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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: closed (30 June 2023) | Viewed by 33797

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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 62223, Saudi Arabia
Interests: preformulation studies; cyclodextrins; solubility enhancement; modified release systems; niosomes; ocular delivery; irritation models
Special Issues, Collections and Topics in MDPI journals

Dr. Adel Al-Fatease

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Guest Editor

Pharmaceutics Department, College of Pharmacy, King Khalid University, Abha 62223, Saudi Arabia
Interests: drug delivery; cancer; pancreatic diseases; bioprinting; biosensor; nanotechnology
Special Issues, Collections and Topics in MDPI journals

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

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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.

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Keywords

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

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Editorial

Jump to: Research

3 pages, 174 KiB

Open AccessEditorial

Recent Advances in Long-Acting Drug Delivery and Formulations

by Adel Al Fatease and Hamdy Abdelkader

Pharmaceutics 2023, 15(11), 2519; https://doi.org/10.3390/pharmaceutics15112519 - 24 Oct 2023

Cited by 1 | Viewed by 1299

Abstract

Conventional immediate-release delivery systems are simple, industrially reproducible, acceptable, and easy-to-use by most patients [...] Full article

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

Research

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20 pages, 2936 KiB

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Hydroxypropyl Methylcellulose Bioadhesive Hydrogels for Topical Application and Sustained Drug Release: The Effect of Polyvinylpyrrolidone on the Physicomechanical Properties of Hydrogel

by Patrick Pan, Darren Svirskis, Geoffrey I. N. Waterhouse and Zimei Wu

Pharmaceutics 2023, 15(9), 2360; https://doi.org/10.3390/pharmaceutics15092360 - 21 Sep 2023

Cited by 8 | Viewed by 3760

Abstract

Hydrogels are homogeneous three-dimensional polymeric networks capable of holding large amounts of water and are widely used in topical formulations. Herein, the physicomechanical, rheological, bioadhesive, and drug-release properties of hydrogels containing hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP) were examined, and the intermolecular interactions between the polymers were explored. A three-level factorial design was used to form HPMC–PVP binary hydrogels. The physicomechanical properties of the binary hydrogels alongside the homopolymeric HPMC hydrogels were characterized using a texture analyzer. Rheological properties of the gels were studied using a cone and plate rheometer. The bioadhesiveness of selected binary hydrogels was tested on porcine skin. Hydrophilic benzophenone-4 was loaded into both homopolymeric and binary gels, and drug-release profiles were investigated over 24 h at 33 °C. Fourier transform infrared spectroscopy (FTIR) was used to understand the inter-molecular drug–gel interactions. Factorial design analysis supported the dominant role of the HPMC in determining the gel properties, rather than the PVP, with the effect of both polymer concentrations being non-linear. The addition of PVP to the HPMC gels improved adhesiveness without significantly affecting other properties such as hardness, shear-thinning feature, and viscosity, thereby improving bioadhesiveness for sustained skin retention without negatively impacting cosmetic acceptability or ease of use. The release of benzophenone-4 in the HPMC hydrogels followed zero-order kinetics, with benzophenone-4 release being significantly retarded by the presence of PVP, likely due to intermolecular interactions between the drug and the PVP polymer, as confirmed by the FTIR. The HPMC–PVP binary hydrogels demonstrate strong bioadhesiveness resulting from the addition of PVP with desirable shear-thinning properties that allow the formulation to have extended skin-retention times. The developed HPMC–PVP binary hydrogel is a promising sustained-release platform for topical drug delivery. Full article

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

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24 pages, 5002 KiB

Open AccessArticle

Salbutamol Attenuates Diabetic Skeletal Muscle Atrophy by Reducing Oxidative Stress, Myostatin/GDF-8, and Pro-Inflammatory Cytokines in Rats

by Anand Kumar, Priyanka Prajapati, Gurvinder Singh, Dinesh Kumar, Vikas Mishra, Seong-Cheol Kim, Chaitany Jayprakash Raorane, Vinit Raj and Sapana Kushwaha

Pharmaceutics 2023, 15(8), 2101; https://doi.org/10.3390/pharmaceutics15082101 - 8 Aug 2023

