In many clinical applications, the transdermal route is used as an alternative approach to avoid the significant limitations associated with oral drug delivery. There is a long history for drug delivery through the skin utilizing transdermal microneedle arrays. Microneedles are reported to be versatile and very efficient devices. This technique has spurred both industrial and scientific curiosity, due to its outstanding characteristics such as painless penetration, affordability, excellent medicinal efficiency, and relative protection. Microneedles possess outstanding properties for diverse biomedical uses such as the delivery of very large substances with ionic and hydrophilic physicochemical properties. Importantly, microneedles are applicable in numerous biomedical fields such as therapy, diagnosis, and vaccine administration. Microneedles are emerging tools that have shown profound potential for biomedical applications. Transdermal microneedle technologies are likely to become a preferred route of therapeutic substances administration in the future since they are effective, painless, and affordable. In this review, we summarize recent advances in microneedles for therapeutic applications. We explore their constituent materials and fabrication methods that improve the delivery of critical therapeutic substances through the skin. We further discuss the practicality of advanced microneedles used as drug delivery tools.

Bedaquiline (BDQ) was administered to healthy Sprague-Dawley rats in order to determine its localisation in the brain using mass spectrometry imaging (MSI). This study shows that BDQ has the potential for targeting TB reservoirs in the CNS.

HIV in the central nervous system (CNS) contributes to the development of HIV-associated neurological disorders (HAND), even with chronic antiretroviral therapy. In order for antiretroviral therapy to be effective in protecting the CNS, these drugs should have the ability to localize in brain areas known to be affected by HIV. Consequently, this study aimed to investigate the localization patterns of three first-line antiretroviral drugs, namely, efavirenz, tenofovir, and emtricitabine, in the rat brain. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) and matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) were utilized to assess the pharmacokinetics and brain spatial distribution of the three drugs. Each drug was administered (50 mg/kg) to healthy female Sprague–Dawley rats via intraperitoneal administration. LC–MS/MS results showed that all three drugs could be delivered into the brain, although they varied in blood–brain barrier permeability. MALDI-MSI showed a high degree of efavirenz localization across the entire brain, while tenofovir localized mainly in the cortex. Emtricitabine distributed heterogeneously mainly in the thalamus, corpus callosum, and hypothalamus. This study showed that efavirenz, tenofovir, and emtricitabine might be a potential drug combination antiretroviral therapy for CNS protection against HAND.

Lansoprazole (LPZ) is a commercially available proton-pump inhibitor whose primary metabolite, lansoprazole sulfide (LPZS) was recently reported to have in vitro and in vivo activity against Mycobacterium tuberculosis. It was also reported that a 300 mg kg oral administration of LPZS was necessary to reach therapeutic levels in the lung, with the equivalent human dose being unrealistic. A validated liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for the simultaneous quantification LPZ and LPZS in rat plasma and lung homogenates was developed. We administered 15 mg kg oral doses of LPZ to a healthy rat model to determine the pharmacokinetics of its active metabolite, LPZS, in plasma and lung tissue. We found that the LPZS was present in amounts that were below the limit of quantification. This prompted us to administer the same dose of LPZS to the experimental animals intraperitoneally (i.p.). Using this approach, we found high concentrations of LPZS in plasma and lung, 7841.1 and 9761.2 ng mL , respectively, which were significantly greater than the minimum inhibitory concentration (MIC) for Mycobacterium tuberculosis. While oral and i.p. administration of LPZ resulted in significant concentrations in the lung, it did not undergo sufficient cellular conversion to its anti-TB metabolite. However, when LPZS itself was administered i.p., significant amounts penetrated the tissue. These results have implications for future in vivo studies exploring the potential of LPZS as an anti-TB compound.

As one of the most cutting-edge and promising polymer crosslinked network nanoparticle systems. Polymer nano-sized hydrogels (nanogels) have been a hot topic in the biomedical field over the last few decades. Due to their unique characteristics, which include their relatively high drug encapsulation efficiency, ease of preparation, high tunability, low toxicity, high stability in serum and responsive behavior to a range of stimuli to facilitate drug release. Nanogels are thought to be the next generation of drug delivery systems that can completely change the way that drug delivery systems have an impact on patients’ lives. Nanogels have demonstrated significant potential in a variety of fields, including chemotherapy, diagnosis, organ targeting, and delivery of bioactive molecules of different dimensions. However, the lack of substantial clinical data from nanogels becomes one of the major barriers to translating the nanogel concept into a practical therapeutic application for many disease conditions. In addition, nanogel safety profiles have been the major concern that hinders it advancement to the clinical trial phase. This review aims to emphasize the unique properties of nanogels as delivery systems for a variety of bioactive molecules over other nano-delivery systems. Also, this review attempts to give insight into the recent progress in nanogels as a carrier in the field of nanomedicine to overcome complex biological barriers. Relevant scientific data and clinical rationale for the development and the potential use of nanogel as a carrier for targeted therapeutic interventions are discussed. Finally, the concluding points of this review highlight the importance of understanding the long-term toxicity profile of nanogel within the biological system to fully understand their biocompatibility.

