Current Drug Delivery - Volume 20, Issue 8, 2023

Nanomedicines have been used over time because of their significant impact on human health care for the prevention, early detection, diagnosis, treatment, and follow-up of a wide range of illnesses. Nanomedicines must be adequately characterized in order to develop well-defined nanomedicines with therapeutic value. The surface charge of nanomedicines plays an important role to determine how they interact with biological components where the zeta potential is a useful tool for describing the chemical composition of particle surfaces, such as functional groups, adsorption/desorption, and so on. The main goal of this review is to present an overview of the impact of nanomedicines' surface charges on absorption, distribution, metabolism, and in vivo drug release, for example negatively charged nanoparticles diffuse well through mucus for mucosal drug delivery, whereas positively charged nanoparticles are preferred for transvascular transport, tumor penetration, and cellular absorption. In this review, we also highlight how to improve nanomedicines' therapeutic potential by altering their surface characteristics with the help of various polymers. Future research should be focused on enhancing the therapeutic efficiency of nanomedicines by changing their surface properties, as well as conducting in-depth mechanistic studies by changing the surface properties of nanomedicines for the efficient treatment of diseases with low or no nanomedicine toxicity.

A frequent inflammatory pilosebaceous disorder that affects 80–90% of teenagers, acne vulgaris is still a concern for dermatologists and other doctors in the field of medicine. Acne has a significant psychosocial impact and is responsible for a bigger worldwide burden of disease than psoriasis, cellulitis, and melanoma, as measured by age-standardized disability-adjusted life years. Patients may experience psychological problems as well as severe skin scars as a result of the condition. The pathogenesis process of acne lesion is complex, so it is myriad of available treatment. Acne is caused by a combination of four different pathological causes, including an increase in sebum production, irregular follicular desquamation, P.acnes proliferation, and inflammation of the afflicted skin. Synthetic, hormonal, and herbal treatments, as well as their efficacy in treating acne vulgaris, are discussed in this article. The laser and light treatment for acne vulgaris available within a specific wavelength range that stimulates type I and III collagen and elastic fibres is described in relation to radiation therapies. The innovative drug delivery techniques are covered here, such as particle, vesicular, and colloidal delivery systems as a prospective therapy. We will present a practical method for acne management in this article and discuss how to assess acne, how to use topical therapies, and how systemic therapy can be used to treat acne. This review will inform readers on the most recent advances in our understanding of acne treatment-related technological potential, with a particular emphasis on developing treatment alternatives and creative ways that can assist improve patient results. Acne has been the subject of substantial research, both in terms of disease mechanism and therapeutic approaches. However, as Propionibacterium acnes develop resistance to current medications there is a requirement for novel therapeutic modalities. Additionally, the absence of required data regarding the efficacy of complementary and alternative medicine (CAM) therapies needs a greater investigation into these treatment choices.

With the advent of ivermectin, tremendous improvement in public health has been observed, especially in the treatment of onchocerciasis and lymphatic filariasis that created chaos mostly in rural, sub-Saharan Africa and Latin American countries. The discovery of ivermectin became a boon to millions of people that had suffered in the pandemic and still holds its pharmacological potential. Ivermectin continued to surprise scientists because of its notable role in the treatment of various other tropical diseases (Chagas, leishmaniasis, worm infections, etc.) and is viewed as the safest drug with the least toxic effects. The current review highlights its role in unexplored avenues towards forging ahead of the repositioning of this multitargeted drug in cancer, viral (the evaluation of the efficacy of ivermectin against SARS-Cov-2 is under investigation) and bacterial infection and malaria. This article also provides a glimpse of regulatory considerations of drug repurposing and current formulation strategies. Due to its broad-spectrum activity, multitargeted nature and promising efforts are put towards the repurposing of this drug throughout the field of medicine. This single drug originated from a microbe, changed the face of global health by proving its unmatched success and progressive efforts continue in maintaining its bequestnin the management of global health by decreasing the burden of various diseases worldwide.

