Current Drug Delivery - Volume 21, Issue 4, 2024

Exosomes are subtypes of vesicles secreted by almost all cells and can play an important role in intercellular communication. They contain various proteins, lipids, nucleic acids and other natural substances from their metrocytes. Exosomes are expected to be a new generation of drug delivery systems due to their low immunogenicity, high potential to transfer bioactive substances and biocompatibility. However, exosomes themselves are not highly targeted, it is necessary to develop new surface modification techniques and targeted drug delivery strategies, which are the focus of drug delivery research. In this review, we introduced the biogenesis of exosomes and their role in intercellular communication. We listed various advanced exosome drug-loading techniques. Emphatically, we summarized different exosome surface modification techniques and targeted drug delivery strategies. In addition, we discussed the application of exosomes in vaccines and briefly introduced milk exosomes. Finally, we clarified the clinical application prospects and shortcomings of exosomes.

The eye is an important and vital organ of the human body consisting of two segments - anterior and posterior segments and these segments are associated with many diseases. This review elaborates upon the various eye-related diseases with their medications and carriers used to deliver them. Delivery strategies include drugs encapsulated into liposomes, polymeric micelles of drugs, solid lipid nanoparticles, nanostructured lipid carriers, nano emulsions, and Nanosuspension used to improve penetrating properties, bioavailability, and residence time of the drugs as examples available in the literature. With regard to this, different forms of ocular drug delivery are classified and elaborated. Additionally, the possibility of addressing the physical and chemical complexities of ocular diseases and how they could be overcome with environmentally stable nanoformulations are briefly discussed. Enhanced drug delivery efficiency with various novel pharmaceuticals along with enhanced uptake by different routes/modes of drug administration. Current advancements in drug carrier systems, i.e., nanocarriers, have shown promise for improving the retention time, drug permeation and prolonging the duration of release of the drug in the ocular site. Bio-degradable polymers investigated for the preparation of nanocarriers for the entrapment of drugs and to enhance the efficacy through improved adherence of tissue in the eye, sustained release measures, enhanced bioavailability, lower toxicity, and targeted delivery is applicable. This review covers the introduction of various nanocarriers and polymers for ocular drug delivery with the purpose of enhancing the absorption, retention and bioavailability of medications in the eye.

Background: A big health issue facing the world's population is cancer. An alarming increase in cancer patients was anticipated by worldwide demographic statistics, which showed that the number of patients with different malignancies was rapidly increasing. By 2025, probably 420 million cases were projected to be achieved. The most common cancers diagnosed are breast, colorectal, prostate, and lung. Conventional treatments, such as surgery, chemotherapy, and radiation therapy, have been practiced. Objective: In recent years, the area of cancer therapy has changed dramatically with expanded studies on the molecular-level detection and treatment of cancer. Recent advances in cancer research have seen significant advances in therapies such as chemotherapy and immunotherapy, although both have limitations in effectiveness and toxicity. Methods: The development of nanotechnology for anticancer drug delivery has developed several potentials as nanocarriers, which may boost the pharmacokinetic and pharmacodynamic effects of the drug product and substantially reduce the side effects. Results: The advancement in non-viral to viral-based protein-based nanocarriers for treating cancer has earned further recognition in this respect. Many scientific breakthroughs have relied on protein-based nanocarriers, and proteins are essential organic macromolecules for life. It allows targeted delivery of passive or active tumors using non-viral-based protein-based nanocarriers to viral-based protein nanocarriers. When targeting cancer cells, both animal and plant proteins may be used in a formulation process to create self-assembled viruses and platforms that can successfully eradicate metastatic cancer cells. Conclusion: This review, therefore, explores in depth the applications of non-viral to viral proteinbased noncarriers with a specific focus on intracellular drug delivery and anti-cancer drug targeting ability.

