Displaying publications 21 - 38 of 38 in total

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  1. Zainal-Abidin MH, Hayyan M, Ngoh GC, Wong WF, Looi CY
    J Control Release, 2019 12 28;316:168-195.
    PMID: 31669211 DOI: 10.1016/j.jconrel.2019.09.019
    The applications of eutectic systems, including deep eutectic solvents (DESs), in diverse sectors have drawn significant interest from researchers, academicians, engineers, medical scientists, and pharmacists. Eutecticity increases drug dissolution, improves drug penetration, and acts as a synthesis route for drug carriers. To date, DESs have been extensively explored as potential drug delivery systems on account of their unique properties such as tunability and chemical and thermal stability. This review discusses two major topics: first, the application of eutectic mixtures (before and after the introduction of DES) in the field of drug delivery systems, and second, the most promising examples of DES pharmaceutical activity. It also considers future prospects in the medical and biotechnological fields. In addition to the application of DESs in drug delivery systems, they show greatly promising pharmaceutical activities, including anti-fungal, anti-bacterial, anti-viral, and anti-cancer activities. Eutecticity is a valid strategy for overcoming many obstacles inherently associated with either introducing new drugs or enhancing drug delivery systems.
  2. Ichimizu S, Watanabe H, Maeda H, Hamasaki K, Ikegami K, Chuang VTG, et al.
    J Control Release, 2019 06 28;304:156-163.
    PMID: 31082432 DOI: 10.1016/j.jconrel.2019.05.015
    We recently developed a cell-penetrating drug carrier composed of albumin (HSA) combined with palmitoyl-cyclic-(D-Arg)12. While it is possible that the palmitoyl-cyclic-(D-Arg)12/HSA enters the cell mainly via macropinocytosis, the mechanism responsible for the induction of macropinocytosis and endosomal escape remain unknown. We report herein that palmitoyl-cyclic-(D-Arg)12/HSA might interact with heparan sulfate proteoglycan and the chemokine receptor CXCR4 followed by multiple activations of the PKC/PI3K/JNK/mTOR signaling pathways to induce macropinocytosis. This result was further confirmed by a co-treatment with 70 kDa dextran, a macropinocytosis marker. Using liposomes that mimic endosomes, the leakage of 5,6-carboxyfluorescein from liposome was observed in the presence of palmitoyl-cyclic-(D-Arg)12/HSA only in the case of the anionic late endosome-like liposomes but not the neutral early endosome-like liposomes. Heparin largely inhibited this leakage, suggesting the importance of electrostatic interactions between palmitoyl-cyclic-(D-Arg)12/HSA and the late-endosomal membrane. Immunofluorescence staining and Western blotting data indicated that the intact HSA could be transferred from endosomes to the cytosol. These collective data suggest that the palmitoyl-cyclic-(D-Arg)12/HSA is internalized via macropinocytosis and intact HSA is released from the late endosomes to the cytoplasm before the endosomes fuse with lysosomes. Palmitoyl-cyclic-(D-Arg)12/HSA not only functions as an intracellular drug delivery carrier but also as an inducer of macropinocytosis.
  3. Zaman R, Islam RA, Ibnat N, Othman I, Zaini A, Lee CY, et al.
    J Control Release, 2019 05 10;301:176-189.
    PMID: 30849445 DOI: 10.1016/j.jconrel.2019.02.016
    Macromolecular protein and peptide therapeutics have been proven to be effective in treating critical human diseases precisely. Thanks to biotechnological advancement, a huge number of proteins and peptide therapeutics were made their way to pharmaceutical market in past few decades. However, one of the biggest challenges to be addressed for protein therapeutics during clinical application is their fast degradation in serum and quick elimination owing to enzymatic degradation, renal clearance, liver metabolism and immunogenicity, attributing to the short half-lives. Size and hydrophobicity of protein molecules make them prone to kidney filtration and liver metabolism. On the other hand, proteasomes responsible for protein destruction possess the capability of specifically recognizing almost all kinds of foreign proteins while avoiding any unwanted destruction of cellular components. At present almost all protein-based drug formulations available in market are administered intravenously (IV) or subcutaneously (SC) with high dosing at frequent interval, eventually creating dose-fluctuation-related complications and reducing patient compliance vastly. Therefore, artificially increasing the therapeutic half-life of a protein by attaching to it a molecule that increases the overall size (eg, PEG) or helps with receptor mediated recycling (eg, albumin), or manipulating amino acid chain in a way that makes it more prone towards aggregate formation, are some of the revolutionary approaches to avoid the fast degradation in vivo. Half-life extension technologies that are capable of dramatically enhancing half-lives of proteins in circulation (2-100 folds) and thus improving their overall pharmacokinetic (PK) parameters have been successfully applied on a wide range of protein therapeutics from hormones and enzymes, growth factor, clotting factor to interferon. The focus of the review is to assess the technological advancements made so far in enhancing circulatory half-lives and improving therapeutic potency of proteins.