Background: Colorectal cancer (CRC) represents one of the most daunting health problems accompanied by progressive undesirable socio-economic effects. Phytochemicals, bioactive ingredients majorly found in plants, have gained momentum for their potential against CRC occurrence and regression. However, these phytoconstituents are not exempt from biopharmaceutical drawbacks; therefore, novel strategies, especially nanotechnology, are exploited to surmount the aforementioned bottlenecks. The current paper aims to comprehensively review the phytochemical-based nanoformulations and their mechanisms in the setting of CRC. Methods: Electronic databases including Scopus, PubMed, and Web of Science were searched with the keywords "colon cancer" or "colorectal cancer", and "plant", "phytochemical", "extract", or "herb", and "nano", "nanoformulation", "Nanoencapsulation", "nanoparticle", "nanostructure", or "nanoliposome", until January 2021. Results: Of the 1230 research hits, only 69 articles were consequently analyzed. The results indicated nanoformulations of several secondary plant metabolites such as berberine, camptothecin, colchicine, apigenin, chrysin, fisetin, quercetin, curcumin, gallic acid, resveratrol, and ursolic acid have profound effects in a broad range of preclinical models of CRC. A wide variety of nanoformulations have been utilized to deliver these phytochemicals, such as nanocomposite, nanocolloids, and mesoporous silica nanoparticles, which have consequently decreased tumor angiogenesis and mitochondrial membrane potential, increased radical scavenging activity, induced cell cycle arrest at different phases of the cancer cell cycle, and induction of apoptosis process via decreased anti-apoptotic proteins (BRAF, CD44, and Bcl-2) and increased in pro-apoptotic ones (Bax, Fas, caspase 3,8, and 9), as well as modulated biopharmaceutical properties. Chitosan and PEG and their derivatives are among the polymers exploited in the phytochemicals’ nanoformulations. Conclusion and perspective: To conclude, nanoformulated forms of natural ingredients depicted outstanding anti-CRC activity that could hold promise for help in treating CRC. However, well-designed clinical trials are needed to build up a whole picture of the health profits of nanoformulation of natural products in CRC management.

A large proportion of new chemical moieties are poorly water-soluble. As a result, the biggest challenge for researchers is to enhance the solubility and oral bioavailability of lipophilic drugs. Self-emulsifying systems offer immense potential for improving lipophilic drugs’ oral bioavailability and solubility through various mechanisms such as: inhibiting efflux transporters, absorption of the lipophilic drug through the lymphatic system, and bypassing hepatic first-pass metabolism. These systems dissolve hydrophobic drugs, allowing them to be delivered in a unit dose form for oral administration. Despite much potential, issues like stability, low drug loading, packaging, etc., are associated with the self-emulsifying technique. This review discusses conventional Self-Emulsifying Drug Delivery Systems (SEDDS), which deliver poorly water-soluble drugs. Recent advancements in self-emulsifying systems to solve the issues associated with conventional SEDDS are described exhaustively, including their methodologies and excipients utilized for preparation. The current article also furnishes a literature review on recent advancements in self-emulsifying systems. Recent advances in SEDDS are a great option for overcoming oral bioavailability, stability, and solubility issues of lipophilic drugs. Solid-self emulsifying system can be used to improve the stability of the formulation, hydrophobic ion-pairing for improving mucus permeation properties, while supersaturated self-emulsifying systems with a low concentration of surfactant to overcome issues such as precipitation of drug after dilution and gastrointestinal related side effects. The day will come when medicine companies will see the value of selfemulsifying system developments and adopt this technology for next-generation product releases.

Currently, various kinds of research are going in the evolution of the Novel Drug Delivery System. NDDS mainly emphasizes the development of a system with improved sustained, controlled, and targeted drug delivery with minimum toxicity. Proniosomes are dry free-flowing formulation that minimizes the drawbacks associated with liposomes and niosomes. Proniosomes are carrier particles that are water-soluble and covered with a surfactant which, upon hydration in a hot aqueous medium with agitation, gives niosomal dispersion. Proniosomes derived niosomes are superior substitutes as compared to other vesicular delivery due to preferable physicochemical properties and improved chemical stability. The proniosomes deliver additional convenience of transportation, storage, distribution, and dosing, which makes dry niosomes a versatile commercial product. This illustrated review emphasizes the components, method of preparation, factors affecting the formation of proniosomes, characterization, and various routes of administration of proniosomes. This review will help to explore the efficacy and functionality of proniosomes in different fields for their upcoming supremacy in the field of drug delivery.

The current article mainly highlights mucoadhesive drug delivery with merits like the prolonged holding time at the action site and also provides a controlled rate of drug release for improved therapeutic outcomes. Moreover, mucosal delivery can eliminate problems of the conventional oral route, such as first pass metabolism as well as acid degradation. However, the eye has unique anatomy and physiology that can cause hindrance and challenges in comparison to the other organs of the body. Additionally, conventional delivery vehicles like solutions, suspensions, and ointments have many demerits such as rapid precorneal clearance, subject variability, drainage, and uncontrolled release from the dosage form. Therefore, novel pharmaceutical ophthalmic formulations like gels, nanosuspensions, nano-particles, liposomes, microemulsions, iontophoretic dosage forms, and ocuserts were tried and tested in the past few years for ophthalmic delivery. These novel delivery products provide enhanced solubility and bioavailability in a controlled manner to overcome conventional demerits. Here in this review, we have summarized the improvement of drug studies that are currently underway for eye drug carriers, along with stages and important aspects of novel drug delivery to the eye.

