Design and development of chitosan-insulin-transfersomes (Transfersulin) as effective intranasal nanovesicles for the treatment of Alzheimer's disease: In vitro, in vivo, and ex vivo evaluations.

This study aimed to prepare and characterize chitosan-Transfersulin (CTI) as an effective intranasal drug delivery system (IDDS) for the treatment of memory disorders by mediating insulin (INS) transport into the brain. Tween 80 was used as an edge activator and chitosan (CS) to increase the elasticity of CTI. CTI nanovesicles were prepared by the film hydration method and characterized after optimization. Optimal values of particle size, polydispersity index, zeta potential, encapsulation efficiency, and drug loading were found to be 137.9 ± 28.2 nm, 0.20, + 23.4 mV, 65.1 ± 0.9 %, and 9.1 ± 0.4 %, respectively. The TEM image supported these findings. FTIR and TGA also demonstrated suitable entrapment of INS in CTI without any chemical interaction. The circular dichroism and fluorescence spectroscopy results confirmed INS's stability and structural integrity released from the CTI. The nasal uptake of INS loaded into CTI was confirmed by optical fluorescence imaging. Histological inspections of the hippocampus also confirmed the results of the behavioral tests. In conclusion, these nanoformulations exhibited greater neuroprotective effects on rats via increased intracellular drug uptake and sustained retention, and it appears to be a promising and effective IDDS for treating Alzheimer's disease (AD).

Targeting Multidrug Resistance With Antimicrobial Peptide-Decorated Nanoparticles and Polymers.

As a category of small peptides frequently found in nature, antimicrobial peptides (AMPs) constitute a major part of the innate immune system of various organisms. Antimicrobial peptides feature various inhibitory effects against fungi, bacteria, viruses, and parasites. Due to the increasing concerns of antibiotic resistance among microorganisms, development of antimicrobial peptides is an emerging tool as a favorable applicability prospect in food, medicine, aquaculture, animal husbandry, and agriculture. This review presents the latest research progress made in the field of antimicrobial peptides, such as their mechanism of action, classification, application status, design techniques, and a review on decoration of nanoparticles and polymers with AMPs that are used in treating multidrug resistance. Lastly, we will highlight recent progress in antiviral peptides to treat emerging viral diseases (e.g., anti-coronavirus peptides) and discuss the outlook of AMP applications.

Safety issues of nanomaterials for dermal pharmaceutical products.

Nanomaterials (NMs) have favorable application in the medicine area, specifically in regard to the carry of pharmaceutical ingredients to provide targeted drug delivery systems. The skin is an excellent route for the delivery of pharmaceutical nano-transporters for skin-related applications. The physicochemical properties of nanomaterials such as size, hydrophobicity, loading capacity, charge and weight are vital for a skin penetrating system. Many nanocarriers such as polymeric nanoparticles, inorganic nanomaterials and, lipid nanostructures have been utilized for dermal delivery of active ingredients and others such as carbon nanotubes and fullerenes require more examination for future application in the skin-related area. Some negative side effects and nano-cytotoxicity of nanomaterials require special attention while investigating different nanomaterials for medicinal applications. Then, in the current review, we had a view on the safety issues of nanomaterials for dermal pharmaceutical products.

Portland Cement: An Overview as a Root Repair Material.

Portland cement (PC) is used in challenging endodontic situations in which preserving the health and functionality of pulp tissue is of considerable importance. PC forms the main component of mineral trioxide aggregate (MTA) and demonstrates similar desirable properties as an orthograde or retrograde filling material. PC is able to protect pulp against bacterial infiltration, induce reparative dentinogenesis, and form dentin bridge during the pulp healing process. The biocompatibility, bioactivity, and physical properties of PC have been investigated in vitro and in animal models, as well as in some limited clinical trials. This paper reviews Portland cement's structure and its characteristics and reaction in various environments and eventually accentuates the present concerns with this material. This bioactive endodontic cement has shown promising success rates compared to MTA; however, considerable modifications are required in order to improve its characteristics and expand its application scope as a root repair material. Hence, the extensive chemical modifications incorporated into PC composition to facilitate preparation and handling procedures are discussed. It is still important to further address the applicability, reliability, and cost-effectiveness of PC before transferring into day-to-day clinical practice.

Application of Collagen and Mesenchymal Stem Cells in Regenerative Dentistry.