Cited by 2 | Viewed by 2639

Abstract

Type 2 diabetes is a metabolic disorder that leads to accelerated skeletal muscle atrophy. In this study, we aimed to evaluate the effect of salbutamol (SLB) on skeletal muscle atrophy in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats. Male Sprague Dawley rats were divided into four groups (n = 6): control, SLB, HFD/STZ, and HFD/STZ + SLB (6 mg/kg orally for four weeks). After the last dose of SLB, rats were assessed for muscle grip strength and muscle coordination (wire-hanging, rotarod, footprint, and actophotometer tests). Body composition was analyzed in live rats. After that, animals were sacrificed, and serum and gastrocnemius (GN) muscles were collected. Endpoints include myofibrillar protein content, muscle oxidative stress and antioxidants, serum pro-inflammatory cytokines (interleukin-1β, interleukin-2, and interleukin-6), serum muscle markers (myostatin, creatine kinase, and testosterone), histopathology, and muscle ¹H NMR metabolomics. Findings showed that SLB treatment significantly improved muscle strength and muscle coordination, as well as increased lean muscle mass in diabetic rats. Increased pro-inflammatory cytokines and muscle markers (myostatin, creatine kinase) indicate muscle deterioration in diabetic rats, while SLB intervention restored the same. Also, Feret’s diameter and cross-sectional area of GN muscle were increased by SLB treatment, indicating the amelioration in diabetic rat muscle. Results of muscle metabolomics exhibit that SLB treatment resulted in the restoration of perturbed metabolites, including histidine-to-tyrosine, phenylalanine-to-tyrosine, and glutamate-to-glutamine ratios and succinate, sarcosine, and 3-hydroxybutyrate (3HB) in diabetic rats. These metabolites showed a pertinent role in muscle inflammation and oxidative stress in diabetic rats. In conclusion, findings showed that salbutamol could be explored as an intervention in diabetic-associated skeletal muscle atrophy. Full article

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

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27 pages, 6287 KiB

Open AccessArticle

Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/β-Catenin/GSK-3β/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways

by Karema Abu-Elfotuh, Amina M. A. Tolba, Furqan H. Hussein, Ahmed M. E. Hamdan, Mohamed A. Rabeh, Saad A. Alshahri, Azza A. Ali, Sarah M. Mosaad, Nihal A. Mahmoud, Magdy Y. Elsaeed, Ranya M. Abdelglil, Rehab R. El-Awady, Eman Reda M. Galal, Mona M. Kamal, Ahmed M. M. Elsisi, Alshaymaa Darwish, Ayah M. H. Gowifel and Yasmen F. Mahran

Pharmaceutics 2023, 15(8), 2063; https://doi.org/10.3390/pharmaceutics15082063 - 31 Jul 2023

Cited by 7 | Viewed by 3202

Abstract

Alzheimer’s disease (AD) is a devastating illness with limited therapeutic interventions. The aim of this study is to investigate the pathophysiological mechanisms underlying AD and explore the potential neuroprotective effects of cocoa, either alone or in combination with other nutraceuticals, in an animal model of aluminum-induced AD. Rats were divided into nine groups: control, aluminum chloride (AlCl₃) alone, AlCl₃ with cocoa alone, AlCl₃ with vinpocetine (VIN), AlCl₃ with epigallocatechin-3-gallate (EGCG), AlCl₃ with coenzyme Q10 (CoQ10), AlCl₃ with wheatgrass (WG), AlCl₃ with vitamin (Vit) B complex, and AlCl₃ with a combination of Vit C, Vit E, and selenium (Se). The animals were treated for five weeks, and we assessed behavioral, histopathological, and biochemical changes, focusing on oxidative stress, inflammation, Wnt/GSK-3β/β-catenin signaling, ER stress, autophagy, and apoptosis. AlCl₃ administration induced oxidative stress, as evidenced by elevated levels of malondialdehyde (MDA) and downregulation of cellular antioxidants (Nrf2, HO-1, SOD, and TAC). AlCl3 also upregulated inflammatory biomarkers (TNF-α and IL-1β) and GSK-3β, leading to increased tau phosphorylation, decreased brain-derived neurotrophic factor (BDNF) expression, and downregulation of the Wnt/β-catenin pathway. Furthermore, AlCl₃ intensified C/EBP, p-PERK, GRP-78, and CHOP, indicating sustained ER stress, and decreased Beclin-1 and anti-apoptotic B-cell lymphoma 2 (Bcl-2) expressions. These alterations contributed to the observed behavioral and histological changes in the AlCl₃-induced AD model. Administration of cocoa, either alone or in combination with other nutraceuticals, particularly VIN or EGCG, demonstrated remarkable amelioration of all assessed parameters. The combination of cocoa with nutraceuticals attenuated the AD-mediated deterioration by modulating interrelated pathophysiological pathways, including inflammation, antioxidant responses, GSK-3β-Wnt/β-catenin signaling, ER stress, and apoptosis. These findings provide insights into the intricate pathogenesis of AD and highlight the neuroprotective effects of nutraceuticals through multiple signaling pathways. Full article