One of the primary goals of diabetes management is to maintain blood glucose levels within a normal range, and insulin plays a vital role in achieving this. All Type 1 DM patients and advanced Type 2 DM patients require insulin. Insulin is administered subcutaneously, which may cause patient discomfort from the use of needles. Therefore, developing alternative routes of insulin administration has always been a major focus of diabetes research. This review aims to provide an update on the insulin formulations and delivery routes as well as strategies used to improve its stability and bioavailability for the treatment of diabetes.

Purpose: The goal of the present research was to isolate a biopolymer from Phaseolus vulgaris (P. vulgaris) and Zea mays (Z. mays) plants and used it to construct Resveratrol (RES)-loaded translabial films. Methods: Biopolymers were extracted from P. vulgaris and Z. mays seeds using a simple process. Separated biopolymers, sodium carboxymethylcellulose (SCMC) and tragacanth were subjected to formulation development by incorporating RES-loaded translabial films. The Fourier-transform infrared spectroscopy (FTIR), physical appearance, weight, thickness, folding endurance, swelling index, surface pH, percent moisture absorption, percent moisture loss, vapor transfer rate, and content uniformity of the translabial films were examined. The mucoadhesive, ex-vivo permeation, in vivo and stability studies, were performed. Results: The results showed that RES-loaded translabial films produced from P. vulgaris and Z. mays biopolymers exhibited exceptional mucoadhesive, stability, and permeation properties. Results revealed that the best formulations were prepared from a combination of biopolymer (P. vulgaris C or Z. mays C) with tragacanth. Formulations with tragacanth revealed good swelling and thus permeation profiles. In vivo release of TL 11 was found to be 24.05 ng/ml in 10 hours and it was stable enough at 45°C. Conclusion: This research suggested that RES-loaded translabial formulations can be potentially used for the treatment of Parkinson’s disease with good patient compliance to geriatric and unconscious patients.

Background: Gene therapeutics are being developed to treat metastatic breast tumors, which are mostly resistant to conventional therapies. Targeting platelet-derived growth factor-D (PDGF-D) is a viable approach because it is known to play roles in angiogenesis and tumor growth. The success of gene therapy is largely dependent on delivery vectors, but both viral and nonviral delivery vectors have their disadvantages. Evolving hybrid vectors are being used to overcome those disadvantages. Objectives: In this study, we aimed to prepare a recombinant adenovirus type-5 (Ad5)/chitosan hybrid vector to deliver shPDGF-D in a breast cancer cell line by the noncovalent coating of the Ad5 surface with chitosan, a natural polymer. Methods: The Ad5/chitosan hybrid vector was prepared by the noncovalent coating of the Ad5 surface with different molecular weights (low and high) and different amounts of chitosan (12.5, 25, and 50 μg), and the effect of silencing PDGF-D was investigated in the MDA-MB-231 cell line. Results: In vitro characterization studies showed that the noncovalent chitosan coating increased the size of the Ad5 particle and changed the surface charge from -16.53 mV to slightly neutral. In vitro cell culture studies also showed that the addition of chitosan with both low (73.61%) and high (65.86%) molecular weight increased the PDGF-D silencing efficiency of the Ad5 vector (42.44%) at 48 hours. While low-molecular-weight chitosan had faster effects, high-molecular-weight chitosan provided a more sustained effect in PDGF-D silencing. Conclusion: The results indicate that noncovalent chitosan modification may improve the therapeutic effects of the Ad5 vector, offering the potential for further in vitro and in vivo experiments.