β-lactams are the most prescribed class of antibiotics due to their potent, broad-spectrum antimicrobial activities. However, alarming rates of antimicrobial resistance now threaten the clinical relevance of these drugs, especially for the carbapenem-resistant Enterobacterales expressing metallo-β-lactamases (MBLs). Antimicrobial agents that specifically target these enzymes to restore the efficacy of last resort β-lactam drugs, that is, carbapenems, are therefore desperately needed. Herein, we present a cyclic zinc chelator covalently attached to a β-lactam scaffold (cephalosporin), that is, BP1. Observations from in vitro assays (with seven MBL expressing bacteria from different geographies) have indicated that BP1 restored the efficacy of meropenem to ≤ 0.5 mg/L, with sterilizing activity occurring from 8 h postinoculation. Furthermore, BP1 was nontoxic against human hepatocarcinoma cells (IC50 > 1000 mg/L) and exhibited a potency of (K iapp) 24.8 and 97.4 μM against Verona integron-encoded MBL (VIM-2) and New Delhi metallo β-lactamase (NDM-1), respectively. There was no inhibition observed from BP1 with the human zinc-containing enzyme glyoxylase II up to 500 μM. Preliminary molecular docking of BP1 with NDM-1 and VIM-2 sheds light on BP1’s mode of action. In Klebsiella pneumoniae NDM infected mice, BP1 coadministered with meropenem was efficacious in reducing the bacterial load by >3 log10 units’ postinfection. The findings herein propose a favorable therapeutic combination strategy that restores the activity of the carbapenem antibiotic class and complements the few MBL inhibitors under development, with the ultimate goal of curbing antimicrobial resistance.

Rationale The complexity of central nervous system (CNS) drug delivery is the main obstacle with the blood–brain barrier (BBB) known to restrict access of most pharmaceutical drugs into the brain. Mass spectrometry imaging (MSI) offers possibilities for studying drug deposition into the CNS. Methods The deposition and spatial distribution of the two antiretroviral drugs elvitegravir and tenofovir in the brain were investigated in healthy female Sprague–Dawley rats following a single intraperitoneal administration (50 mg/kg). This was achieved by the utilization of quantitative liquid chromatography/tandem mass spectrometry (LC/MS/MS) and matrix‐assisted laser desorption/ionization (MALDI) MSI. Results LC/MS/MS showed that elvitegravir has better BBB penetration, reaching maximum concentration in the brain (Cmaxbrain) of 976.5 ng/g. In contrast, tenofovir displayed relatively lower BBB penetration, reaching Cmaxbrain of 54.5 ng/g. MALDI‐MSI showed the heterogeneous distribution of both drugs in various brain regions including the cerebral cortex. Conclusions LC/MS/MS and MALDI‐MSI provided valuable information about the relative concentration and the spatial distribution of the two common antiretroviral drugs. This study has also shown the capability of MALDI‐MSI for direct visualization of pharmaceutical drugs in situ.

Psoriasis vulgaris (PV) is a common chronic disease, affecting much of the population. Hydrocortisone (HCT) is currently utilized as a PV treatment; however, it is associated with undesirable side effects. The aim of this research was to create a thermo-responsive nano-hydrogel delivery system. HCT-loaded sorbitan monostearate (SMS)-polycaprolactone (PCL) nanoparticles, encapsulated with thermo-responsive hydrogel carboxymethyl cellulose (CMC), were synthesized by applying the interfacial polymer-deposition method following solvent displacement. The nanoparticles’ properties were evaluated employing Differential Scanning Colorimetry, Thermogravimetric Analysis, Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, Zeta sizer, Ultraviolet/Visual spectroscopy, and cytotoxicity testing. The nanoparticle sizes were 110.5 nm, with polydispersity index of 0.15 and zeta potential of −58.7 mV. A drug-entrapment efficacy of 76% was attained by the HCT-loaded SMS-PCL nanoparticles and in vitro drug-release profiles showed continuous drug release over a period of 24 hrs. Keratinocyte skin cells were treated with HCT-loaded SMS-PCL nanoparticles encapsulated with CMC; the results indicated that the synthesized drug-delivery system was less toxic to the keratinocyte cells compared to HCT. The combined trials and results from the formulation of HCT-loaded SMS-PCL nanoparticles encapsulated with CMC showed evidence that this hydrogel can be utilized as a potentially invaluable formulation for transdermal drug delivery of HCT, with improved efficacy and patient conformity.