Current Drug Delivery - Volume 21, Issue 3, 2024

Skin diseases such as atopic dermatitis affect babies, children, and adults and are characterized by red skin/spots, severe itching that appears on the face, head, legs, neck, and hands, and various causes of illness caused by various external and internal factors. AD is a type IIgE-mediated hypersensitivity reaction. Herbal preparations treat various dermatological diseases like dry skin, melasma, acne, and eczema. Cosmeceuticals are the connection between cosmetics and medicine, one of the world's most used forms of medicine. Cosmeceuticals products are beneficial in treating AD. Herbal cosmetics play a major role in curing various skin diseases. Today, various herbs used in cosmeceuticals have anti-inflammatory, antioxidant, antibacterial, and antiseptic effects. Compared to synthetic preparations, herbal preparations have fewer side effects. This review paper introduces Atopic dermatitis, cosmeceutical, and various phytoconstituents like gallic acid, ferulic acid, boswellic acid, quercetin, and naringenin tetra hydroxyl flavanol glycoside, glycyrrhizic acid, epigallocatechin gallate, etc., used in atopic dermatitis.

Phototherapies, including photothermal therapy and photodynamic therapy, have gained booming development over the past several decades for their attractive non-invasiveness nature, negligible adverse effects, minimal systemic toxicity, and high spatial selectivity. Phototherapy usually requires three components: light irradiation, photosensitizers, and molecular oxygen. Photosensitizers can convert light energy into heat or reactive oxygen species, which can be used in the tumor-killing process. The direct application of photosensitizers in tumor therapy is restricted by their poor water solubility, fast clearance, severe toxicity, and low cellular uptake. The encapsulation of photosensitizers into nanostructures is an attractive strategy to overcome these critical limitations. Poly(glutamic acid) (PGA) is a kind of poly(amino acid)s containing the repeating units of glutamic acid. PGA has superiority for cancer treatment because of its good biocompatibility, low immunogenicity, and modulated pH responsiveness. The hydrophilicity nature of PGA allows the physical entrapment of photosensitizers and anticancer drugs via the construction of amphiphilic polymers. Moreover, the pendent carboxyl groups of PGA enable chemical conjugation with therapeutic agents. In this mini-review, we highlight the stateof- the-art design and fabrication of PGA-based nanoplatforms for phototherapy. We also discuss the potential challenges and future perspectives of phototherapy, and clinical translation of PGA-based nanomedicines.

Background: Mouth-dissolving wafer is polymer-based matrice that incorporates various pharmaceutical agents for oral drug delivery. This polymeric wafer is ingenious in the way that it needs not be administered with water, like in conventional tablet dosage form. It has better compliance among the pediatric and geriatric groups owing to its ease of administration. Objective: The polymeric wafer dissolves quickly in the oral cavity and is highly effective for a targeted local effect in buccal-specific ailments. It is a safe, effective, and versatile drug delivery carrier for a range of drugs used to treat a plethora of oral cavity-specific ailments that inflict common people, like thrush, canker sores, periodontal disease, benign oral cavity tumors, buccal neoplasm, and malignancies. This review paper focuses thoroughly on the present state of the art in mouth-dissolving wafer technology for buccal drug delivery and targeting. Moreover, we have also addressed present-time limitations associated with wafer technology to aid researchers in future developments in the arena of buccal drug delivery. Conclusion: This dynamic novel formulation has tremendous future implications for designing drug delivery systems to target pernicious ailments and diseases specific to the buccal mucosa. In a nutshell, this review paper aims to summarize the present state of the art in buccal targeted drug delivery.

