Current drug delivery最新文献

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.

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.

Background: Wound healing is one of the major challenges in chronic diseases; the current treatment options are less effective with undesirable side effects and are expensive. Extensive research is carried out to develop cost-effective, natural, biodegradable wound dressings that can reduce oxidative stress and inflammation and prevent bacterial infections. Curcumin has a plethora of therapeutic applications; however, its low solubility limits its clinical use.

Objective: In this study, curcumin nanoparticles (Cur NP) and curcumin-chitosan nanoparticles (CCNP) were incorporated into the chitosan collagen vanillin scaffold, characterized, and investigated their potential wound healing properties.

Methods: The nano-scaffolds were prepared by freeze-drying method and were characterized using Fourier transform infrared spectroscopy, X-ray diffraction, nanoparticle tracking analysis, and scanning electron microscopy. The drug release, antioxidant, antibacterial, and wound healing properties were assessed by in vitro assays.

Results: Cur nano-scaffolds showed particle sizes of 195.9 nm and 110.6 nm for Cur NP+VC and CCNP+VC, respectively. The curcumin encapsulated in the Cur NP+VC and CC+VC nano-scaffolds showed a release profile of > 60% and an improved antioxidant activity of greater than 80%. The nanoscaffolds were antagonistic against Escherichia coli and Staphylococcus aureus and enhanced wound healing capacity of 85.62 % and 77.05% in the murine cell line.

Conclusion: The curcumin nano-scaffold is a biodegradable and effective drug delivery system for topical use that can act as an antioxidant, facilitate wound healing, as well as prevent bacterial infections.

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.

Background: Coenzyme Q10 (Q10) is a powerful lipophilic antioxidant with poor solubility in aqueous media. Curcumin (Cur) is a natural polyphenolic phytochemical molecule with poor aqueous solubility. The liposome is an improved administration of drugs because it is biocompatible and permeable for nutraceutical delivery. Chitosan, a hydrophilic polymer, is often used as a polymer coating for its good biocompatible and biodegradable properties, and its relatively low toxicity level.

Methods: Q10 and Cur co-loaded liposomes coated with chitosan (Q10-Cur-Lip-Chi) were constructed. The co-encapsulation of Q10 and Cur in liposomes coated with chitosan was verified by TEM, DLS, DSC, FT-IR, and XRPD. The release profile and antioxidant activity of Q10-Cur-Lip-Chi were accessed.

Results: The particle size of Q10-Cur-Lip-Chi was about 1440 nm with narrow particle distribution. A satisfactory encapsulation efficiency (EE) of Q10 was about 98%, and 25% for that of Cur. Q10-Cur- Lip-Chi showed higher solubility and better pH resistance with 98.5% of Q10 and Cur retention at pH 7.0 - 9.0. Q10-Cur-Lip also showed great salt stability with a vesicle size change of less than 5%. PSof Q10-Cur-Lip-Chi changed less than 10% at 4°C of storage. Q10-Cur-Lip-Chi also exhibited a good controlled release profile with its accumulative release of less than 34% for Q10 and 30% for curcumin after 24 h. The Q10-Cur-Lip-Chi performed a synergistic effect on antioxidant activity reaching 41.86±1.84%, which was 5.9 times higher than that of Q10, 2.5 times higher than that of Cur, and 1.7 times higher than that of the mixture.

Conclusion: The co-encapsulation Q10-Cur-Lip-Chi improves the solubility and stability of Q10 and Cur for good release performance and antioxidative activity.

Retinoids represent a class of chemical compounds derived from or structurally and functionally related to vitamin A. Retinoids play crucial roles in regulating a range of crucial biological processes spanning embryonic development to adult life. These include regulation of cell proliferation, differentiation, and cell death. Due to their promising characteristics, retinoids emerged as potent anti-cancer agents, and their effects were validated in vitro and in vivo preclinical models of several solid and hematological malignancies. However, their clinical translation remained limited due to poor water solubility, photosensitivity, short half-life, and toxicity. The development of retinoid delivery formulations was extensively studied to overcome these limitations. This review will summarize some preclinical and commercial synthetic retinoids in cancer and discuss their different delivery systems.

Background: Diacerein, an osteoarthiritis drug, experiences slow topical permeation due to limited solubility. Additionally, it shows a laxative effect due to acid/base hydrolysis of the drug in the colon.

Objective: Diacerein solubility was improved to increase percutaneous drug delivery.

Methods: To improve saturation solubility of the drug, Diacerein was pre-treated with Polysorbate 80 aqueous solution (1% v/v) to obtain lyophilized powder after wet milling or formulated as solid dispersion using PEG 4000 by fusion method. The lyophilized Diacerein in hydroxypropyl methylcellulose (HPMC 8% w/w) and polyvinyl pyrrolidone (PVP 30% w/w) matrix, with PEG 400 as co-solvent, provided an optimized array. The solid dispersion was loaded in the CMC based gel for subsequent administration on dissolving microneedle-treated skin.

