Current Drug Delivery - Volume 20, Issue 5, 2023

Oral candidiasis is an opportunistic infection of the oral mucosa sustained by fungi of the genus Candida. Various Candida species, with a predominance of C. albicans, normally a saprophyte of the oral cavity, may become virulent and infect the oral mucosa with variegated clinical presentation, in case of imbalance of the oral microbiota, the presence of local predisposing factors and systemic conditions that weaken the immune system. Conventionally, oral candidiasis eradication is done with the help of antifungal drugs. However, the growing phenomena of drug resistance and the increase in infections sustained by non-albicans species being less responsive to common antifungals have orientied researches towards the experimentation of alternative therapies. The present review considered the most promising alternative therapeutic proposals. The use of plant derivatives with phytotherapy is a promising option, such as probiotics, to rebalance the oral microbiota in case of dysbiosis. Finally, antimicrobial photodynamic therapy (aPDT), with highly selective fungicidal activity and free of side effects, is also being studied as a powerful alternative to drug administration. All these therapies are alternatives or supportive to the conventional treatment of recurrent and non-drug-responsive forms of oral candidiasis. However, further studies are needed to define the most active compounds, the efficacy of the therapies compared with the conventional ones, and the planning of regulated and standardized protocols.

Solid tumor is one of the highly prevalent cancers among humans and the treatment is often restricted by drug resistance to chemotherapeutics. One of the main reasons might be attributed to the limited penetration ability of drugs through tumor tissues due to heterogeneity within the tumor microenvironment. Over the recent years, so much research has been carried out for developing phytochemicals as cancer therapeutic agents. These are well-established as potential candidates for preventing and treating cancer, especially solid tumors, but have limited clinical applications due to their large molecular size, low bioavailability, stability, and target specificity, along with other side effects when used at high concentrations. There has been a widely proposed nano delivery system of bioactive constituents to overcome these obstacles. This nanostructured system might be able to potentiate the action of plant constituents, by reducing the side effects at a lesser dose with improved efficacy. Indeed, nanosystems can deliver the bioactive constituents at a specific site in the desired concentration and avoid undesired drug exposure to normal tissues. Furthermore, these nanoparticles demonstrate high differential absorption efficiency in the target cells over normal cells by preventing them from interacting prematurely with the biological environment, enhancing the cellular uptake and retention effect in disease tissues, while decreasing the toxicity. This review discusses various treatment stratagems used for the management of solid tumors with special emphasis on nanocarrier systems as a potential treatment strategy for herbal drugs. This also covers a wide list of plants that are used for the treatment of solid tumors and cancers along with their mechanisms of action and enlists various nanocarrier systems used for different phytoconstituents. This review gives a brief idea about different plants and their constituents exploited for their anticancer/antitumor potential along with several nanocarrier systems employed for the same and gives future directions to stress the nanotechnology platform as a valuable approach for the prevention and treatment of solid tumors.

Background: Chemotherapy for stomach cancer often includes several side effects. The primary reasons for the failure of such treatment approaches are low drug concentrations in target tissues and a short stomach residence time. Objective: Gastroretentive controlled drug delivery systems improves the therapeutic performance of chemotherapeutic drugs following oral administration because of the longer gastric retention time. The goal of this study was to find suitable gastroretentive formulations that might be used for the localized treatment of stomach cancer. Methods: The purpose of this study is to summarize current advances in gastro-retentive drug administration for oral chemotherapy, with a focus on floating, mucoadhesive, and swellable systems. This article also discusses the potentials and limitations of existing gastroretentive drug delivery systems used in cancer chemotherapy. Results: Due to increased stomach retention and modified drug release properties, gastroretentive controlled drug delivery systems improve the therapeutic performance of anti-cancer drugs used to treat stomach cancer. Conclusion: Gastroretentive drug delivery systems appear to be a promising carrier for localized chemotherapy with smaller doses and better patient compliance. However, selection of drug candidates, drugfood interactions and chemotherapy-induced gastric discomfort remain the key characteristics that must be addressed to improve treatment outcomes.