A total of 1534 and 308 articles were published in the journal Current Drug Delivery (CDD), from 2004 and 2019 to 2021, respectively. In this commentary, their impacts were analyzed based on search data about citation times in the Web of Science. These publications were categorized from different standpoints and evaluated in terms of their citations, particularly in the year 2021. The thematic, contemporary, and local features of these articles, as well as the article types and publication formats, were interpreted. Results demonstrated that CDD should be loyal to the contents about drug delivery, particularly nano-drug delivery systems and nano-pharmaceutical technologies. Publications from the developing and developed countries and regions showed no remarkable differences; therefore, submissions are similarly welcomed. Research articles and review articles are the main stream of CDD. The ratio of review papers is about 30%, which is reasonable but should not be further extended. Moreover, open publications with an article processing charge always have a high impact than those with subscription.

The cellular membrane hinders the effective delivery of therapeutics to targeted sites. Cellpenetrating peptide (CPP) is one of the best options for rapidly internalizing across the cellular membrane. CPPs have recently attracted lots of attention because of their excellent transduction efficiency and low cytotoxicity. The CPP-cargo complex is an effective and efficient method of delivering several chemotherapeutic agents used to treat various diseases. Additionally, CPP has become another strategy to overcome some of the current therapeutic agents' limitations. However, no CPP complex is approved by the US FDA because of its limitations and issues. In this review, we mainly discuss the cellpenetrating peptide as the delivery vehicle, the cellular uptake mechanism of CPPs, their design, and some strategies to synthesize the CPP complex via some linkers such as disulfide bond, oxime, etc. Here, we also discuss the recent status of CPPs in the market.

One of the most frequent malignancies in the world is colon cancer. Both men and women are affected in the same way. The colon, which makes up the last part of the digestive system and is where water and minerals from food waste are absorbed, is vulnerable to cancer. The most suitable technique of drug administration is oral administration. Aqueous solubility is low in more than 40% of novel chemical entities, resulting in poor oral drug administration. In the formulation of oral medications, low inconsistent bioavailability is a major challenge. Increasing medication bioavailability is one of the most difficult aspects of pharmacological development. Self-nano-emulsifying drug delivery systems (SNEDDS) have been a potential platform for biopharmaceutical classification system class II and IV drugs for oral delivery. Enhanced bioavailability and solubility, control of toxicity, pharmacological effects, improved stability, improved tissue macrophage dispersion, prolonged delivery, and resistance to physical and chemical degradation are just a few benefits of SNEDDS for herbal drugs. To increase activity and address problems associated with herbal drugs, nanosized modern drug delivery technologies are expected to have a promising future. Improved patient compliance, fewer problems with liquid SNEDDS filled in capsules, and enhanced stability SNEDDS are all benefits of converting liquid SNEDDS to solid oral dosage forms or solid SNEDDS. SNEDDS differs from previous solubility augmentation methods due to its biodegradable components, simplicity of large-scale production, and range of drug-targeting possibilities.

The surface proteins on cell membranes enable the cells to have different properties, such as high biocompatibility, surface modifiability, and homologous targeting ability. Cell-membrane-derived vesicles have features identical to those of their parental cells, which makes them one of the most promising materials for drug delivery. Recently, as a result of the impressive effects of immunotherapy in cancer treatment, an increasing number of researchers have used cell-membrane-derived vesicles to enhance immune responses. To be more specific, the membrane vesicles derived from immune cells, tumor cells, bacteria, or engineered cells have the antigen presentation capacity and can trigger strong anti-tumor effects of the immune system. In this review, we first indicated a brief description of the vesicles and then introduced the detection technology and drug-loading methods for them. Secondly, we concluded the characteristics and applications of vesicles derived from different sources in cancer immunotherapy.