Results: The addition of PEG 400 increased Diacerein loading in microneedles to 390.35±4.28 μg per array. The lyophilized drug displayed amorphous characteristics in the dissolving microneedles as per XRD analysis. SEM photographs showed uniformity in the surface topology of microneedles. The needles showed rapid polymer dissolution within 5 minutes, whereas methylene-blue distribution confirmed the formation of microcavities in excised rat skin. The drug-loaded arrays showed better permeation (74.39%) and skin deposition (15.75%) after 24 hours, however, ⁓12% of Diacerein remained in the baseplate. This led to the tailoring of CMC-based gel (3% w/v) containing 0.4% solid dispersion of Diacerein. When compared to untreated skin, the gel improved permeation rate by 2.43 folds through aqueous microchannels generated by dissolving microneedle pre-treatment and allowed 98% drug permeation. The quasi-Fickian diffusion mechanism was found to drive ex vivo release kinetics, with a shorter lag time (0.88 h) and higher flux (26.65 μg/sq.cm.h). Microneedle-assisted Diacerein gel showed a positive anti-inflammatory effect in the paw edema model and reduced diarrheal episodes in comparison to the marketed oral formulation. The gel showed desired characteristics at 5°C±2°C when tested under accelerated stability conditions.

Conclusion: The present study reports for the first time the verification of efficacy and safety to advocate the suitability of Diacerein for percutaneous delivery through dissolving microneedle-treated skin.

Background: Cancer, an uncontrolled multistage disease causing swift division of cells, is a leading disease with the highest mortality rate. Cellular heterogeneity, evading growth suppressors, resisting cell death, and replicative immortality drive the tumor progression by resisting the therapeutic action of existing anticancer drugs through a series of intrinsic and extrinsic cellular interactions. The innate cellular mechanisms also regulate the replication process as a fence against proliferative signaling, enabling replicative immortality through telomere dysfunction.

Area covered: The conventional genotoxic drugs have several off-target and collateral side effects associated with them. Thus, the need for the therapies targeting cyclin-dependent kinases or P13K signaling pathway to expose cancer cells to immune destruction, deactivation of invasion and metastasis, and maintaining cellular energetics is imperative. Compounds with anticancer attributes isolated from plants and rich in alkaloids, terpenes, and polyphenols have proven to be less toxic and highly targetspecific, making them biologically significant. This has opened a gateway for the exploration of more novel plant molecules by signifying their role as anticancer agents in synergy and alone, making them more effective than the existing cytotoxic regimens.

Expert opinion: In this context, the current review presented recent data on cancer cases around the globe, along with discussing the fundamentals of proliferative signaling and replicative immortality of cancer cells. Recent findings were also highlighted, including antiproliferative and antireplicative action of plant-derived compounds, besides explaining the need for improving drug delivery systems.

Amorphous solid dispersion (ASD) is a popular concept for improving the dissolution and oral bioavailability of poorly water-soluble drugs. ASD faces two primary challenges of low drug loading and recrystallization upon storage. Several polymeric carriers are used to fabricate a stable ASD formulation with a high drug load. The role of silica in this context has been proven significant. Different types of silica, porous and nonporous, have been used to develop ASD. Amorphous drugs get entrapped into silica pores or adsorbed on their surface. Due to high porosity and wide surface area, silica provides better drug dissolution and high drug loading. Recrystallization of amorphous drugs is inhibited by limited molecular ability inside the delicate pores due to hydrogen bonding with the surface silanol groups. A handful of researches have been published on silica-based ASD, where versatile types of silica have been used. However, the effect of different kinds of silica on product stability and drug loading has been rarely addressed. The present study analyzes multiple porous and nonporous silica types and their distinct role in developing a stable ASD. Emphasis has been given to various types of silica which are commonly used in the pharmaceutical industry.

Nanosponges are colloidal and crosslinked nanocarriers consisting of a solid mesh-like network with nanocavities to encompass various types of substances like antineoplastic, proteins, peptides, volatile oil, DNA and then incorporated into topical medications that are mainly formulated such as gels, creams, lotions, ointments, liquid and powders etc. for topical drug delivery system. In the polymeric construction of nanosponges, the release of enthalpy-rich water molecules accounts for high complexation efficiency for different molecular substances. The benefits of nanosponges involve the extended and controlled release of encapsulated particles with excellent competence and great stability. Nanosponges assume a significant part in new varieties of medicaments, beautifiers, farming, horticulture, high atomic weight containing proteins, innovative fire retardants, gas transporters, and water filters. Nanosponges are a novel technology that offers controlled and targeted drug delivery by various routes like oral, parenteral, and topical routes. Nanosponges are an effective transporter for biologically active ingredients; therefore, it is broadly employed in anti-cancer, antiviral, antiplatelet, and antilipidemic therapy. This review article gives attention to the general introduction, merits and demerits, classification, characteristic features, procedures for developing nanosponges, and numerous factors which affect nanosponge formulation, evaluation parameters, and applications in the medicinal industry.