  4. Thevendran R, Sarah S, Tang TH, Citartan M
    J Control Release, 2020 07 10;323:530-548.
    PMID: 32380206 DOI: 10.1016/j.jconrel.2020.04.051
    Aptamers are a class of folded nucleic acid strands capable of binding to different target molecules with high affinity and selectivity. Over the years, they have gained a substantial amount of interest as promising molecular tools for numerous medical applications, particularly in targeted therapeutics. However, only the different treatment approaches and current developments of aptamer-drug therapies have been discussed so far, ignoring the crucial technical and functional aspects of constructing a therapeutically effective aptamer-driven drug delivery system that translates to improved in-vivo performance. Hence, this paper provides a comprehensive review of the strategies used to improve the therapeutic performance of aptamer-guided delivery systems. We focus on the different functional features such as drug deployment, payload capacity, in-vivo stability and targeting efficiency to further our knowledge in enhancing the cell-specific delivery of aptamer-drug conjugates. Each reported strategy is critically discussed to emphasize both the benefits provided in comparison with other similar techniques and to outline their potential drawbacks with respect to the molecular properties of the aptamers, the drug and the system to be designed. The molecular architecture and design considerations for an efficient aptamer-based delivery system are also briefly elaborated.
  5. Low LE, Wu J, Lee J, Tey BT, Goh BH, Gao J, et al.
    J Control Release, 2020 Aug 10;324:69-103.
    PMID: 32423874 DOI: 10.1016/j.jconrel.2020.05.014
    The recent designs of dynamic nanoassemblies exploiting the tumor-targeting properties have received increasing attention for tumor imaging and therapy due to their tumor-specific delivery and enhanced antitumor efficacy. However, these designs are mainly focused on the macroscopic tumor therapeutic effect, while the nano-bio interactions in the tumor microenvironment (TME) remain poorly understood. This review aims to provide an overview of the development of tumor-responsive nanoassemblies towards the imaging, therapy and TME modulation in the tumor site. The tumor biology leading to TME formation and the potential TME properties for the practicable design of tumor-targeting nanoassemblies has been outlined. Furthermore, the various approaches for TME modification and the realization via dynamic nanoassemblies for enhanced tumor therapy were reviewed. Lastly, the prospects of these methods were briefly discussed. These strategies may inspire the development of new combinational cancer therapeutics.
  6. Mehta M, Paudel KR, Shukla SD, Allam VSRR, Kannaujiya VK, Panth N, et al.
    J Control Release, 2021 09 10;337:629-644.
    PMID: 34375688 DOI: 10.1016/j.jconrel.2021.08.010
    Nuclear factor κB (NFκB) is a unique protein complex that plays a major role in lung inflammation and respiratory dysfunction. The NFκB signaling pathway, therefore becomes an avenue for the development of potential pharmacological interventions, especially in situations where chronic inflammation is often constitutively active and plays a key role in the pathogenesis and progression of the disease. NFκB decoy oligodeoxynucleotides (ODNs) are double-stranded and carry NFκB binding sequences. They prevent the formation of NFκB-mediated inflammatory cytokines and thus have been employed in the treatment of a variety of chronic inflammatory diseases. However, the systemic administration of naked decoy ODNs restricts their therapeutic effectiveness because of their poor pharmacokinetic profile, instability, degradation by cellular enzymes and their low cellular uptake. Both structural modification and nanotechnology have shown promising results in enhancing the pharmacokinetic profiles of potent therapeutic substances and have also shown great potential in the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. In this review, we examine the contribution of NFκB activation in respiratory diseases and recent advancements in the therapeutic use of decoy ODNs. In addition, we also highlight the limitations and challenges in use of decoy ODNs as therapeutic molecules, cellular uptake of decoy ODNs, and the current need for novel delivery systems to provide efficient delivery of decoy ODNs. Furthermore, this review provides a common platform for discussion on the existence of decoy ODNs, as well as outlining perspectives on the latest generation of delivery systems that encapsulate decoy ODNs and target NFκB in respiratory diseases.