Background and Objectives: Targeted drug is often engulfed and cleared by the reticuloendothelial system in vivo, resulting in reduced treatment efficacy. This study aimed to explore the biodistribution and HER-2-targeted antitumor effects of trastuzumab-modified gold nanorods (Tra-AuNRs) in a gastric cancer animal model. Methods: Gold nanorods were synthesized using a seed-mediated growth method, and then subjected to trastuzumab-targeted modification. Elemental analysis, Fourier transform infrared spectroscopy, and Xray photoelectron spectroscopy were performed; UV-visible absorption peak, photothermal effects, morphology, and size distribution of Tra-AuNRs were characterized. The targeted killing effect of Tra- AuNRs on gastric cancer cells was assessed in vitro. Tra-AuNRs were injected intravenously and intratumorally into gastric cancer-bearing nude mice in vivo and their distribution was detected. Tumor growth inhibition rate and tumor apoptosis-related protein expression were compared between groups. Results: Tra-AuNRs presented a relatively uniform morphology with an average particle size of 59.9 nm and a longitudinal plasmon resonance absorption peak of 790 nm. The targeted killing rate of gastric cancer cells in vitro by Tra-AuNRs was 87.9%. After intravenous injection, Tra-AuNRs were mainly distributed in the liver, tumor, spleen, and lungs. Comparatively, Tra-AuNRs were mainly distributed in the tumor when intratumorally injected, with a tumor concentration of 6.42 μg/g after 24 h. The tumor growth inhibition rate reached 78.3% in the intratumoral injection group, with significantly higher BAX, BAD, and CASPASE-3 expression than that in the intravenous injection group. Conclusion: The findings suggest that Tra-AuNRs can be used for HER-2-positive gastric cancer treatment. Intratumoral injection of Tra-AuNRs significantly increased the local tumor drug concentration and improved the molecular targeted antitumor growth effect in gastric cancer-bearing nude mice.

Background: Liver fibrosis usually progresses to liver cirrhosis and even results in hepatocellular carcinoma, which accounts for one million deaths annually worldwide. To date, anti-liver fibrosis drugs for clinical treatment have not yet been approved. Nowadays, as a natural regulator, Relaxin (RLX) has received increased attention because the expression of RLX could deactivate the activation of hepatic stellate cells (aHSCs) and resolve liver fibrosis. However, its application in treatment is limited due to the short half-life in circulation and low accumulation within the target organ. Methods: To address these problems, a kind of polymeric metformin (PolyMet)-loaded relaxin plasmid (pRLX) core-membrane lipid nanoparticle (PolyMet-pRLX-LNPs, PRLNP) was prepared. Here, PolyMet was used as a carrier to replace the traditional polymer polyethylene diene (PEI), which is of higher toxicity, to prolong the circulation time of pRLX in vivo. Then, the antifibrotic ability of PRLNP to overcome liver fibrosis was carried out in C57BL/6 mice. It is worth mentioning that this is the first time to investigate the potential of PRLNP in carbon tetrachloride-induced liver fibrosis. Results: The results showed that PRLNP effectively downregulated fibrosis-related biomarkers such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Meanwhile, histopathological examinations also showed low collagen accumulation, revealing that PRLNP could histologically and functionally alleviate liver fibrosis. In addition, no significant difference in serum biochemical value between the PRLNP and the normal group, suggesting the safety profile of PRLNP. Conclusion: This research proposed a novel non-toxic treatment method for liver fibrosis with a nanosystem to effectively treat liver fibrosis.

Introduction: Several Testosterone Replacement Therapies exist for hypogonadism, but an in-depth analysis of these products reveals a high dosing frequency and a high drug loading, up to 120 mg for a potent drug like Testosterone. This may lead to patient non-compliance and toxicity problems if used improperly. Androderm^® is the only 24-hour marketed transdermal patch. Testopel pellets are another extended-release product given subcutaneously every 3-6 months. But it requires surgical implantation and is associated with severe adverse effects. For this reason, the development of other extended- release testosterone products is needed. The study aims at using different excipients for the exploration of sustained-release patches. Methods: Reservoir formulations were prepared using Carbomer 941 and HPMC K100M as the sustained- release polymers plus CoTran™ 9702 and CoTran™ 9712 as the release membranes. The formulated patches were subjected to in vitro dissolution for 24 h. The amount of drug release at each time point was determined using the developed HPLC assay. FDA Similarity Factor, f2, t-test, and ANOVA were applied to all nine-point collected samples. Results: CoTran™ 9712 membrane was found to be a better candidate than CoTran™ 9702. The in vitro release profiles of the four formulations were compared (Carbomer vs. HPMC, and CoTran™ 9702 vs. CoTran™ 9712). Conclusion: CoTran™ 9702 releases testosterone significantly lower. Carbomer and CoTran™ 9712 were the best formulation among all with the highest drug release of 2.16 ± 0.36 mg.