The lymphatic system (LS) plays a crucial role in fluid balance, transportation of macromolecules, and immune response. Moreover, LS is a channel for microbial invasion and cancer metastasis. Particularly, solid tumors, including lung, breast, melanoma, and prostate cancers, are metastasized across highways of LS. Subsequently, the fabrication of chimeric lymphatic drug delivery systems (LDDS) is a promising strategy to fight cancer metastasis and control microbial pandemics. In this regard, LDDS, in terms of PEG-nanoscaled lipid carriers, elicited a revolution during the COVID-19 pandemic as cargoes for mRNA vaccines. The drug delivered by the lymphatic pathway escapes first-pass metabolism and enhances the drug's bioavailability. Ample approaches, including synthesis of prodrugs, trigging of chylomicron biosynthesis, and fabrication of nanocarriers, facilitate lymphatic drug delivery. Specifically, nanoscales lipid cargoes have the propensity to lymphatic trafficking. Interestingly, TPGSengineered nanoscale lipid cargoes enhance lymphatic trafficking, increase tissue permeation, and, specifically, uptake. Moreover, they overcome biological barriers, control biodistribution, and enhance organelles localization. Most anticancer agents are non-specific, have low bioavailability, and induced drug resistance. Therefore, TPGS-engineered nanoscale lipid chimeras improve the therapeutic impact of anticancer agents. This review highlights lymphatic cancer metastasis, nanoscales lipid cargoes as LDDS, and their influence on lymphatic trafficking, besides the methods of LDD studies.

Globally, high death rates and poor quality of life are caused mainly by inflammatory diseases. Corticosteroids, which may have systemic side effects and would enhance the risk of infection, are the common forms of therapy. The field of nanomedicine has created composite nanoparticles that carry a pharmacological carrier and target ligands for distribution to sites of inflammation with less systemic toxicity. However, their relatively large size often causes systemic clearance. An interesting approach is metal-based nanoparticles that naturally reduce inflammation. They are made not only to be small enough to pass through biological barriers but also to allow label-free monitoring of their interactions with cells. The following literature review discusses the mechanistic analysis of the anti-inflammatory properties of several metal-based nanoparticles, including gold, silver, titanium dioxide, selenium, and zinc oxide. Current research focuses on the mechanisms by which nanoparticles infiltrate cells and the anti-inflammatory techniques using herbal extracts-based nanoparticles. Additionally, it provides a brief overview of the literature on many environmentally friendly sources employed in nanoparticle production and the mechanisms of action of various nanoparticles.

Objective: To prepare GA-Emo micelles and investigate the feasibility of using GA as both a bifunctional drug and carrier. Methods: The preparation of GA-Emo micelles was accomplished via the thin-film dispersion method with GA as the carrier. Size distribution, entrapment efficiency, and drug loading were used to evaluate the characteristics of micelles. The absorption and transport properties of the micelles in Caco-2 cells were investigated, while their pharmacodynamics in mice were preliminarily studied. Results: The optimal formulation featured a GA/Emo in weight ratio of 2:1 and an encapsulation efficiency of 23.68%. The optimized GA/Emo was characterized as small uniform spheres with an average micellar size of 168.64 ± 5.69 nm, a polydispersity index of 0.17 ± 0.01, and an electrically negative surface (−35.33 ± 0.94 mV). Absorption and transport experiments with Caco-2 cells showed that the absorption of GA-Emo micelles in small intestines was mainly passive transport, amid their transport volume being significantly higher than that of Emo monomer. The intestinal wall thickness of the GAEmo micelles group was significantly lower than that of the Emo group, which meant that the colonic toxicity of the micelles was lower than unincorporated Emo. Conclusion: The advantages of GA as a bifunctional micelle carrier in formulation characters, drug release, and toxicity attenuation provide a new idea for the application of the GA of natural medicine in drug delivery for toxicity reduction.

Objective: The study aimed to develop microspheres of quercetin by oxidative coupling assembly and these microspheres were used to deliver diclofenac sodium without causing gastrotoxicity. Methods: The oxidative coupling assembly of quercetin was carried out in the presence of copper sulfate to yield quercetin microspheres. The microsphere of quercetin was loaded with diclofenac sodium (QP-Diclo). The carrageenan induced paw edema in rats was used for anti-inflammatory action was studied by using and acetic acid-induced writhing in mice was used to study the analgesic potential of the QP loaded microspheres. The ulcerogenecity and gastrotoxicity comparison was made between diclofenac and QP-Diclo. Results: The oxidative coupling assembly of quercetin resulted in microspheres of 10-20 μm in size, which were loaded with diclofenac sodium (QP-Diclo). The marked anti-inflammatory activity was observed by QP-Diclo treatment using carrageenan induced paw edema (in rats) and better analgesic activity than diclofenac sodium in mice. The administration of QP-Diclo significantly elevated the diminished overall nitrite/nitrate extent and thiobarbituric acid reactive and significantly increased the diminished superoxide dismutase activity in comparison to diclofenac sodium in gastric mucosa. Conclusion: The results suggested that dietary polyphenol quercetin can be converted to microspheres by oxidative coupling assembly and can be used to deliver diclofenac sodium without causing gastrotoxicity.

