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Special Issue "Recent Advances in Long-Acting Drug Delivery and Formulations"

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 30 June 2023 | Viewed by 6038

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Special Issue Editors

Dr. Hamdy Abdelkader

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Guest Editor

Pharmaceutics Department, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia
Interests: preformulation studies; cyclodextrins; solubility enhancement; modified release systems; niosomes; ocular delivery; irritation models

Dr. Adel Al-Fatease

E-Mail Website
Guest Editor

Pharmaceutics Department, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia
Interests: drug delivery; cancer; pancreatic diseases; bioprinting; biosensor; nanotechnology

Special Issue Information

Dear Colleagues,

Immediate-release delivery systems have been critiqued for not being able to consistently provide optimum therapy for chronic disease conditions, as well as for their potential to induce adverse effects. This is mainly due to the typical rapid, pulse-release and absorption patterns of their drug cargo, leading to rapidly fluctuating systemic drug concentration.

Long-acting drug delivery systems (LADDSs) encompass a range of formulations and technologies for precisely delivering drug molecules into target tissues either through the systemic circulation or via localized organs/tissues (e.g., skin, eye and specific lesions) for treating chronic diseases such as diabetes, cancer and brain disorders, as well as for treating age-related eye diseases. LADDSs have been shown to prolong drug release from several hours up to 3 years, depending on characteristics of the drug, disease and delivery system. LADDSs can offer potentially safer, more effective and patient-friendly treatment options compared to more invasive modes of drug administration such as repeated injections or minor surgical intervention. LADDSs include oral sustained release systems, injectable implants, in situ forming implants, inserts, wafers, transdermal patches, microspheres and nanoparticles.

Simple and scalable LADDS fabrication techniques such as the solvent casting method, other innovative delivery systems such as microneedle fabrication, and technologies such as electrospinning and 3D printing can yield personalized implantable devices.

The new knowledge obtained from novel research ideas and manuscripts will contribute to improving bioavailability, reducing unwanted side effects, achieving drug targeting or promoting better patient treatment adherence.

We would be much appreciative if you would consider being one of our authors contributing to this Special Issue. All types of submissions are welcome, including original research articles, and comprehensive reviews, etc.

Dr. Hamdy Abdelkader
Dr. Adel Al-Fatease
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

in situ forming implants
wafer
microneedle
3D printing
retinal diseases
cataract
glaucoma brain disorders
diabetes
cancer

Published Papers (7 papers)

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Research

Open AccessArticle

Novel Perspectives on the Design and Development of a Long-Acting Subcutaneous Raltegravir Injection for Treatment of HIV—In Vitro and In Vivo Evaluation

and

Pharmaceutics 2023, 15(5), 1530; https://doi.org/10.3390/pharmaceutics15051530 - 18 May 2023

Viewed by 359

Abstract

Antiretrovirals (ARVs) are a highly effective therapy for treatment and prevention of HIV infection, when administered as prescribed. However, adherence to lifelong ARV regimens poses a considerable challenge and places HIV patients at risk. Long-acting ARV injections may improve patient adherence as well as maintaining long-term continuous drug exposure, resulting in improved pharmacodynamics. In the present work, we explored the aminoalkoxycarbonyloxymethyl (amino-AOCOM) ether prodrug concept as a potential approach to long-acting ARV injections. As a proof of concept, we synthesised model compounds containing the 4-carboxy-2-methyl Tokyo Green (CTG) fluorophore and assessed their stability under pH and temperature conditions that mimic those found in the subcutaneous (SC) tissue. Among them, probe 21 displayed very slow fluorophore release under SC-like conditions (98% of the fluorophore released over 15 d). Compound 25, a prodrug of the ARV agent raltegravir (RAL), was subsequently prepared and evaluated using the same conditions. This compound showed an excellent in vitro release profile, with a half-life (t_½) of 19.3 d and 82% of RAL released over 45 d. In mice, 25 extended the half-life of unmodified RAL by 4.2-fold (t_½ = 3.18 h), providing initial proof of concept of the ability of amino-AOCOM prodrugs to extend drug lifetimes in vivo. Although this effect was not as pronounced as seen in vitro—presumably due to enzymatic degradation and rapid clearance of the prodrug in vivo—the present results nevertheless pave the way for development of more metabolically stable prodrugs, to facilitate long-acting delivery of ARVs. Full article

