Current Pharmaceutical Design - Volume 28, Issue 8, 2022

Microsponges delivery systems (MDS) are highly porous, cross-linked polymeric systems that activate due to temperature, pH, or when rubbed. MDS offer a wide range of advantages, like controlled drug release, site-specific action, stability over a broad range of pH, less irritation, cost-effectiveness, and improved patient compliance. They can be transformed into various dosage forms like creams, gels, and lotions. MDS are suitable for the treatment of topical disorders like acne, psoriasis, dandruff, eczema, scleroderma, hair loss, skin cancer, and other dreadful diseases. The applications of MDS in drug delivery are not limited to topical drug delivery but are also explored for oral, parenteral, and pulmonary drug deliveries. Microsponges have been studied for colon targeting of drugs and genes. Additionally, MDS have several applications such as sunscreen, cosmetics, and over-the-counter (OTC) products. Furthermore, MDS do not actuate any irritation, genotoxicity, immunogenicity, or cytotoxicity. Therefore, this review extensively highlights microsponges, their advantages, key factors affecting their characteristics, their therapeutic applications in topical disorders and in cancer, their use as cosmetics, as well as recent advances in MDS and the associated challenges.

Hydrogels for the modified-release drug delivery systems are a continuously growing area of interest for the pharmaceutical industry. According to the global market, the profit resulting from the use of polymers in this area is projected to reach $31.4 million by 2027. This review discusses the recent advances in and perspectives of hydrogel in drug delivery systems for oral, parenteral, nasal, topical, and ophthalmic delivery. The search was conducted, in January 2021, in an extensive database to identify studies published from January 2010 to December 2020. We described the main characteristic of the polymers to obtain an ideal hydrogel for a specific route of administration and the formulations. It was concluded that the hydrogels are useful to decrease the number of doses and side effects, promote adhesion of patient, and enhance the bioavailability of the drugs, thus improving the safety and efficacy of the treatment.

The transport of drugs to the central nervous system is the most challenging task for conventional drug delivery systems. The reduced permeability of drugs through the blood-brain barrier is a major hurdle in delivering drugs to the brain. Hence, various strategies for improving drug delivery through the blood-brain barrier are being explored. Novel drug delivery systems (NDDS) offer several advantages, including high chemical and biological stability, suitability for both hydrophobic and hydrophilic drugs, and can be administered through different routes. Furthermore, the conjugation of suitable ligands with these carriers tends to potentiate targeting to the endothelium of the brain and could facilitate the internalization of drugs through endocytosis. Further, the intranasal route has also shown potential, as a promising alternate route, for the delivery of drugs to the brain. This can deliver the drugs directly to the brain through the olfactory pathway. In recent years, several advancements have been made to target and overcome the barriers of the brain. This article deals with a detailed overview of the diverse strategies and delivery systems to overcome the barriers of the brain for effective delivery of drugs.

Many of the synthetic and herbal drugs, despite their notable in vitro findings, demonstrate insignificant in vivo activity, the majority of the time due to poor bioavailability. As per Biopharmaceutical Classification System (BCS), one of the main concerns is low solubility and/or permeation of drugs resulting in reduced absorption and poor bioavailability. To overcome these issues, various strategies have been adopted, including the use of permeation enhancers which are also known as bioenhancers. Bioenhancers are synthetic or natural compounds that increase the bioavailability of drugs and nutrients such as vitamins, amino acids, minerals, etc., into the systemic circulation and at the site of action for exhibiting improved therapeutic action. By improving bioavailability, bioenhancers can reduce drug dose, decrease the treatment period, and circumvent the problem of drug resistance. Although numerous studies have reported the application of synthetic bioenhancers, plant based bioenhancers can serve as a better alternative owing to their natural origin. Literature reviews have revealed that plant-based bioenhancers have been used in a wide variety of antibiotics, antiviral, and anti-cancer therapeutics. These can be categorized based on their sources and mechanism of action. This review will provide a systematic and detailed overview of the various plant based bioenhancers and their applications.