An oral route for drug administration is a more suitable route because of its ease of administration, pain avoidance, patient compliance, accommodation of various types of drug molecules, etc. But there are many factors affecting the oral absorption of the drugs. The main factor associated with oral absorption is drug solubility. Many new chemical molecules are poorly soluble in nature and can be included in BCS classes II and IV. For the administration of these drugs through the oral route, it was found that solubility is the rate limiting step. The low solubility of these drugs tends to cause precipitation in the gastrointestinaltract (GIT), affecting their bioavailability. Drug precipitation may be triggered by many factors such as insolubility of the drug in co-solvent, drug-excipient interactions, physiochemical properties of the drug, sudden change in the pH of the environment, incompatibility with the surfactant, etc. Precipitation of a drug may occur in two stages, formation of nucleation and crystal growth. To overcome precipitation, there are many strategies such as the use of polymers, the addition of surfactants, modulating drug loading and solubilizing capacity, change in the pH of the environment, etc. In this review, the causes of precipitation and diverse strategies of precipitation inhibition are critically reviewed.

Most of the new drug candidates and present ones are lipophilic, which leads to low bioavailability. Self-emulsifying drug delivery systems (SEDDS) have emerged as promising formulation system for poorly water-soluble drug candidates. Over the last two decades, various such drug compounds were used by researchers for the development of SEDDS. At present, many SEDDS formulations are also available in the market. Though SEDDS offer many advantages but drawbacks like low drug loading, few dosage form choices, difficulty in handling and storage led to the solidification of this system by various methods. Solidification by spray drying technique offers a lot of advantages like scalability and stability. This particular method is the focus of this review. Adsorbent carriers have the most significant role in the fate of this formulation and its compatibility with the drug candidate. This review addresses the advantages, method of development, spray drying specifications, and characterization of S-SEDDS in detail. Furthermore, the prospect of turning spray-dried SEDDS into tablets by punching which offers potential advantages of increased bioavailability and stability has also been discussed.

Objective: The main focus of this article is to analyze numerous in-vitro methods and their modifications currently used to assess the absorption or permeability of drug molecules from different formulations. Methods: In the literature, no single method can be applied as a gold standard for measuring the exact permeability of each drug molecule. Various in-vitro methods, including tissue and cell-based models, are reported to assess the absorption of drugs. Caco2 cell is a widely used model for absorption studies but sometimes provides inaccurate results. Alternative methods like Madin-Darby canine kidney, IEC- 18, TC-7, 2/4/A1, and IPEC-J2 cell lines are also used. In this study, the merits and demerits of each method have been described, along with the factors affecting the results of absorption studies. The selection of an appropriate method is critical in accurately assessing the permeability and absorption of drugs by mechanisms like vesicular and active transport. This review article aims to provide in-depth knowledge regarding the different in-vitro methods, strategies, and selection of appropriate in-vitro models to predict intestinal absorption. Conclusion: A flow chart diagram for decision-making in selecting an appropriate in-vitro permeability model for formulation has been proposed for estimating permeability.

Advancement in nanotechnology leads to the development of polysaccharides which are very efficient carriers in delivering therapeutic substances like drugs, proteins, and genes. This review describes the role of polysaccharides and their derivatives in the cellular targeting of genetic materials for the treatment of various biological disorders. Applications, challenges, advantages, and disadvantages of polysaccharides used in gene delivery are discussed in the manuscript. Cationic and natural polysaccharides are generally used for RNA and DNA delivery and exhibit better performance in gene transfection. After a substantial literature survey, it can be concluded that different polysaccharides and their derivatives are effectively used in the delivery of genetic material. Natural polysaccharides are widely used due to their advantageous properties like biocompatibility, biodegradability, and low toxicity in the biological environment.