(This article belongs to the Special Issue Recent Advances in Long-Acting Drug Delivery and Formulations)

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Open AccessArticle

Maillard Reaction Crosslinked Alginate-Albumin Scaffolds for Enhanced Fenofibrate Delivery to the Retina: A Promising Strategy to Treat RPE-Related Dysfunction

Mohamed Abdullah Almousa

Steve Brocchini

and

Mouhamad Khoder

Pharmaceutics 2023, 15(5), 1330; https://doi.org/10.3390/pharmaceutics15051330 - 24 Apr 2023

Viewed by 556

Abstract

There are limited treatments currently available for retinal diseases such as age-related macular degeneration (AMD). Cell-based therapy holds great promise in treating these degenerative diseases. Three-dimensional (3D) polymeric scaffolds have gained attention for tissue restoration by mimicking the native extracellular matrix (ECM). The scaffolds can deliver therapeutic agents to the retina, potentially overcoming current treatment limitations and minimizing secondary complications. In the present study, 3D scaffolds made up of alginate and bovine serum albumin (BSA) containing fenofibrate (FNB) were prepared by freeze-drying technique. The incorporation of BSA enhanced the scaffold porosity due to its foamability, and the Maillard reaction increased crosslinking degree between ALG with BSA resulting in a robust scaffold with thicker pore walls with a compression modulus of 13.08 KPa suitable for retinal regeneration. Compared with ALG and ALG-BSA physical mixture scaffolds, ALG-BSA conjugated scaffolds had higher FNB loading capacity, slower release of FNB in the simulated vitreous humour and less swelling in water and buffers, and better cell viability and distribution when tested with ARPE-19 cells. These results suggest that ALG-BSA MR conjugate scaffolds may be a promising option for implantable scaffolds for drug delivery and retinal disease treatment. Full article

(This article belongs to the Special Issue Recent Advances in Long-Acting Drug Delivery and Formulations)

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Open AccessArticle

Chitosan Hydrogels Cross-Linked with Trimesic Acid for the Delivery of 5-Fluorouracil in Cancer Therapy

and

Pharmaceutics 2023, 15(4), 1084; https://doi.org/10.3390/pharmaceutics15041084 - 28 Mar 2023

Viewed by 615

Abstract

Chitosan exhibits unique properties making it a suitable material for drug delivery. Considering the rising popularity of hydrogels in this field, this work offers a comprehensive study of hydrogels constituted by chitosan and cross-linked with 1,3,5-benzene tricarboxylic acid (BTC; also known as trimesic acid). Hydrogels were prepared by cross-linking chitosan with BTC in different concentrations. The nature of the gels was studied through oscillatory amplitude strain and frequency sweep tests within the linear viscoelastic region (LVE) limit. The flow curves of the gels revealed shear thinning behavior. High G′ values imply strong cross-linking with improved stability. The rheological tests revealed that the strength of the hydrogel network increased with the cross-linking degree. Hardness, cohesiveness, adhesiveness, compressibility, and elasticity of the gels were determined using a texture analyzer. The scanning electron microscopy (SEM) data of the cross-linked hydrogels showed distinctive pores with a pore size increasing according to increasing concentrations (pore size range between 3–18 µm). Computational analysis was performed by docking simulations between chitosan and BTC. Drug release studies employing 5-fluorouracil (5-FU) yielded a more sustained release profile with 35 to 50% release among the formulations studied in a 3 h period. Overall, this work demonstrated that the presence of BTC as cross-linker leads to satisfactory mechanical properties of the chitosan hydrogel, suggesting potential applications in the sustained release of cancer therapeutics. Full article