Background: Gastric ulcer has been a major cause of morbidity and mortality worldwide, and it has been linked to factors such as nutritional deficiency, smoking, stress, and continuous intake of non-steroidal antiinflammatory drugs (NSAIDs). The search for new anti-ulcer therapeutic agents has been the subject of several studies. Recently, the gastroprotective effect of Celtis iguanaea has been reported, with linoleic acid (LA) responsible for many of the therapeutic effects of this medicinal plant. Aims: This study aims to investigate the gastroprotective activity and the possible mechanisms in which LA may be involved through different experimental assays in mice. Methods: The gastroprotective activity of LA was evaluated in the ulcer induced by indomethacin, HCl/EtOH, hypothermic-restraint stress and pyloric ligation. For the investigation of gastroprotective mechanisms, the quantification of the volume (mL), pH and total acidity of gastric secretion were considered. Results: The oral administrations of 25 mg/kg, 50 mg/kg or 100 mg/kg of body weight of LA were capable of protecting the gastric mucosa against HCl/ethanol (10 mL/kg p.o.), and oral/intraduodenal treatment administrations of 50 mg/kg LA showed protection from ulcers induced by indomethacin, hypothermic-restraint stress and pyloric ligation. Conclusion: The results of this study show the gastroprotective role of LA in gastric mucosal damage induced by all assayed distresses. The observed gastroprotection possibly occurs due to the mediated increase of mucosal defensive factors.

Background: S-Allylcysteine (SAC), an organosulfur phytochemical sourced from aged garlic extract, is well known for its varied biomedical applications, such as anti-oxidant, anti-inflammatory, and detoxification mechanisms. Despite this, the scientific findings on the defensive impact of SAC against kidney failure (KF) are still unclear. Therefore, in the current investigation, the animal model of KF was induced by adenine in Wistar rats, and the animals were divided into four groups as control, KF induction using adenine, SAC treated KF rats for an experimental duration of 8 weeks. Methods: KF progression was assessed by various serum and tissue markers, and the results demonstrated that the renal functions’ markers, KIM-1 (kidney injury molecule-1), cystatin, NGAL (neutrophil gelatinase-associated lipocalin), were found increased in adenine-treated rats compared to control. In addition, the inflammatory markers, matrix proteins, and fibrosis signatures explicated by RT-PCR, ELISA demonstrated a profound increase. On the other hand, rats received SAC mitigated KF considerably (p < 0.001) with restored cellular functions. Besides, SAC pre-treatment abrogated the cytokines and pro-inflammatory signals (COX-2 and PGE2) in a dose-dependent manner. Conclusion: Furthermore, the fibrosis signaling markers mediators, such as SMAD-2,-3 were increased with associated matrix proteins. Thus, the present study substantiated that SAC possesses a significant renoprotective effect that might have been demonstrated by the inhibition of the TGF-β1/Smad3 signaling pathway.

Background: It is widely recognized that atherosclerosis (AS) is related to vascular inflammation. Panax notoginseng saponins (PNS) extracted from the roots of Panax notoginseng have been shown to possess anti-inflammatory activity. It is widely used in the clinical treatment of cardiovascular and cerebrovascular diseases, but the protective effect of PNS on atherosclerosis is not fully understood. This study was designed to test the effects of PNS administration in apolipoprotein (apo)-E-deficient (ApoE-/-) mice on the activation of NF-ΚB p65, IL-1β, IL-6, TNF-α and Calpain1 proteins. Methods: 24 ApoE-/- mice fed with high-fat diet for 8 weeks to create the AS model. PNS, dissolved in three distilled water, was administered orally to two treatment groups at dosages of 60 mg/kg/d/mice and 180 mg/kg/d/mice. After 8 weeks, peripheral blood was collected for assessing the levels of TG, TC, LDL-C and HDL-C in serum by Biochemical Analyzer. HE staining was used to observe pathomorphological changes in the aortic root. Oil Red O staining was used to observe the lipid deposition in the aortic root. ELISA kits were used to assess the levels of IL-1β and TNF-α in serum. The expression levels of NF-ΚB p65, IL-1β, IL-6, TNF-α, and Calpain1 proteins in the aortic root were identified by Western blot. Results: After PNS administration for 8 weeks, the levels of TG, TC, LDL-C, IL-1β and TNF-α were decreased, the level of HDL-C was increased in apoE-/- mice. The arrangement of the tissue of aortic root tended to be normal, the cell morphology was restored, and the lipid depositions were reduced in apoE-/- mice treated with PNS. Moreover, PNS inhibited the expression levels of NF-ΚB p65, IL-6, IL-1β, TNF-α and Calpain1 proteins of aortic root tissues in apoE-/- mice. Conclusion: PNS may inhibit the progression of atherosclerotic lesions via their anti-inflammatory biological property. PNS suppress the NF-ΚB signaling pathway and inhibits the expression of pro-inflammatory factors such as NF-ΚB p65, IL-6, IL-1β, TNF-α and Calpain1 proteins in aortic root tissues of apoE-/- mice.