RSC Pharmaceutics最新文献

Osteoarthritis (OA) is a chronic degenerative condition characterized by the wearing down of the articulating surfaces of the tibia–femoral joint. It involves the breakdown of cartilage, leading to a reduction in joint space, primarily affecting the medial aspect of the joint. Treatment options for OA include oral and topical medications, as well as chemical and surgical interventions. Among potential treatments, naproxen (NAP) and gaultheria oil (GO) have shown promising anti-inflammatory effects. However, NAP's distribution is hindered by its limited solubility and poor penetration. Additionally, there is no marketed product or published report of any combination product of GO with any synthetic drug. Hence a novel nanoemulsion (NE) based gel has been developed. For NE development, Tween 80 and PEG 400 were selected as the surfactant and co-surfactant, respectively. The particle size, polydispersity index (PDI) and zeta potential were found to be 209.2 nm, 0.2119, and −24.7 mV respectively. In vitro cumulative drug release in the initial 24 h was 95.64 ± 0.75% for NE and 87.44 ± 0.84% for NEG. Similarly, in vitro drug permeation after 24 h was 17.447 μg cm⁻² and 9.3287 μg cm⁻², respectively. The rheological behavior, skin irritation, and stability of the NEG were also evaluated.

To ensure the safe and effective application of microneedles for drug delivery to the skin, the mechanical properties the microneedles and their ability to penetrate the skin are critical quality control parameters. While ex vivo and in vivo evaluations may be valuable to demonstrate actual skin penetration, they can be costly and difficult to accomplish consistently due to the inherent biological variability of the skin. On the other hand, in vitro approaches provide a facile means of characterising the intrinsic mechanical properties of the microneedles, independent of such biological variability. Thus, they can be used to predict and screen for the in vivo and ex vivo performance of new microneedle formulations. A variety of experimental configurations has been reported in the literature focusing on mechanical evaluations including compression tests and in vitro microneedle insertion studies using a non-biological skin simulant, Parafilm® M. However, there has been a paucity of data that address the comparability of the various experimental configurations. Here, we evaluated several methods for assessing the mechanical properties of microneedles in vitro, including their ability to insert into a non-biological skin simulant under a defined axial force, and share some insights into the experimental design and data interpretation.

Reverse engineering can assist in decoding the formula and manufacturing parameters employed in innovator formulations. Generic pharmaceutical industries use it to develop generic cheaper versions of innovator tablets. Herein, we report the systematic application of reverse engineering in determining the manufacturing process utilized by innovators to prepare tablet formulations. The outcome inferred that the critical information such as the granulation and solvent type in the innovator formulation could be identified by systematic analysis via scanning electron microscopy (SEM) images and sieve and texture analysis. Furthermore, critical investigation of the levels of fines generated during sieve analysis could reveal the tablet manufacturing process. It was observed that the maximum amount of fines was generated in the case of post-compression granules obtained by tablets prepared by direct compression. The hardness of granules is yet another major factor that could help to delineate the type of drying technique used in innovator manufacturing. Granules obtained from crushing a tablet prepared by wet granulation with tray drying were harder than those prepared by drying on a fluidized bed dryer (FBD). The outcome of this investigation may be helpful for formulation scientists working on the development of generic formulations.

The presence of the uppermost layer of the skin, referred to as the stratum corneum (SC), restricts the therapeutic efficacy of many drugs by acting as a barrier for drug molecules. Consequently, only a small number of molecules are likely to reach the intended target region. To overcome this impediment, transdermal drug delivery (TDD) that ablates the SC was developed, resulting in the formation of micropores that develop in a defined region of the skin's outer layer, which facilitates the delivery of extremely hydrophilic medications and macromolecules throughout the skin. The process of SC ablation involves the use of a range of physical techniques, which may be categorized as element-based heating, radiofrequency, laser, and suction ablation. Lately, there has been an increasing fascination with using physical ablative methods for skin treatment. Studies have shown that using ablative methods to improve drug delivery has many benefits, such as higher bioavailability, shorter treatment duration, and rapid recovery of the skin barrier. This review presents a comprehensive overview of the principles underlying a variety of methods for SC ablation, focusing on their potential for dramatically increasing skin absorption of drug molecules, delivering vaccines as a non-invasive alternative to injections, facilitating the delivery of macromolecules, and their application in drug delivery for chronic diseases like Alzheimer's disease or diabetes mellitus. In addition, we summarize some previous studies that compared the effectiveness of various SC ablation methods.