  7. Vejan P, Khadiran T, Abdullah R, Ahmad N
    J Control Release, 2021 Nov 10;339:321-334.
    PMID: 34626724 DOI: 10.1016/j.jconrel.2021.10.003
    Controlled release fertilizer (CRF) plays a crucial yet necessary part in the sustainable agriculture industry. An alarming rise in call for crop production directly influences the increasing need for synthetically derived fertilizers and pesticides production. The application of CRF has been a gamechanger as an environmentally sustainable pathway to increase crop yields by paving desired phase of plant growth via a direct or indirect mechanism. The mechanism of CRF does not only decreases nutrient dissipation due to volatilization and leaching, but also provides a precisely appropriate nutrient release design that is suitable in the physiological and biochemical aspect of the plant growth. However, CRF is not deployed on larger scale of commercial agriculture practices due to being expensive, has relatively low efficiency in releasing nutrients and its coatings are largely composed of petroleum-based synthetic polymers. Alternatively, there are many polymers derived from renewable and biodegradable sources that can be used as coating material for CRF in the form of bio-nanocomposites. Having said that, there is an apparent gap between the mechanism of the CRFs for promoting plant growth and the prominent role of the nanocomposites especially bio-nanocomposites as coating material for CRF synthesis, thus the importance of nanotechnology application in enhancing the effectiveness of CRF. Therefore, this review attempts to bridge the stated gap and summarizes the comprehensive developments, application mechanisms and future potential of CRF as a fertilizer for crop sustainability.
  8. Bhattacharjee G, Gohil N, Khambhati K, Mani I, Maurya R, Karapurkar JK, et al.
    J Control Release, 2022 Feb 08.
    PMID: 35149141 DOI: 10.1016/j.jconrel.2022.02.005
    A single gene mutation can cause a number of human diseases that affect quality of life. Until the development of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein (Cas) systems, it was challenging to correct a gene mutation to avoid disease by reverting phenotypes. The advent of CRISPR technology has changed the field of gene editing, given its simplicity and intrinsic programmability, surpassing the limitations of both zinc-finger nuclease and transcription activator-like effector nuclease and becoming the method of choice for therapeutic gene editing by overcoming the bottlenecks of conventional gene-editing techniques. Currently, there is no commercially available medicinal cure to correct a gene mutation that corrects and reverses the abnormality of a gene's function. Devising reprogramming strategies for faithful recapitulation of normal phenotypes is a crucial aspect for directing the reprogrammed cells toward clinical trials. The CRISPR-Cas9 system has been promising as a tool for correcting gene mutations in maladies including blood disorders and muscular degeneration as well as neurological, cardiovascular, renal, genetic, stem cell, and optical diseases. In this review, we highlight recent developments and utilization of the CRISPR-Cas9 system in correcting or generating gene mutations to create model organisms to develop deeper insights into diseases, rescue normal gene functionality, and curb the progression of a disease.
  9. Geo HN, Murugan DD, Chik Z, Norazit A, Foo YY, Leo BF, et al.
    J Control Release, 2022 Jan 24;343:237-254.
    PMID: 35085695 DOI: 10.1016/j.jconrel.2022.01.033
    Acute kidney injury (AKI) causes considerable morbidity and mortality, particularly in the case of post-cardiac infarction or kidney transplantation; however, the site-specific accumulation of small molecule reno-protective agents for AKI has often proved ineffective due to dynamic fluid and solute excretion and non-selectivity, which impedes therapeutic efficacy. This article reviews the current status and future trajectories of renal nanomedicine research for AKI management from pharmacological and clinical perspectives, with a particular focus on appraising nanosized drug carrier (NDC) use for the delivery of reno-protective agents of different pharmacological classes and the effectiveness of NDCs in improving renal tissue targeting selectivity and efficacy of said agents. This review reveals the critical shift in the role of the small molecule reno-protective agents in AKI pharmacotherapy - from prophylaxis to treatment - when using NDCs for delivery to the kidney. We also highlight the need to identify the accumulation sites of NDCs carrying reno-protective agents in renal tissues during in vivo assessments and detail the less-explored pharmacological classes of reno-protective agents whose efficacies may be improved via NDC-based delivery. We conclude the paper by outlining the challenges and future perspectives of NDC-based reno-protective agent delivery for better clinical management of AKI.