Background: Using targeted liposomes to encapsulate and deliver drugs has become a hotspot in biomedical research. Folated Pluronic F87/D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) co-modified liposomes (FA-F87/TPGS-Lps) were fabricated for curcumin delivery, and intracellular targeting of liposomal curcumin was investigated. Methods: FA-F87 was synthesized and its structural characterization was conducted through dehydration condensation. Then, cur-FA-F87/TPGS-Lps were prepared via thin film dispersion method combined with DHPM technique, and their physicochemical properties and cytotoxicity were determined. Finally, the intracellular distribution of cur-FA-F87/TPGS-Lps was investigated using MCF-7 cells. Results: Incorporation of TPGS in liposomes reduced their particle size, but increased the negative charge of the liposomes as well as their storage stability, and the encapsulation efficiency of curcumin was improved. While, modification of liposomes with FA increased their particle size, and had no impact on the encapsulation efficiency of curcumin in liposomes. Among all the liposomes (cur-F87-Lps, cur-FA-F87-Lps, cur-FA-F87/TPGS-Lps and cur-F87/TPGS-Lps), cur-FA-F87/TPGS-Lps showed highest cytotoxicity to MCF-7 cells. Moreover, cur-FA-F87/TPGS-Lps was found to deliver curcumin into the cytoplasm of MCF-7 cells. Conclusion: Folate-Pluronic F87/TPGS co-modified liposomes provide a novel strategy for drug loading and targeted delivery.

Background: Recent studies have shown that nanoemulsions prepared with essential oils have significant antimicrobial potential against multidrug-resistant pathogens due to increased chemical stability. Nanoemulsion also promotes controlled and sustained release, which increases their bioavailability and efficacy against multidrug-resistant bacteria. Objective: This study aimed to investigate the antimicrobial, antifungal, antioxidant, and cytotoxicity properties of cinnamon essential oil and peppermint essential oil as nanoemulsions compared to pure forms. For this purpose, analyses of the selected stable nanoemulsions were carried out. Method: The droplet sizes and zeta potentials of peppermint essential oil nanoemulsions and cinnamon essential oil nanoemulsions were found to be 154.6±1.42 nm and -17.1±0.68 mV and 200.3±4.71 nm and -20.0±0.81 mV, respectively. Although the amount of essential oil used in nanoemulsions was 25% w/w, antioxidant and antimicrobial activities were found to be more effective compared to pure essential oils. Results: In cytotoxicity studies on the 3T3 cell line, both essential oil nanoemulsions showed higher cell viability than pure essential oils. At the same time, cinnamon essential oil nanoemulsions exhibited a higher antioxidant property than peppermint essential oil nanoemulsions and showed superiority in the antimicrobial susceptibility test conducted against four bacteria and two fungi. Cell viability tests determined that cinnamon essential oil nanoemulsions showed considerably higher cell viability compared to pure cinnamon essential oil. Conclusion: These findings indicated that the prepared nanoemulsions in the current study might positively influence the dosing regimen and clinical outcomes of antibiotic therapy.

Introduction: Increased body fat may influence the partition coefficients of inhaled anesthetics. We compared patient responses to desflurane and sevoflurane anesthesia, as measured by a quicker recovery and fewer complications, in patients with higher body fat percentages, not only obese people. Methods: This study included 120 patients. Participants were stratified into low or high body fat percentages groups using bioelectrical impedance analysis and were randomized 1:1 to receive desflurane or sevoflurane as an inhaled anesthetic, recorded as Low-Desflurane, Low-Sevoflurane, High- Desflurane, and High-Sevoflurane. Recovery time, Riker sedation–agitation scale scores, and complications were recorded over 1 hour in the post-anesthesia care unit. Results: A total of 106 patients were analyzed. There were no significant differences in the overall recovery time between the patient subgroups with higher and lower body fat percentages; in addition, there were no significant differences in the incidence of nausea, vomiting,dizziness, or headache (all p>0.05). However, the incidence of agitation emergence in the HighSevoflurane subgroup was significantly higher compared to the High-Desflurane subgroup (33.3% vs.7.41%; p = 0.043). Conclusion: In conclusion, for patients with a lower body fat percentage, both desflurane and sevoflurane can provide good and fast recovery; for patients with a higher body fat percentage,desflurane may provide better recovery with a lower incidence of agitation emergence compared to sevoflurane.