Collagen is an important macromolecule of Extracellular Matrix (ECM) in bones, teeth, and temporomandibular joints. Mesenchymal Stem Cells (MSCs) interact with the components of the ECM such as collagen, proteoglycans, Glycosaminoglycans (GAGs), and several proteins on behalf of variable matrix elasticity and bioactive cues. Synthetic collagen-based biomaterials could be effective scaffolds for regenerative dentistry applications due to mimicking of host tissues' ECM. These biomaterials are biocompatible, biodegradable, readily available, and non-toxic to cells whose capability promotes cellular response and wound healing in the craniofacial region. Collagen could incorporate other biomolecules to induce mineralization in calcified tissues like bone and tooth. Moreover, the addition of these molecules or other polymers to collagen-based biomaterials could enhance mechanical properties, which is important in load-bearing areas such as the mandible. A literature review was performed via a reliable internet database (mainly PubMed) based on MeSH keywords. This review first describes the properties of collagen as a key protein in the structure of hard tissues. Then, it introduces different types of collagens, the correlation between collagen and MSCs, and the methods used to modify collagen in regenerative dentistry, including recent progression on the regeneration of periodontium, dentin-pulp complex, and temporomandibular joint by applying collagen. The prospects and challenges of collagen-based biomaterials in the craniofacial region are pointd out.

Antimicrobial effects of nanocurcumin gel on reducing the microbial count of gingival fluids of implant‒abutment interface: A clinical study.

Background. This clinical study aimed to prepare and evaluate the effect of antimicrobial nanocurcumin gel on reducing the microbial counts of gingival fluids of the implant‒abutment interface in patients referred to the Tabriz Faculty of Dentistry for the placement of two dental implants. Methods. Fifteen patients applying for at least two dental implants were included in the study. During the uncovering session, nanocurcumin gel was placed in one implant, and no substance was placed in another (the control group). Then, in three sessions, implantation sessions (10 days after the repair abutment closure session), prosthesis delivery (15 days after the implantation session), and one month after prosthesis delivery, the patients' gingival fluid was sampled and cultured to determine bacterial counts in the gingival fluid by colony-forming units (CFU/mL). T-test was used for statistical analysis of data, and statistical significance was set at P<0.05. Results. This study showed that nanocurcumin gel significantly reduced the CFU/mL of gingival fluid in all three sampling stages compared to the control group. Conclusion. According to the results of this study, the application of antimicrobial nanocurcumin gel inside the implant fixture could reduce the microbial counts of gingival fluids.

Osteogenic Differentiation of Mesenchymal Stem Cells via Curcumin-Containing Nanoscaffolds.

The diverse pleiotropic pharmacological effects of curcumin nanoformulations have turned it into an attractive natural compound in different health-related problems. A great body of evidence has shown the impact of curcumin and its nanoformulations on the differentiation of stem cells. The current review highlights cellular and molecular mechanisms connected with the osteogenic differentiation of mesenchymal stem cells (MSCs) in the scaffolds benefiting from the presence of nanocurcumin pointing toward the role of inhibitory or stimulant signal transduction pathways in detail. Moreover, the effects of different concentrations as well as the structural modifications of curcumin on the differentiation of MSCs have been addressed.

A View on Polymerase Chain Reaction as an Outstanding Molecular Diagnostic Technique in Periodontology.

OBJECTIVES: This study presents a discussion on the fundamentals of polymerase chain reaction (PCR) and its use as a diagnostic tool in periodontology. MATERIALS AND METHODS: A computer-aided as well as hand-made search in PubMed and Scopus indexed journals (relevant to the topic) was done by keywords of molecular technique in periodontology, PCR, applications of PCR, and PCR in periodontics. Only the papers in the English language and outlining PCR and its association with periodontology were collected and utilized to provide a succinct review. There was no limitation for publication time. RESULTS: The results of our search showed that PCR has turned into a standard in diagnosis in the field of periodontology. A variety of researches has demonstrated that its sensitive, and specific characteristics make it a quick and effective technique of recognition, identification, and quantification of microorganisms. Identification of various immunoinflammatory markers at the mRNA expression level as well as ascertaining gene-related polymorphisms can also be performed. CONCLUSIONS: The mechanisms of periodontal disease can further become clarified using PCR. Clinical Relevance. PCR as a diagnostic method can play a main part in the validation of the clinical diagnosis of periodontal disease indicating the reason, pathogenesis, clinical steps, progress, and prognosis of the disease.

A comprehensive review of the therapeutic potential of curcumin nanoformulations.