Objective: This study aimed to observe the drug distribution ex-vivo after transdermal drug delivery (TDD) by Shock Wave (SW) and to explore the different effects of the two types of shock waves. Materials and Methods: Nine female Sprague-Dawley (SD) rats were randomly divided into 3 groups: (i) control group; (ii) RESW group (0.35mJ/mm², 2 Hz, 400 pulse); (iii) FESW group (0.16mJ/mm², 2 Hz, 400 pulse). Micro positron emission tomography/computed tomography (PET/CT) was used to observe the distribution of [18]F-NaF. Furthermore, 12 SD rats were randomly divided into 4 groups: (i) control group; (ii) FESW group 1 (0.03mJ/mm², 2 Hz, 400 pulse); (iii) FESW group 2 (0.16mJ/mm², 2 Hz, 400 pulse); (iv) FESW group 3 (0.35mJ/mm², 2 Hz, 400 pulse). High-performance liquid chromatography (HPLC) tested diclofenac sodium and glucose percutaneously TDD by FESW. Statistical significance was conducted by analysis of variance of repeated measurement. Results: The micro PET/CT observed FESW could penetrate [18]F-NaF through the skin, while RESW could not. The second study found the higher the energy of the FESW, the more diclofenac sodium and glucose penetration. Repeated measures analysis of variance found a within-subject effect (diclofenac sodium, F = 4.77, p = 0.03), (glucose, F = 8.95, p = 0.006), significant differences between the control group, FESW group 1, and FESW group 2 (p < 0.05). Conclusion: The study found that FESW can penetrate [18]F-NaF, sugar and diclofenac sodium into the rat body. FESW has a good indication of drug penetration, which provides new biological evidence for route administration.

Aim: The aim of this study was to encapsulate glabridin (GB) into nanoparticles, prepared by an ionic-gelation method blended with chitosan (CS) and poly-γ-glutamic acid (γ-PGA) to address the issue of poor stability and low water solubility of glabridin. Methods: The physicochemical properties of nanoparticles were investigated by transmission electron microscope (TEM), dynamic light scattering (DLS) and fourier-transform infrared (FT-IR) spectroscopy. Results: FT-IR results indicated that the spontaneous interaction between CS, γ-PGA and GB can form a cross linked network-structure, leading to the spontaneous formation of nanoparticles. Morphology of the complex particles was nano-scale spherical shape. Furthermore, particle size was decreased according to the decrease of γ-PGA contents and CS, accompanying with the increase of mixed solution transmittance. The mγ-PGA : mGB = 1: 1 and mCS: (mγ-PGA + mGB) =1: 1 were considered to be a proper preparation condition of CS/γ-PGA/GB hybrid nanoparticles, which produced the smaller nanoparticles with the satisfactory encapsulation efficiency (EE), loading content (LC) and sustained GB release. With the increase of pH values, the potential, EE, and LC decreased gradually, while the particle size increased. The nanoparticles prepared with higher molecular weight γ-PGA had larger particle size and less loading capacity on GB. Additionally, moderate weight ratio of CS/γ-PGA/GB, low pH, and high molecular weight of γ-PGA were favorable for sustained release. Conclusion: It can be concluded that the physicochemical properties of nanoparticles and GB release behaviors were affected by several factors including the weight ratio of CS/γ-PGA/GB, pHvalues, and γ-PGA molecular weight (MW). Nanoencapsulation using CS, γ-PGA and GB has a potential application for the development of functional cosmetic products with skin-whitening effect.

Background: Optimization of MSNs is the most important process for efficient and safe drug delivery systems. Objective: In this study, the physicochemical properties of MSNs were evaluated using various compositions of individual reagents. Methods: MSNs were synthesized according to a modified Stöber method. The physicochemical properties of MSNs were evaluated. Spherical uniform particles were observed in the scanning electron microscope (SEM) and transmission electron microscopy (TEM) image and the meso-structure of MSNs was confirmed. The amorphous and specific hexagonal structure of MSNs was confirmed through Xray diffraction (XRD) and SAXRD. Results: The particle size and surface area according to changes in amounts of reagents ranged from 34.5 ± 2.3 to 216.0 ± 17.1 nm and from 549.79 to 1154.26 m²/g, respectively. A linear relationship was found between the surface area of MSNs and the adsorption rate of methylene blue (MB). MSNs exhibited no apparent cytotoxic effect on Caco-2 cell up to 200 μg/mL. The amounts of tetramethyl ammonium silicate and tetraethyl ortho silicate (TEOS), NaOH, and hexadecyl trimethyl ammonium bromide (CTAB) were adjusted to control the particle size and surface area of MSNs, and it was found that the amounts of synthetic reagents affected the physicochemical properties such as particle size and surface area of MSNs. MSNs with a large surface area adsorbed a large amount of MB. Conclusion: These results indicated that drug adsorption is related to the surface area of MSNs. MSNs did not show cytotoxicity to Caco-2 cells. MSNs may be a promising nanomaterial that could be applied as a carrier for various drugs.