Introduction: Methotrexate shows high efficiency in the treatment of Rheumatoid arthritis, but its adverse effects cannot be tolerated by many patients. Additionally, Methotrexate suffers from rapid clearance from blood. Polymeric nanoparticles were used to solve these problems including chitosan. Methods: Herein, a new nanoparticulate system to deliver Methotrexate (MTX) using chitosan nanoparticles (CS NPs) was developed to be used transdermally. CS NPs were prepared and characterized. The drug release was studied in vitro and ex vivo using rat skin. The drug performance in vivo was investigated on rats. Formulations were applied topically once a day on the paws and knee joints of arthritis rats for 6 weeks. Paw thickness was measured and synovial fluid samples were collected. Results: The results showed that CS NPs were monodispersed, and spherical with a size of 279.9 nm and a charge above ± 30mV. Further, 88.02% of MTX was entrapped in the NPs. CS NPs prolonged MTX release and enhanced its permeation (apparent permeability ∼35.00cm/h) and retention (retention capacity ∼12.01%) through rats' skin. The transdermal delivery of MTX-CS NPs improves the progress of the disease compared to free MTX, as reflected by the lower arthritic index values, lower proinflammatory cytokines (TNF-α and IL-6), and higher anti-inflammatory cytokine (IL-10) in the synovial fluid. Further, the oxidative stress activities were significantly higher in the group treated with the MTX-CS NPs, as indicated by GSH. Finally, MTX-CS NPs were more effective in reducing lipid peroxidation in synovial fluid. Conclusion: In conclusion, loading Methotrexate in chitosan nanoparticles controlled its release and enhance its effectiveness against rheumatoid when applied dermally.

Background: Baicalein (BA) is a flavonoid extract from the root of Scutellaria baicalensis Georgi with excellent biological activities, such as antioxidant and anti-inflammatory activities. However, its poor water solubility limits its further development.Objective: This study aims to prepare BA-loaded Solutol HS15 (HS15-BA) micelles, evaluate the bioavailability, and explore protective effects on carbon tetrachloride (CCl4) induced acute liver injury. Methods: The thin-film dispersion method was used to prepare HS15-BA micelles. The physicochemical, in vitro release, pharmacokinetics, and hepatoprotective effects of HS15-BA micelles were studied. Results: The optimal formulation showed a spherical shape by characterization of the transmission electron microscope (TEM) with an average small size (12.50 nm). The pharmacokinetic results illustrated that HS15-BA increased the oral bioavailability of BA. The in vivo results showed that HS15-BA micelles significantly inhibited the activity of the CCl4-induced liver injury marker enzymes aspartate transaminase (AST) and alanine transaminase (ALT). Also, CCl4 induced oxidative damage to liver tissue, leading to increased L-glutathione (GSH) and superoxide dismutase (SOD) activity and decreased malondialdehyde (MDA) activity, while HS15-BA significantly reversed the above changes. Moreover, BA also had a hepatoprotective effect through anti-inflammatory activity; the results of ELISA and RT-PCR revealed that HS15-BA pretreatment significantly inhibited the increase in the expression of inflammatory factors induced by CCl4. Conclusion: In summary, our study confirmed that HS15-BA micelles enhanced the bioavailability of BA, and showed hepatoprotective effects through antioxidant and anti-inflammatory activities. HS15 could be considered a promising oral delivery carrier in treating liver disease.