Today, due to the prevalence of various diseases such as the novel coronavirus (SARS-CoV-2), diabetes, central nervous system diseases, cancer, cardiovascular disorders, and so on, extensive studies have been conducted on therapeutic properties of natural and synthetic agents. A literature review on herbal medicine and commercial products in the global market showed that curcumin (Cur) has many therapeutic benefits compared to other natural ingredients. Despite the unique properties of Cur, its use in clinical trials is very limited. The poor biopharmaceutical properties of Cur such as short half-life in plasma, low bioavailability, poor absorption, rapid metabolism, very low solubility (at acidic and physiological pH), and the chemical instability in body fluids are major concerns associated with the clinical applications of Cur. Recently, nanoformulations are emerging as approaches to develop and improve the therapeutic efficacy of various drugs. Many studies have shown that Cur nanoformulations have tremendous therapeutic potential against various diseases such as SARS-CoV-2, cancer, inflammatory, osteoporosis, and so on. These nanoformulations can inhibit many diseases through several cellular and molecular mechanisms. However, successful long-term clinical results are required to confirm their safety and clinical efficacy. The present review aims to update and explain the therapeutic potential of Cur nanoformulations.

A comprehensive review of the therapeutic potential of α-arbutin.

Cosmetic dermatology preparations such as bleaching agents are ingredients with skin-related biological activities for increasing and improving skin beauty. The possibility of controlling skin hyperpigmentation disorders is one of the most important research goals in cosmetic preparations. Recently, cosmetics containing herbal and botanical ingredients have attracted many interests for consumers of cosmetic products because these preparations are found safer than other preparations with synthetic components. However, high-quality trial studies in larger samples are needed to confirm safety and clinical efficacy of phytotherapeutic agents with high therapeutic index. Arbutin (p-hydroxyphenyl-ß-d-glucopyranoside) is a bioactive hydrophilic polyphenol with two isomers including alpha-arbutin (4-hydroxyphenyl-α-glucopyranoside) and ß-arbutin (4-hydroxyphenyl-ß-glucopyranoside). It is used as a medicinal plant in phytopharmacy. Studies have shown that alpha-arbutin is 10 times more effective than natural arbutin. A comparison of IC50 values showed that α-arbutin (with concentration 2.0 mM) has a more potent inhibitory activity on human tyrosinase against natural arbutin (with higher concentration than 30 mM). A review of recent studies showed that arbutin could be beneficial in treatment of various diseases such as hyperpigmentation disorders, types of cancers, central nervous system disorders, osteoporosis, diabetes, etc. This study was designed to describe the therapeutic efficiencies of arbutin.

A promising and effective platform for delivering hydrophilic depigmenting agents in the treatment of cutaneous hyperpigmentation: kojic acid nanostructured lipid carrier.

This study was aimed at preparing and characterising kojic acid nanostructured lipid carriers (KA-NLCs) for delivery to skin. KA-NLCs were prepared using high-speed homogenization followed by ultra-probe sonication method. KA-NLCs were optimized by glyceryl mono-stearate (GMS) and cholesterol (Chol) as solid lipid excipients, oleic acid (OA) as liquid lipid excipient, span 60 (SP 60) and Tween 20 (Tw 20) as co-emulsifiers. For optimized formulation (KA-NLC3), values of particle size, encapsulation efficiency, drug loading, polydispersity index (PDI) and zeta potential (ZP) were found to be 172.9 ± 7.1 nm, 76.4 ± 0.1%, 17.6 ± 1.3%, 0.3 ± 0.1 and -39.1 ± 2.7 mV, respectively. KA-NLC3 was stable at 4 °C and 25 for 3 months. TEM image confirmed these results. ATR-FTIR, DSC and PXRD results indicated suitable entrapment of KA in NLCs without any chemical interaction. The release profile of KA-NLC3 followed a sustained pattern. KA-NLC3 has potent tyrosinase inhibitory activity in comparison with pure KA. Nanoparticles showed a higher antioxidant activity than pure KA. The results of the ex vivo and in vitro percutaneous absorption showed that KA-NLC3 improved percutaneous delivery of KA. Concentrations below 250 µg/mL were determined as suitable concentrations for KA-NLC3. It seems to be biocompatible formulation for the cosmetics aims.

Therapeutic benefits of rutin and its nanoformulations.

BACKGROUND: Rutin as a natural flavonoid compound has revealed an extensive range of therapeutic potentials. PURPOSE: The current paper is focused on the numerous studies on rutin nanoformulations regarding its broad spectrum of therapeutic potentials. STUDY AND METHODS: A review was conducted in electronic databases (PubMed) to identify relevant published literature in English. No restrictions on publication date were imposed. RESULTS: The literature search provided 7,078 results for rutin. Among them, 25 papers were related to the potential biological activities of rutin nanoformulations. Polymeric nanoparticles were the most studied nanoformulations for rutin (14 titles) and lipid nanoparticles (5 titles) were in second place. The reviewed literature showed that rutin has been used as an antimicrobial, antifungal, and anti-allergic agent. Improving the bioavailability of rutin using novel drug-delivery methods will help the investigators to use its useful effects in the treatment of various chronic human diseases. CONCLUSION: It can be concluded that the preparation of rutin nanomaterials for the various therapeutic objects confirmed the enhanced aqueous solubility as well as enhanced efficacy compared to conventional delivery of rutin. However, more investigations should be conducted to confirm the improved bioavailability of the rutin nanoformulations.