(This article belongs to the Special Issue Recent Advances in Long-Acting Drug Delivery and Formulations)

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Open AccessArticle

Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen

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Pharmaceutics 2023, 15(2), 713; https://doi.org/10.3390/pharmaceutics15020713 - 20 Feb 2023

Viewed by 658

Abstract

Since its introduction to the market in the 1970s, ketoprofen has been widely used due to its high efficacy in moderate pain management. However, its poor solubility and ulcer side effects have diminished its popularity. This study prepared forms of ketoprofen modified with three basic excipients: tris, L-lysine, and L-arginine, and investigated their ability to improve water solubility and reduce ulcerogenic potential. The complexation/salt formation of ketoprofen and the basic excipients was prepared using physical mixing and coprecipitation methods. The prepared mixtures were studied for solubility, docking, dissolution, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), in vivo evaluation for efficacy (the writhing test), and safety (ulcerogenic liability). Phase solubility diagrams were constructed, and a linear solubility (AL type) curve was obtained with tris. Docking studies suggested a possible salt formation with L-arginine using Hirshfeld surface analysis. The order of enhancement of solubility and dissolution rates was as follows: L-arginine > L-lysine > tris. In vivo analgesic evaluation indicated a significant enhancement of the onset of action of analgesic activities for the three basic excipients. However, safety and gastric protection indicated that both ketoprofen arginine and ketoprofen lysine salts were more favorable than ketoprofen tris. Full article

(This article belongs to the Special Issue Recent Advances in Long-Acting Drug Delivery and Formulations)

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Open AccessArticle

Microwave-Treated Physically Cross-Linked Sodium Alginate and Sodium Carboxymethyl Cellulose Blend Polymer Film for Open Incision Wound Healing in Diabetic Animals—A Novel Perspective for Skin Tissue Regeneration Application

Memuna Ghafoor Shahid

Hassan A. Albarqi

Abdulsalam A. Alqahtani

Ali Alasiri

and

Hafiz Muhammad Basit

Pharmaceutics 2023, 15(2), 418; https://doi.org/10.3390/pharmaceutics15020418 - 27 Jan 2023

Cited by 2 | Viewed by 936

Abstract

This study aimed at developing the microwave-treated, physically cross-linked polymer blend film, optimizing the microwave treatment time, and testing for physicochemical attributes and wound healing potential in diabetic animals. Microwave-treated and untreated films were prepared by the solution casting method and characterized for various attributes required by a wound healing platform. The optimized formulation was tested for skin regeneration potential in the diabetes-induced open-incision animal model. The results indicated that the optimized polymer film formulation (MB-3) has significantly enhanced physicochemical properties such as high moisture adsorption (154.6 ± 4.23%), decreased the water vapor transmission rate (WVTR) value of (53.0 ± 2.8 g/m²/h) and water vapor permeability (WVP) value (1.74 ± 0.08 g mm/h/m²), delayed erosion (18.69 ± 4.74%), high water uptake, smooth and homogenous surface morphology, higher tensile strength (56.84 ± 1.19 MPa), and increased glass transition temperature and enthalpy (through polymer hydrophilic functional groups depicting efficient cross-linking). The in vivo data on day 16 of post-wounding indicated that the wound healing occurred faster with significantly increased percent re-epithelialization and enhanced collagen deposition with optimized MB-3 film application compared with the untreated group. The study concluded that the microwave-treated polymer blend films have sufficiently enhanced physical properties, making them an effective candidate for ameliorating the diabetic wound healing process and hastening skin tissue regeneration. Full article

(This article belongs to the Special Issue Recent Advances in Long-Acting Drug Delivery and Formulations)

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Open AccessArticle

The Combined Anti-Tumor Efficacy of Bioactive Hydroxyapatite Nanoparticles Loaded with Altretamine

Yahia Alghazwani

Krishnaraju Venkatesan

and

Pharmaceutics 2023, 15(1), 302; https://doi.org/10.3390/pharmaceutics15010302 - 16 Jan 2023

