Current Pharmaceutical Biotechnology - Volume 24, Issue 11, 2023

Intervertebral disc degeneration (IDD) is the leading cause of lower back pain and seriously affects the quality of life of patients. The intervertebral disc (IVD) is an environment of hypoxia, ischemia, acidity, and hypertonicity. Matrix acidity potentially negatively affects gene expression, activity, proliferation, and apoptosis of IVD cells. Acid-sensing ion channels (ASICs) are a group of proton-gated ion channels that play important roles in physiological and pathological conditions. The distribution of ASICs in the nucleus pulposus (NP), annulus fibrosus, cartilage endplate, and nucleus pulposus mesenchymal stem cells (NP-MSCs), as well as the special functions of ASIC1a and ASIC3, show that ASICs play an important role in IDD. In this review, we comprehensively discuss the roles of ASICs in the development and basic pathology of IDD and their potential relevance as therapeutic targets. A deeper understanding of the roles of ASICs in these processes may provide novel therapeutic targets for IDD prevention and treatment.

Bacterial engineering modifies bacteria's genomic sequence using genetic engineering tools. These engineered bacteria can produce modified proteins, peptides, nucleic acids, and other biomolecules that can be used to treat various medical conditions. Engineered bacteria can target diseased tissues or organs, detect specific biomarkers in the diseased environment, and even induce specific conditions. Furthermore, a meticulously designed intracellular metabolic pathway can activate or inhibit the expression of related genes, synthesise biologically active therapeutic molecules, and precisely deliver drug payloads to diseased tissues or organs. Lactococcus (L. lactis), Salmonella (S. typhi), and E. coli (E. coli Nissle) are the most studied engineered microorganisms used as drug carriers. These have been used in vaccines to treat multifactorial diseases such as cancer, autoimmune diseases, metabolic diseases, and inflammatory conditions. Other promising strains include Bifidobacterium animalis, Listeria monocytogenes, Staphylococcus epidermidis, Staphylococcus lugdunensis, and Clostridium sporogenes. Despite the low reported risk, toxic effects associated with bacterial cells, limiting their efficacy and rapid clearance due to immune responses stimulated by high bacterial concentrations, remain major drawbacks. As a result, a better and more effective method of drug delivery must be developed by combining bacterial-based therapies with other available treatments, and more research in this area is also needed.

Cancer patients frequently report experiencing pain as one of their symptoms. Cancerrelated pain is often caused by the tumor itself, especially when the tumor is pressing on nerves. In addition to the pain caused by the tumor itself, patients also experience discomfort from the treatment, such as surgery, chemotherapy, radiation therapy, and the diagnostic procedures. The majority of today's pain therapies rely on opioid analgesics, which have not been shown to be effective. The adverse effects of opioids and their addictive properties call for the development of innovative treatment techniques. Nanotechnology offers answers to the issues raised above, which are related to the utilization of more conventional modes of therapy. These nanotechnology-based nanotherapeutics reduce the systemic toxicity, offering outstanding selectiveness and prolonged release of the analgesic drugs at the target site. Thus, these reduce cancer-induced pain in the patients. In this article, we will explain the mechanism behind the most common types of pain that are caused by cancer, including neuropathic, somatic, and visceral pain. In addition, a comprehensive discussion is held on the use of various nanotherapeutics as analgesic drug carriers, as well as on their impacts and the potential opportunities that lie ahead in the field of cancer pain treatment.

Background: Drug resistance is a current issue affecting parasites caused by Plasmodium. Therefore, researchers have expanded their studies on nanoparticles to find new and effective drugs that can treat drug-resistant strains. The present study systematically investigates the effect of different nanoparticles, including metal, polymer, and lipid nanoparticles, on Plasmodium berghei. Methods: In this study, English-language online literature was obtained from the databases Science Direct, PubMed, Scopus, Ovid, and Cochrane to conduct a systematic review. In the search, we used the keywords: (Plasmodium Berghei) AND (Malaria) AND (Parasitemia) AND (antimalarial activity) AND (nanoparticles) AND (Solid lipid NPS) AND (Nano lipid carriers) AND (Artemether) AND (Chloroquine) AND (intraperitoneal) AND (in vivo). Initially, a total of 160 studies were retrieved from the search. After removing duplicates, 80 studies remained. After reviewing the title and abstract of each study, 45 unrelated studies were eliminated. Results: The remaining 35 studies were thoroughly reviewed using the full texts. The final result was 21 studies that met the inclusion/exclusion criteria. Conclusion: Using these findings, we can conclude that various nanoparticles possess antiparasitic effects that may be applied to emerging and drug-resistant parasites. Together, these findings suggest that nanostructures may be used to design antiparasitic drugs that are effective against Plasmodium berghei.