Introduction: Overuse and improper dosage of antibiotics have generated antimicrobial resistance (AMR) worldwide. Pseudomonas aeruginosa (PA), a well-known bacterial strain can establish MDR leading to a variety of infections in humans. Furthermore, these PA strains hold the ability to form biofilms by generating extracellular polymeric substances on the surface of medical tools and critical care units. To supersede the infectious effect of MDR organisms, silver nanoparticles have been known to be the choice. Materials and Methods: Hence, the present study concentrates on the engineering of varying concentrations of gelatin-based polymeric hydrogel embedded with silver nanoparticles (G-AgNPs) for controlled bactericidal activity against MDR PA biofilms. Biofilms formation by MDR PA was confirmed microscopically and spectroscopy was taken as a tool to characterize and analyze the efficacy at every stage of experiments. Results: When MDR PA biofilms were treated with G-AgNPs prepared with 5 % gelatin concentration (AgNP3), they exhibited superior bactericidal activity. Furthermore, a dose-dependent study showed that 800 nM of AgNP3 could inhibit the growth of MDR PA. Conclusion: Hence it can be concluded that silver nanoparticles synthesized in the presence of 5% gelatin can act as a bactericidal agent in the inactivation of MDR PA biofilms, thereby controlling the infections caused by these biofilms.

Background: Colorectal cancer is one of the most serious gastrointestinal cancers in Africa and its prevention is a pronounced challenge in contemporary medicine worldwide. Objective: The present study aimed to develop nanoemulsion drug delivery system using pomegranate polysaccharides (PGPs) as an alternative cancer remedy, and then the evaluated its biological activities. Methods: The PGPs yield and chemical composition were evaluated, and then a PGPs nanoemulsion (PGPs-NE) was prepared using the self-emulsification technique with an oil phase. The physicochemical characterization of PGPs-NE was then analyzed. The in vitro antioxidant, anti-inflammatory activities, and antitumor potency of PGPs and PGPs-NE were also evaluated. Results: The PGPs yield was 10%. The total sugar and protein content of PGPs was 44.66 mg/dl and 19.83μg/ml, respectively. PGPs were mainly composed of five monosaccharides including fructose, glucose, galactose, rhamnose, and arabinose. Concerning physiochemical characterization, the formulated PGPs-NE had three optical absorption bands at 202, 204, and 207nm and a transmittance of 80%. Its average hydrodynamic particle size was 9.5nm, with a PDI of less than 0.2 and a negative zeta potential (-30.6 mV). The spherical shape of PGPs-NE was confirmed by a transmission electron microscope study, with an average size of less than 50 nm. Additionally, the method used to prepare the PGPs-NE formulation provided high entrapment efficiency (92.82%). The current study disclosed that PGPs-NE exhibited strong antioxidant, anti-inflammatory, and antitumor agent potency compared to that of free PGPs. Conclusion: These promising current findings provide evidence for the possible efficacy of novel PGPs-NE as an alternative treatment for CRC.

Background: Carbamazepine (Cbz) is the first-line drug for epileptic seizures but exhibits fluctuation at the plasma level and side effects after oral administration.To overcome these problems, Cbz should be targeted directly into the brain. Therefore, the current experimental design was aimed to formulate and optimize the Cbz containing solid lipid nanoparticles (SLNs) for brain delivery via intranasal administration to get rid of oral complications associated with Cbz. Methods: A full factorial design was performed to evaluate the effect of variables (X1 lipid concentration, X2 surfactant concentration, and X3 sonication time) on the response variables (size of nanoparticles, entrapment efficiency, and drug release). A two-level, three-factor design was employed herewith, and eight formulations were developed. Further, the formation of Cbz containing SLNs was characterized by compatibility, particle size, entrapment efficiency, and drug release with the support of Fourier Transform Infra-Red (FTIR), Zeta sizer, Transmission Electron Microscopy (TEM), Ultra-violet (U.V.), and High-Performance Liquid Chromatography (HPLC). Results: All eight formulations were characterized through particle size, entrapment efficiency, and invitro drug release performance. Out of eight characterized formulations, SN1 showed the most promising results, including particle size of 210 ± 2.14 nm, entrapment efficiency of 42.1 ± 1.09%, and drug release of 61.3 ± 2.02% and considered an optimized batch. Additionally, the optimized batch SN1was further evaluated for an in-vivo study on male Wistar Rats. Conclusion: The study revealed that a high amount of drug was reached into the brain through intranasal administration compared to the intravenous route. Therefore, it can minimize the unwanted side effects of the Cbz associated with oral administration. The formulation SN1 possesses an excellent drug targeting efficiency of 3.014. Finally, the current experimental work concluded that there is a direct pathway from the intranasal route to the brain. This delivery system can be beneficial for directly delivering CNS-active drugs into the brain.