Presently, there are several challenges that need to be overcome in the development of treatments that can effectively inhibit tumor growth, prevent the spread of tumor metastases, and protect the host against recurrence. Accordingly, a powerful synergistic immunotherapy method was developed to achieve the treatment of cancer. Herein, we established an improvement in the nanoengineering of gold nanorod (GNR)-mediated photothermal therapy (PTT) with theranostic indocyanine green (ICG), which also produced heat for effective PTT under near-infrared (NIR) light. Furthermore, co-encapsulated resiquimod (R848) induced the activation of an immune response against the tumor. In addition, a nuclear-targeted transactivator of transcription (TAT) peptide conjugated with FA-functionalized GNRs was produced for intranuclear tumor-targeted in vivo photothermal therapeutic efficacy, inducing DAMPs for immunogenic cell death (ICD). Post-PTT release of R848-activated TLR7/8 is essential for the development of a potent antitumor immune response by increasing the number of T cells, which recognize and kill tumors. Thus, this integrated immunotherapy method can be utilized for both the diagnosis and treatment of tumor recurrence, providing novel opportunities for both basic and clinical research. Collectively, our findings suggest that nanotechnology may be a useful technique for improving the efficacy of vaccine-based cancer immunotherapy.

A mucus gel layer lines the luminal surface of tissues throughout the body to protect them from infectious agents and particulates. As a result, nanoparticle drug delivery systems delivered to these sites may become trapped in mucus and subsequently cleared before they can reach target cells. As such, optimizing the properties of nanoparticle delivery vehicles, such as their surface chemistry and size, is essential to improving their penetration through the mucus barrier. In previous work, we developed a mucin-based hydrogel that has viscoelastic properties like that of native mucus which can be further tailored to mimic specific mucosal tissues and disease states. Using this biomimetic hydrogel system, a 3D-printed array containing synthetic mucus barriers was created that is compatible with a 96-well plate enabling its use as a high-throughput screening platform for nanoparticle drug delivery applications. To validate this system, we evaluated several established design parameters to determine their impact on nanoparticle penetration through synthetic mucus barriers. Consistent with the literature, we found nanoparticles of smaller size and coated with a protective PEG layer more efficiently penetrated through synthetic mucus barriers. In addition, we evaluated a mucolytic (tris(2-carboxyethyl) phosphine, TCEP) for use as a permeation enhancer for mucosal drug delivery. In comparison to N-acetyl cysteine (NAC), we found TCEP significantly improved nanoparticle penetration through a disease-like synthetic mucus barrier. Overall, our results establish a new high-throughput screening approach using synthetic mucus barrier arrays to identify promising nanoparticle formulation strategies for drug delivery to mucosal tissues.