Cited by 1 | Viewed by 1058

Abstract

In the current study, the combined anti-tumor efficacy of bioactive hydroxyapatite nano- particles (HA-NPs) loaded with altretamine (ALT) was evaluated. The well-known fact that HA has great biological compatibility was confirmed through the findings of the hemolytic experiments and a maximum IC₅₀ value seen in the MTT testing. The preparation of HA-NPs was performed using the chemical precipitation process. An in vitro release investigation was conducted, and the results demonstrated the sustained drug release of the altretamine-loaded hydroxyapatite nanoparticles (ALT-HA-NPs). Studies using the JURKAT E6.1 cell lines MTT assay, and cell uptake, as well as in vivo pharmacokinetic tests using Wistar rats demonstrated that the ALT-HA-NPs were easily absorbed by the cells. A putative synergism between the action of the Ca²⁺ ions and the anticancer drug obtained from the carrier was indicated by the fact that the ALT-HA-NPs displayed cytotoxicity comparable to the free ALT at 1/10th of the ALT concentration. It has been suggested that a rise in intracellular Ca²⁺ ions causes cells to undergo apoptosis. Ehrlich’s ascites model in Balb/c mice showed comparable synergistic efficacy in a tumor regression trial. While the ALT-HA-NPs were able to shrink the tumor size by six times, the free ALT was only able to reduce the tumor volume by half. Full article

(This article belongs to the Special Issue Recent Advances in Long-Acting Drug Delivery and Formulations)

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Open AccessArticle

Development and Evaluation of Solid Lipid Nanoparticles for the Clearance of Aβ in Alzheimer’s Disease

Meghana Goravinahalli Shivananjegowda

Sathishbabu Paranthaman

Devegowda Vishakante Gowda

and

Ayesha Siddiqua

Pharmaceutics 2023, 15(1), 221; https://doi.org/10.3390/pharmaceutics15010221 - 09 Jan 2023

Cited by 2 | Viewed by 987

Abstract

Aggregation of Amyloid-β (Aβ) leads to the formation and deposition of neurofibrillary tangles and plaques which is the main pathological hallmark of Alzheimer’s disease (AD). The bioavailability of the drugs and their capability to cross the BBB plays a crucial role in the therapeutics of AD. The present study evaluates the Memantine Hydrochloride (MeHCl) and Tramiprosate (TMPS) loaded solid lipid nanoparticles (SLNs) for the clearance of Aβ on SHSY5Y cells in rat hippocampus. Molecular docking and in vitro Aβ fibrillation were used to ensure the binding of drugs to Aβ. The in vitro cell viability study showed that the M + T SLNs showed enhanced neuroprotection against SHSY5Y cells than the pure drugs (M + T PD) in presence of Aβ (80.35µM ± 0.455 µM) at a 3:1 molar ratio. The Box–Behnken Design (BBD) was employed to optimize the SLNs and the optimized M + T SLNs were further characterized by %drug entrapment efficiency (99.24 ± 3.24 of MeHCl and 89.99 ± 0.95 of TMPS), particle size (159.9 ± 0.569 nm), PDI (0.149 ± 0.08), Zeta potential (−6.4 ± 0.948 mV), Transmission Electron Microscopy (TEM), Atomic Force Microscopy (AFM) and in vitro drug release. The TEM & AFM analysis showed irregularly spherical morphology. In vitro release of SLNs was noted up to 48 h; whereas the pure drugs released completely within 3 hrs. M + T SLNs revealed an improved pharmacokinetic profile and a 4-fold increase in drug concentration in the brain when compared to the pure drug. Behavioral tests showed enhanced spatial memory and histological studies confirmed reduced Aβ plaques in rat hippocampus. Furthermore, the levels of Aβ decreased in AlCl₃-induced AD. Thus, all these noted results established that the M + T SLNs provide enhanced neuroprotective effects when compared to pure and individual drugs and can be a promising therapeutic strategy for the management of AD. Full article

(This article belongs to the Special Issue Recent Advances in Long-Acting Drug Delivery and Formulations)

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