An emerging technology in lipid research for targeting hydrophilic drugs to the skin in the treatment of hyperpigmentation disorders: kojic acid-solid lipid nanoparticles.

Kojic acid (KA) as tyrosinase inhibitor shows insufficient skin penetration and several adverse events due topical administration. KA solid lipid nanoparticles (KA-SLNs) were prepared using high speed homogenisation followed by ultra-probe sonication method for improve its effectiveness.KA-SLNs was optimised by Glyceryl mono-stearate (GMS) and Cholesterol (Chol) as lipid excipients and span 60 (SP 60) and Tween 20 (Tw 20) as co-emulsifiers (particle size 156.97 ± 7.15 nm, encapsulation efficiency 59.02 ± 0.74%, drug loading 14.755 ± 1.63%, polydispersity index (PDI) of 0.388 ± 0.004 and zeta potential (ZP) of -27.67 ± 1.89 mV). Optimum formulation (KA-SLN3 dispersion) was stable at 4 and 25 °C for 3 months. Also, TEM image confirmed these results. The results of XRD, DSC and ATR-FTIR analysis indicated that KA was well encapsulated within the SLNs either in molecularly dispersed state and stabilised in amorphous form and there was no chemical interaction between drug and other ingredients. Controlled release was achieved with this formulation. KA-SLN3 dispersion have more tyrosinase inhibition potency in comparison with pure KA. Also, the results of the ex vivo and in vitro percutaneous absorption show that KA-SLN3 dispersion improved percutaneous delivery of KA as a promising and potential novel topical preparation and might open new avenues for treatment of hyperpigmentation disorders.

Applications of nanotechnology in drug delivery to the central nervous system.

In recent years, the researchers and drug designers have given growing attention to new nanotechnology strategies to improve drug delivery to the central nervous system (CNS). Nanotechnology has a great potential to affect the treatment of neurological disorders, mainly Alzheimer's disease, Parkinson's disease, brain tumors, and stroke. With regard to neurodegeneration, several studies showed that nanomaterials have been successfully used for the treatments of CNS disorders. In this regard, nanocarriers have facilitated the targeted delivery of chemotherapeutics resulting in the efficient inhibition of disease progression in malignant brain tumors. Therefore, the most efficacious application of nanomaterials is the use of these substances in the treatment of CNS disease that enhances the overall effect of drug and highlights the importance of nano-therapeutics. This study was conducted to review the evidence on the applications of nanotechnology in designing drug delivery systems with the ability to cross through the blood-brain barrier (BBB) in order to transfer the therapeutic agents to the CNS.

Kojic acid applications in cosmetic and pharmaceutical preparations.

Skin color disorders can be caused by various factors, such as excessive exposure to sunlight, aging and hormonal imbalance during pregnancy, or taking some medications. Kojic acid (KA) is a natural metabolite produced by fungi that has the ability to inhibit tyrosinase activity in synthesis of melanin. The major applications of KA and its derivatives in medicine are based on their biocompatibility, antimicrobial and antiviral, antitumor, antidiabetic, anticancer, anti-speck, anti-parasitic, and pesticidal and insecticidal properties. In addition, KA and its derivatives are used as anti-oxidant, anti-proliferative, anti-inflammatory, radio protective and skin-lightening agent in skin creams, lotions, soaps, and dental care products. KA has the ability to act as a UV protector, suppressor of hyperpigmentation in human and restrainer of melanin formation, due to its tyrosinase inhibitory activity. Also, KA could be developed as a chemo sensitizer to enhance efficacy of commercial antifungal drugs or fungicides. In general, KA and its derivatives have wide applications in cosmetics and pharmaceutical industries.

Application of nanoparticles in percutaneous delivery of active ingredients in cosmetic preparations.

Developments in nanotechnology have expanded novel nanoparticles for several applications, including cosmetic topical preparation. The aim of this article was to review recent literature on percutaneous delivery of cosmetics active ingredient by nanoparticles. The main focus here, is on lipid based nanoparticles since they are of great importance in skin cargo delivery and have vast application in current cosmetic formulations. Data were collected via electronic databases using MeSH keywords, including nanoparticles, lipid particles, cosmetic, dermal delivery and combinations of these words. According to literature nanoparticles play a major role in improving the usefulness of cosmetics. They are able to improve the physiochemical stability of the skin based cosmetic products. Based on data, lipid nanostructures can be added to current cosmetic formulations without any significant problem due to their physical stability and compatibility with other ingredients. However, due to their basically risky nature of nanoparticles, their risk assessment should be taken into consideration.