancer. The evolution of targeted therapies using tyrosine kinase inhibitors (TKI) has encouraged anticancer therapies. However, on-target and off-target effects and the development of drug resistance limited the anticancer potential of such targeted biologics. The advances in nanotechnology-driven-TKI embedded carriers that offered a new path toward lung cancer treatment. It is the inhalation route of administration known for its specific, precise, and efficient drug delivery to the lungs. The development of numerous TKI-nanocarriers through inhalation is proof of TKI growth. The future scopes involve using potential lung cancer biomarkers to achieve localized active cancer-targeting strategies. The adequate knowledge of in vitro absorption models usually helps establish better in vitro - in vivo correlation/extrapolation (IVIVC/E) to successfully evaluate inhalable drugs and drug products. The advanced in vitro and ex vivo lung tissue/ organ models offered better tumor heterogeneity, etiology, and microenvironment heterogeneity. The involvement of lung cancer organoids (LCOs), human organ chip models, and genetically modified mouse models (GEMMs) has resolved the challenges associated with conventional in vitro and in vivo models. To access potential inhalation-based drugtherapies, biological barriers, drug delivery, device-based challenges, and regulatory challenges must be encountered associated with their development. A proper understanding of material toxicity, size-based particle deposition at active disease sites, mucociliary clearance, phagocytosis, and the presence of enzymes and surfactants are required to achieve successful inhalational drug delivery (IDD). This article summarizes the future of lung cancer therapy using targeted drug-mediated inhalation using TKI.

Nanomedicine for colon-targeted drug delivery: strategies focusing on inflammatory bowel disease and colon cancer.

The nanostructured drug-delivery systems for colon-targeted drug delivery are a promising field of research for localized diseases particularly influencing the colonic region, in other words, ulcerative colitis, Crohn's disease, and colorectal cancer. There are various drug-delivery approaches designed for effective colonic disease treatment, including stimulus-based formulations (enzyme-triggered systems, pH-sensitive systems) and magnetically driven drug-delivery systems. In addition, targeted drug delivery by means of overexpressed receptors also offers site specificity and reduces drug resistance. It also covers GI tract-triggered emulsifying systems, nontoxic plant-derived nanoformulations as advanced drug-delivery techniques as well as nanotechnology-based clinical trials toward colonic diseases. This review gives insight into advancements in colon-targeted drug delivery to meet site specificity or targeted drug-delivery requirements.

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Recent Advances in the Use of Cubosomes as Drug Carriers with Special Emphasis on Topical Applications.

Topical drug delivery employing drug nanocarriers has shown prominent results in treating topical ailments, especially those confined to the skin and eyes. Conventional topical formulations persist with drug and disease-related challenges during treatment. Various nanotechnology-driven approaches have been adopted to mitigate the issues associated with conventional formulations. Among these, cubosomes have shown potential applications owing to their liquid crystalline structure, which aids in bioadhesion, retention, sustained release, and loading hydrophilic and hydrophobic moieties. The phase transition behavior of glyceryl monooleate, the concentration of stabilizers, and critical packing parameters are crucial parameters that affect the formation of cubosomes. Microfluidics-based approaches constitute a recent advance in technologies for generating stable cubosomes. This review covers the recent topical applications of cubosomes for treating skin (psoriasis, skin cancer, cutaneous candidiasis, acne, and alopecia) and eye (fungal keratitis, glaucoma, conjunctivitis, and uveitis) diseases. The article summarizes the manufacturing and biological challenges (skin and ocular barriers) that must be considered and encountered for successful clinical outcomes. The patented products are successful examples of technological advancements within cosmeceuticals that support various topical applications with cubosomes in the pharmaceutical field.

Hepatocellular carcinoma: Preclinical and clinical applications of nanotechnology with the potential role of carbohydrate receptors.

Hepatocellular carcinoma (HCC) is one of the most common types of liver cancer; accounts for 75-85% of cases. The treatment and management of HCC involve different sanative options like surgery, chemotherapy, immunotherapy, etc. Recently, various advancements have been introduced for the diagnosis and targeting of hepatic tumor cells. Among these, biomarkers are considered the primary source for the diagnosis and differentiation of tumor cells. With the advancement in the field of nanotechnology, different types of nanocarriers have been witnessed in tumor targeting. Nanocarriers such as nanoparticles, liposomes, polymeric micelles, nanofibers, etc. are readily prepared for effective tumor targeting with minimal side-effects. The emergence of various approaches tends to improve the effectiveness of these nanocarriers as demonstrated in ample clinical trials. This review focuses on the significant role of carbohydrates such as mannose, galactose, fructose, etc. in the development, diagnosis, and therapy of HCC. Hence, the current focus of this review is to acknowledge various perspectives regarding the occurrence, diagnosis, treatment, and management of HCC.

Overcoming skin barriers through advanced transdermal drug delivery approaches.

Upon exhaustive research, the transdermal drug delivery system (TDDS) has appeared as a potential, well-accepted, and popular approach to a novel drug delivery system. Ease of administration, easy handling, minimum systemic exposure, least discomfort, broad flexibility and tunability, controlled release, prolonged therapeutic effect, and many more perks make it a promising approach for effective drug delivery. Although, the primary challenge associated is poor skin permeability. Skin is an intact barrier that serves as a primary defense mechanism to preclude any foreign particle's entry into the body. Owing to the unique anatomical framework, i.e., compact packing of stratum corneum with tight junction and fast anti-inflammatory responses, etc., emerged as a critical physiological barrier for TDDS. Fusion with other novel approaches like nanocarriers, specially designed transdermal delivery devices, permeation enhancers, etc., can overcome the limitations. Utilizing such strategies, some of the products are under clinical trials, and many are under investigation. This review explores all dimensions that overcome poor permeability and allows the drug to attain maximum potential. The article initially compiles fundamental features, components, and design of TDDS, followed by critical aspects and various methods, including in vitro, ex vivo, and in vivo methods of assessing skin permeability. The work primarily aimed to highlight the recent advancement in novel strategies for effective transdermal drug delivery utilizing active methods like iontophoresis, electroporation, sonophoresis, microneedle, needleless jet injection, etc., and passive methods such as the use of liposomes, SLN, NLC, micro/nanoemulsions, dendrimers, transferosomes, and many more nanocarriers. In all, this compilation will provide a recent insight on the novel updates along with basic concepts, the current status of clinical development, and challenges for the clinical translation of TDDS.