Psoriasis has been considered as a chronic inflammatory skin disease which leads to the dysfunction of immune systems. According to the World Psoriasis Day consortium, psoriasis affects around 125 million individuals globally or about 2% to 3% of the overall population. Most of the conventional drug delivery systems primarily attempt to relieve symptoms of psoriasis and are ineffective in providing targeted action and higher bioavailability because of the drug's short half-life and instability, as well as they lack safety and efficacy. The shortcomings of conventional drug delivery systems give rise to the development of novel drug delivery systems which includes liposomes, transferosomes, ethosomes, niosomes, emulsomes, dendrimers, hydrogel, nanoparticles, etc. These novel formulations may enhance the therapeutic effects by changing physiological and pharmacokinetic parameters. Several research reports suggest that these novel drug delivery systems may enhance therapeutic effects which can be used as a promising approach for the treatment of psoriasis. The liposomes based drug delivery system have been considered as most promising vehicles for enhancing therapeutic potentials of drugs into or through the skin upon topical application. Liposomes have small unilamellar vesicles which may enhance the penetration ability through stratum corneum layer of skin. Therefore, present review article highlights on the different aspects of the liposomes as potential drug delivery system for the treatment of psoriasis.

Background: Nanoparticle formulations development for anti-aging treatment is increasing due to their multifunctional properties. These nanotechnological strategies can target cellular/ molecular pathways of the skin affected by the aging process. However, a review of these strategies is required to discuss their efficacy/safety and establish the needs for further research. Objective: Innovative nanotechnological advances for skin anti-aging/rejuvenation are summarized and discussed in this work. Methods: The information in this review was extracted from recent and relevant studies using nanotechnology for anti-aging treatment from scientific databases. Results and Discussion: Results show an enhanced skin anti-aging effect of actives-loaded nanoparticles of next generation (nanostructured lipid carriers, fullerenes, transfersomes, protransfersomes, niosomes, ethosomes, transethosomes, glycerosomes, phytosomes) compared with nanocarriers of first generation or conventional formulations. Anti-aging active ingredients such as, flavonoids (rutin, hesperidin, quercetagetine, quercetin, epigallocatechin-3-gallate, myricetin, silibinin, curcuminoids, isoflavones); vitamins (E, D3, CoQ10); acids (hyaluronic, ascorbic, rosmarinic, gallic); extracts (Citrus sinensis, Tagetes erecta L., Achillea millefolium L., Citrus aurantium L., Glycyrrhiza glabra L., Aloe vera, propolis earned by Apis mellifera); and other compounds (adenosine, beta-glucan, heptapetide DEETGEF, resveratrol, cycloastragenol, melatonin, botulinum toxin, grapeseed oil), have been successfully entrapped into nanoparticles for skin rejuvenation. This encapsulation has improved their solubility, bioavailability, stability, permeability, and effectivity for skin anti-aging, providing a controlled drug release with minimized side effects. Conclusion: Recent studies show a trend of anti-aging herbal active ingredients-loaded nanoparticles, enhancing the moisturizing, antioxidant, regenerating and photoprotective activity of the skin. Suitable safety/shelf-life stability of these novel formulations is key to a successful translation to the clinic/industry.

