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Recent advances in drug delivery technologies utilizing a variety of carriers have resulted in a paradigm shift in the current approach to diagnosis and therapy. Mesoporous silica nanoparticles (MSNs) were developed in response to the need for materials with high thermal, chemical, and mechanical properties. The synthesis, ease of surface functionalization, tunable pore size, large surface area, and biocompatibility of MSNs make them useful in a variety of biomedical applications such as drug delivery, theranostics, and stem cell research. In addition, MSNs have a high capability of delivering actives ranging from small molecules such as drugs and amino acids to larger peptides, vaccines, and antibodies in general. Moreover, MSN-based transdermal delivery has sparked a lot of interest because of the increase in drug stability, permeation, and ease of functionalization. The functionalization of MSNs plays an important role in the efficient delivery of therapeutic agents in a highly controlled manner. This review introduced dermal and transdermal drug delivery systems, explained the anatomy of the skin, and summarized different barriers that affect the transdermal delivery of many therapeutic agents. In addition, the fundamentals of MSNs together with their physicochemical properties, synthesis approaches, raw materials used in their fabrication, and factors affecting their physicochemical properties will be covered. Moreover, the applications of MSNs in dermal and transdermal delivery, the biocompatibility of MSNs in terms of toxicity and safety, and biodistribution will be explained with the help of a detailed literature review. The review is covering the current and future perspectives of MSNs in the pharmaceutical field with therapeutic applications., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Irbesartan (IR) is an angiotensin II receptor antagonist drug with antihypertensive activity. IR bioavailability is limited due to poor solubility and first-pass metabolism. The current investigation aimed to design, develop, and characterize the cyclodextrin(s) (CD) complexed IR (IR-CD) loaded solid lipid nanoparticles (IR-CD-SLNs) for enhanced solubility, sustained release behavior, and subsequently improved bioavailability through oral administration. Based on phase solubility studies, solid complexes were prepared by the coacervation followed by lyophilization method and characterized for drug content, inclusion efficiency, solubility, and in vitro dissolution. IR-CD inclusion complexes demonstrated enhancement of solubility and dissolution rate of IR. However, the dissolution efficiency was significantly increased with hydroxypropyl-βCD (HP-βCD) inclusion complex than beta-CD (βCD). SLNs were obtained by hot homogenization coupled with the ultrasonication method with IR/HP-βCD inclusion complex loaded into Dynasan 112 and glycerol monostearate (GMS). SLNs were evaluated for physicochemical characteristics, in vitro release, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and physical stability at room temperature for two months. The optimized SLNs formulation showed particle size, polydispersity index, zeta potential, assay, and entrapment efficiency of 257.6 ± 5.1 nm, 0.21 ± 0.03, -30.5 ± 4.1 mV, 99.8 ± 2.5, and 93.7 ± 2.5%, respectively. IR-CD-SLN and IR-SLN dispersions showed sustained release of IR compared to the IR-CD inclusion complexes. DSC results complimented PXRD results by the absence of IR endothermic peak. Optimized IR-CD complex, IR-SLN, and IR-CD-SLN formulations were stable for two months at room temperature. Thus, the current IR oral formulation may exhibit improved oral bioavailability and prolonged antihypertensive activity, which may improve therapeutic outcomes in the treatment of hypertension and heart failure.