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Diclofenac (DF) is well established as a topical treatment option for conditions such as osteoarthritis. In investigating novel DF ion pairs for topical delivery, studies to determine the impact of various amino acids on the distribution of DF between octanol and aqueous environments were conducted. These studies identified the amino acid L-histidine hydrochloride monohydrate (LHSS) as an ion pair candidate for diclofenac sodium (DNa). Preliminary porcine skin permeation studies indicated that the addition of LHSS to DNa solutions increased the amount of DF that permeated through porcine skin. With increasing amounts of LHSS added, greater amounts of DF precipitated out of solution. In the present work, the solubility of DNa in various solvents was assessed, with the intention of identifying solvents in which DNa was most soluble. Binary systems comprising water and selected solvents were tested for both miscibility and the solubility of DNa and LHSS. The model system selected to evaluate novel ion pair formulations using porcine skin in vitro permeation studies under finite dose (10 μL) conditions comprised Transcutol® (TC) and water. The tested formulations contained DNa at concentrations of 5, 7.5 and 10 mg mL⁻¹. Higher LHSS concentrations were possible when the DNa concentrations were lower, and ranged from 10–25 mg mL⁻¹. However, increasing the DNa concentration to 10 mg mL⁻¹, without adding LHSS, resulted in a significant reduction in the amount of DF that partitioned and permeated, relative to formulations that contained either 5 mg mL⁻¹ DNa in combination with LHSS (at 12.5 or 25 mg mL⁻¹), or 7.5 mg mL⁻¹ DNa together with 12.5 mg mL⁻¹ LHSS. The current work confirms previous investigations, suggesting that the addition of LHSS to DNa in a formulation may increase the partition and permeation of DF.

We present an AmB-LIPOMER anchored with Acemannan (ACEM), a mannose ligand for active macrophage targeting, via mannose receptor mediated endocytosis (RME). The AmB-LIPOMER prepared by modified nanoprecipitation was anchored with ACEM by simple incubation. FITC was added to obtain fluorescent LIPOMERs. The LIPOMERs revealed a spherical morphology, an average size of 400–450 nm and a PDI < 0.3. Reduction in the zeta potential and FTIR confirmed ACEM anchoring. Flow cytometry demonstrated a >13-fold enhancement of the FITC-ACEM LIPOMER in vitro in RAW 264.7 macrophage cells, compared to the FITC-LIPOMER, ascribed to mannose receptor mediated endocytosis. This was confirmed by the decreased uptake of the FITC-ACEM LIPOMER in the mannose receptor blocking study. Nevertheless, we were surprised by an ∼2-fold decrease in the in vitro antileishmanial efficacy despite the augmented uptake of the ACEM LIPOMER. This poor efficacy was explained by the extensive localization of the FITC-ACEM LIPOMER in the lysosomal compartment, established by confocal microscopy, wherein AmB underwent rapid degradation. On the other hand phagocytic uptake and lipid mediated prolonged localization in the less harsh phagosome enabling lower degradation could have facilitated higher efficacy of the AmB-LIPOMER. The pharmacokinetic and biodistribution studies in rats revealed rapid and high reticuloendothelial system uptake. While the AmB-LIPOMER group exhibited no mortality, the mortality of 5 out of 6 animals in the AmB-ACEM LIPOMER group, within 15–30 minutes caused by lung necrosis was disturbing. While we propose an explanation for the toxicity, our study questions the rationale and safety of active targeting AmB using receptor mediated endocytosis.

Starch has emerged as a new attractive biopolymer for use in pharmaceutical applications, owing to its distinctive physical, chemical and functional properties. This biopolymer has several potential advantages: it is biocompatible, low cost, non-toxic and easily isolated from plant sources. In the pharmaceutical field, starch is used as a raw material for developing various drug delivery platforms. Generally, cassava starch (tapioca) is obtained from the swollen roots of the perennial shrub Manihot esculenta and it contains a low amount of amylose in contrast to other varieties of starches. Because of this reason, cassava starch exhibits various prime benefits, including a low gelatinization temperature, higher swelling power and a relatively high viscosity paste, making it a preferable excipient for pharmaceutical applications. However, cassava starches in their native form are not effective for many applications because of their inefficiency in handling various processing requirements like high temperature and diverse pH. Their applicability can be enhanced by starch modification. These functional starches have demonstrated outstanding prospects as primary excipients in many pharmaceutical formulations. In this article, we discuss the potential application of cassava starches in the pharmaceutical and biomedical fields, along with the toxicity assessment of modified cassava starches.