Background: Pelargonium graveolens L'Hér has traditionally been used to reduce skin inflammation, and recent studies have confirmed antioxidant compounds in the plant's extract. The present study aimed to prepare a lipogel formulation from P. graveolens hydroalcoholic extract and evaluate its efficacy on the wound healing process in an animal model. Material and Methods: The aerial part extract of P. graveolens was prepared through percolation. Additionally, plastibase was prepared by mixing 5% of low-molecular-weight polyethylene with hot mineral oil (130°C). The extract (5%) was levigated in the mineral oil (5-15%) and dispersed in the cooled plastibase. The physical properties of the lipogel, thermal stability, and microbial limits were tested. Further, the effect of the lipogel in the wound healing rate was examined among male Wistar rats, and skin tissue samples were assessed histologically. Results and Discussion: The results represented the best rheological and thermal stability characteristics in the formulation with 5% mineral oil (as the levigator). The lipogel-treated group had the least burn area compared to the silver sulfadiazine and negative control groups (p<0.05). The microscopic examination of tissue samples revealed increased collagen fiber production and maturation and significantly also faster epithelial repair among lipogel-treated rats than in the other two groups(p<0.05). Conclusion: The results indicated the significant therapeutic effects of P. graveolens lipogelon burn healing. The suitable physicochemical properties and the low lipogel production cost facilitate further scale-up studies.

Objective: Silver sulfadiazine has often been used as a topical antibacterial agent for burn wounds. Aim of this study is to develop silver sulfadiazine-loaded microsponge along with honeyimpelled hydrogel for improved burn wound healing activity. Methods: Microsponge were prepared by quasi-emulsion solvent diffusion method. Formulation variables such as concentration of emulsifier and Internal phase volume were optimized by using 3² factorial design. Further, SSD microsponge-based Hydrogel was prepared using carbopol 934 and honey as natural healing agents. In vitro drug release, ex vivo drug deposition, skin irritancy study, and in vivo antibacterial activity were evaluated for optimized hydrogel formulations. The MTT assay was used to determine the safety of the optimized hydrogel using epidermal keratinocyte (HaCaT) cell lines. Results: At the 12th hour, in vitro drug release was found to be 85.11±0.89. An adjusted microspongeloaded hydrogel increased medication retention ability in the epidermal layers when compared to the commercial product. There was also less application time, no skin irritation, low cytotoxicity on dermal cell lines, and better wound contraction. Conclusion: The prepared microsponge-loaded hydrogel can serve as a potential alternative for burn wound as compared to the marketed product.

Background: Reverse cholesterol transportation is essential for high-density lipoprotein (HDL) particles to reduce the cholesterol burden of peripheral cells. Studies have shown that particle size plays a crucial role in the cholesterol efflux capacity of HDLs, and the reconstituted HDLs (rHDLs) possess a similar function to natural ones. Objective: The study aimed to investigate the effect of particle size on the cholesterol efflux capacity of discoidal rHDLs and whether drug loadings may have an influence on this effect. Methods: Different-sized simvastatin-loaded discoidal rHDLs (ST-d-rHDLs) resembling nascent HDL were prepared by optimizing key factors related to the sodium cholate of film dispersion-sodium cholate dialysis method with a single controlling factor. Their physicochemical properties, such as particle size, zeta potential, and morphology in vitro, were characterized, and their capacity of cellular cholesterol efflux in foam cells was evaluated. Results: We successfully constructed discoidal ST-d-rHDLs with different sizes (13.4 ± 1.4 nm, 36.6 ± 2.6 nm, and 68.6 ± 3.8 nm) with over 80% of encapsulation efficiency and sustained drug release. Among them, the small-sized ST-d-rHDL showed the strongest cholesterol efflux capacity and inhibitory effect on intracellular lipid deposition in foam cells. In addition, the results showed that the loaded drug did not compromise the cellular cholesterol efflux capacity of different-sized ST-d-rHDL. Conclusion: Compared to the larger-sized ST-d-rHDLs, the small-sized ST-d-rHDL possessed enhanced cellular cholesterol efflux capacity similar to drug-free one, and the effect of particle size on cholesterol efflux was not influenced by the drug loading.