World Health Organization has reported an estimated 1.5 million deaths directly due to diabetes in 2019. Center for Disease Control and Prevention, in its National Diabetes Statistics Report, 2020, says that 1 in 10 United States residents has diabetes. This rapid progression of diabetes is noteworthy despite significant advances in the field of antidiabetic medicine. The critical challenges in treatment are dyslipidemia, hyperinsulinemia, and hyperglycemia. The latest research has also linked diabetes to carcinogenesis. The diabetic condition accelerates cell growth, proliferation, migration, inflammation, angiogenesis, metastasis, and inhibition of apoptosis in cancer cells. In addition, diabetic complications of nephropathy, retinopathy, neuropathy, cardiomyopathy, peripheral arterial disease, coronary artery disease, and stroke increase morbidity. Amidst all these challenges, a ray of hope is the advent of nanocarriers. The nano size helps in the targeted and controlled delivery of drugs. In addition, nanocarrier formulation helps in the delivery of acid-labile and enzyme- labile molecules and plant-based macromolecules via the oral route. Its use in the form of dendrimers, ethosomes, niosomes, transfersomes, and polymeric nanoparticles is established. In addition, different polymers used to formulate nanocarriers are also established for targeting diabetes. Thus, this review aims to compile approaches involving the use of nanocarriers for the betterment of pharmacotherapy of diabetes and to provide a way ahead for researchers in the field.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly known as COVID-19, created rack and ruin and erupted as a global epidemic. Nearly 482.3 million cases and approximately 6.1 million deaths have been reported. The World Health Organization (WHO) designated it an international medical emergency on January 30, 2020; shortly in March 2020, it was declared a pandemic. To address this situation, governments and scientists around the globe were urged to combat and prevent its spread, mainly when no treatment was available. Presently, quantitative real-time polymerase chain reaction (qRT-PCR) is the most widely utilized technique for diagnosing SARS-CoV-2. But this method is cumbersome, tedious, and might not be quickly accessible in isolated areas with a circumscribed budget. Therefore, there is a quest for novel diagnostic techniques which can diagnose the disease in a lesser time in an economical way. This paper outlines the potential of biosensors in the diagnosis of SARS-CoV-2. This review highlights the current state of presently available detection techniques, expected potential limits, and the benefits of biosensor-implicated tests against SARS-Cov-2 diagnosis. CRISPR-Cas9 implanted paper strip, field-effect transistor (FET) implanted sensor, nucleic-acid centric, aptamers-implanted biosensor, antigen-Au/Ag nanoparticles-based electrochemical biosensor, surface-enhanced Raman scattering (SERS)-based biosensor, Surface Plasmon Resonance, potential electrochemical biosensor, optical biosensor, as well as artificial intelligence (AI) are some of the novel biosensing devices that are being utilized in the prognosis of coronaviruses.

Berberine (BBR) is an isoquinoline alkaloid with several therapeutic properties, including anti-microbial, anti-diarrhea, anti-viral, anti-inflammatory, antihypertensive, anti-tumor, and anti-diabetes. However, its low water solubility, low absorption, first-pass metabolism, nontargeting, and poor bioavailability represent major hurdles to its successful therapeutic applications. Hence, researchers have attempted to enhance the biological and pharmacological activity of BBR to overcome its drawbacks by encapsulation of BBR in micro and nano delivery systems. For the preparation of nanostructured carrier systems of BBR, a range of methods has been developed, and each method has its benefits and characteristics. This review critically describes different types of nanocarriers like liposomes, niosomes, ethosomes, nanoemulsions, polymeric nanoparticles, micelles, dendrimers, and silver and gold nanoparticles that have been used for encapsulation of BBR for different therapeutic applications. The various pharmaceutical characteristics (size, shape, entrapment efficiency, zeta potential, drug release, and drug permeation) of these BBR-loaded nanocarriers have been discussed systematically. Preclinical studies of BBR nanoformulations involving animal models are also discussed.

Background: Annona muricata L. (Annonaceae) (AM)'s remarkable anti-inflammatory and anti-cancer activities make it a targeted plant to be explored for its immunomodulatory properties. Traditional practitioners have employed various components of AM to cure a variety of ailments, including cancer, diabetes, and inflammation. Objective: The present study evaluated the immunosuppressive effects of 80% ethanol extract of of AM leaves in male Wistar rats on different parameters of humoral and cellular immune responses. Methods: AM leaf extract (AMLE) was analyzed using UHPLC-MS/MS to profile its secondary metabolites. AMLE was rich in polyphenols which include (epi)catechin-(epi)catechin-(epi) catechin, caffeic acid, coumaroylquinic acid, hyperin, kaempferol, quinic acid and rutin. The rats were administered 100, 200 and 400 mg/kg bw of the extract daily for 14 days. The effects of AMLE on innate immune responses were determined by evaluating phagocytosis, neutrophils migration, reactive oxygen species (ROS) release, CD11b/CD18 integrin expression, and ceruloplasmin, lysozyme and myeloperoxidase (MPO) levels. The adaptive immune parameters were evaluated by immunizing the rats with sheep red blood cells (sRBC) on day 0 and administered orally with AMLE for 14 days. Results: AMLE established significant immunosuppressive effects on the innate immune parameters by inhibiting the neutrophil migration, ROS production, phagocytic activity and expression of CD11b/CD18 integrin in a dose-dependent pattern. AMLE also suppressed ceruloplasmin, MPO and lysozyme expressions in the rat plasma dose-dependently. AMLE dose-dependently inhibited T and B lymphocytes proliferation, Th1 and Th2 cytokine production, CD4⁺ and CD8⁺ co-expression in splenocytes, immunoglobulins (IgM and IgG) expression and the sRBC-induced swelling rate of rat paw in delayed-type hypersensitivity (DTH). Conclusion: The strong inhibitory effects on the different parameters of humoral and cellular responses indicate that AMLE has potential to be an important source of effective immunosuppressive agents.