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

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22 pages, 4014 KiB

Open AccessArticle

Corneal Permeability and Uptake of Twenty-Five Drugs: Species Comparison and Quantitative Structure–Permeability Relationships

by Cleildo P. Santana, Brock A. Matter, Madhoosudan A. Patil, Armando Silva-Cunha and Uday B. Kompella

Pharmaceutics 2023, 15(6), 1646; https://doi.org/10.3390/pharmaceutics15061646 - 2 Jun 2023

Cited by 6 | Viewed by 2398

Abstract

The purpose of this study was to determine corneal permeability and uptake in rabbit, porcine, and bovine corneas for twenty-five drugs using an N-in-1 (cassette) approach and relate these parameters to drug physicochemical properties and tissue thickness through quantitative structure permeability relationships (QSPRs). A twenty-five-drug cassette containing β-blockers, NSAIDs, and corticosteroids in solution at a micro-dose was exposed to the epithelial side of rabbit, porcine, or bovine corneas mounted in a diffusion chamber, and the corneal drug permeability and tissue uptake were monitored using an LC-MS/MS method. Data obtained were used to construct and evaluate over 46,000 quantitative structure–permeability (QSPR) models using multiple linear regression, and the best-fit models were cross-validated by Y-randomization. Drug permeability was generally higher in rabbit cornea and comparable between bovine and porcine corneas. Permeability differences between species could be explained in part by differences in corneal thickness. Corneal uptake between species correlated with a slope close to 1, indicating generally similar drug uptake per unit weight of tissue. A high correlation was observed between bovine, porcine, and rabbit corneas for permeability and between bovine and porcine corneas for uptake (R² ≥ 0.94). MLR models indicated that drug characteristics such as lipophilicity (LogD), heteroatom ratio (HR), nitrogen ratio (NR), hydrogen bond acceptors (HBA), rotatable bonds (RB), index of refraction (IR), and tissue thickness (TT) are of great influence on drug permeability and uptake. When data for all species along with thickness as a parameter was used in MLR, the best fit equation for permeability was Log (% transport/cm²·s) = 0.441 LogD − 8.29 IR + 8.357 NR − 0.279 HBA − 3.833 TT + 10.432 (R² = 0.826), and the best-fit equation for uptake was Log (%/g) = 0.387 LogD + 4.442 HR + 0.105 RB − 0.303 HBA − 2.235 TT + 1.422 (R² = 0.750). Thus, it is feasible to explain corneal drug delivery in three species using a single equation. Full article

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

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23 pages, 2630 KiB

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

by Heba S. Abd-Ellah, Ramesh Mudududdla, Glen P. Carter and Jonathan B. Baell

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

Cited by 2 | Viewed by 1802

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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16 pages, 2439 KiB

Open AccessArticle

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

by Maria Abedin Zadeh, Raid G. Alany, Leila Satarian, Amin Shavandi, Mohamed Abdullah Almousa, Steve Brocchini and Mouhamad Khoder

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

Cited by 3 | Viewed by 2037

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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19 pages, 5431 KiB

Open AccessArticle

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

by Sravani Emani, Anil Vangala, Federico Buonocore, Niousha Yarandi and Gianpiero Calabrese

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

Cited by 10 | Viewed by 3245

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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15 pages, 4898 KiB

Open AccessArticle

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

by Heba A. Abou-Taleb, Mai E. Shoman, Tarek Saad Makram, Jelan A. Abdel-Aleem and Hamdy Abdelkader

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

Cited by 6 | Viewed by 3461

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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23 pages, 4399 KiB

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

by Saima Mahmood, Nauman Rahim Khan, Ghulam Razaque, Shefaat Ullah Shah, 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 12 | Viewed by 2782

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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12 pages, 1674 KiB

Open AccessArticle

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

by Yahia Alghazwani, Krishnaraju Venkatesan, Kousalya Prabahar, Mohamed El-Sherbiny, Nehal Elsherbiny and Mona Qushawy

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

Cited by 4 | Viewed by 2604

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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21 pages, 6638 KiB

Open AccessArticle

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

by Meghana Goravinahalli Shivananjegowda, Umme Hani, Riyaz Ali M. Osmani, Ali H. Alamri, Mohammed Ghazwani, Yahya Alhamhoom, Mohamed Rahamathulla, Sathishbabu Paranthaman, Devegowda Vishakante Gowda and Ayesha Siddiqua

Pharmaceutics 2023, 15(1), 221; https://doi.org/10.3390/pharmaceutics15010221 - 9 Jan 2023

Cited by 15 | Viewed by 2895

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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