  10. Ashrafizadeh M, Delfi M, Zarrabi A, Bigham A, Sharifi E, Rabiee N, et al.
    J Control Release, 2022 Nov;351:50-80.
    PMID: 35934254 DOI: 10.1016/j.jconrel.2022.08.001
    The site-specific delivery of antitumor agents is of importance for providing effective cancer suppression. Poor bioavailability of anticancer compounds and the presence of biological barriers prevent their accumulation in tumor sites. These obstacles can be overcome using liposomal nanostructures. The challenges in cancer chemotherapy and stimuli-responsive nanocarriers are first described in the current review. Then, stimuli-responsive liposomes including pH-, redox-, enzyme-, light-, thermo- and magneto-sensitive nanoparticles are discussed and their potential for delivery of anticancer drugs is emphasized. The pH- or redox-sensitive liposomes are based on internal stimulus and release drug in response to a mildly acidic pH and GSH, respectively. The pH-sensitive liposomes can mediate endosomal escape via proton sponge. The multifunctional liposomes responsive to both redox and pH have more capacity in drug release at tumor site compared to pH- or redox-sensitive alone. The magnetic field and NIR irradiation can be exploited for external stimulation of liposomes. The light-responsive liposomes release drugs when they are exposed to irradiation; thermosensitive-liposomes release drugs at a temperature of >40 °C when there is hyperthermia; magneto-responsive liposomes release drugs in presence of magnetic field. These smart nanoliposomes also mediate co-delivery of drugs and genes in synergistic cancer therapy. Due to lack of long-term toxicity of liposomes, they can be utilized in near future for treatment of cancer patients.
  11. Zaman R, Islam RA, Chowdhury EH
    J Control Release, 2022 11;351:779-804.
    PMID: 36202153 DOI: 10.1016/j.jconrel.2022.09.066
    The established cancer treatment strategy in clinical setting is based on chemo and radiation therapy, having limitations due to severe side-effects and drug-resistance. Small molecule chemo-drugs target any fast-dividing cells irrespective of healthy or defective origin. As a result, a substantial amount of healthy tissue is also destroyed. Moreover, failure to recognize the heterogeneity of tumour tissue results in drug-resistance over the course of time. On the other hand, peptides and proteins actively target somatic changes that are signature to any specific tumour tissue. Development and metastasis of cancer cells require unique disruption/alteration of protein activity. Identification of those wild and cancerous genotypes and phenotypes is the key to establishing easy 'targets' for protein based targeted therapeutics. The approach is cytostatic and tissue specific, which reduces drug toxicity. Biopharmaceutical products based on proteins and peptides are slowly re-directing oncology from cytotoxic small molecular treatment approach to target oriented cytostatic strategy. This review focuses on current and upcoming peptide and protein-based precision therapeutics. At the same time, the study also shades light on the technological advancement in the field of protein and peptide-based therapeutics.
  12. Saadi S, Saari N, Abdulkarim MS, Ghazali HM, Anwar F
    J Control Release, 2018 03 28;274:93-101.
    PMID: 29031897 DOI: 10.1016/j.jconrel.2017.10.011
    Cell impurities are an emerging nucleating molecular barriers having the capability in disordering the metabolic chain reactions of proteolysis, glycolysis and lipolysis. Their massive effects induced by copolymer crystal growth in compaction with metal and mineral transients are extended as well as in damaging DNA and mRNA structure motif and other molecular assembly e.g. histones structure unites. Their polycrystalline packing modes, polydispersity and their tendency to surface and interface adhesion prompted us in structuring scaffold biomaterials enriched with biopeptides, layered by phospho-glycerides ester-forms. The interface tension of the formed map is flexible and dependent to the surface exposure and its collapse modes to the surrounding molecular ligands. Thus, the attempts in increasing surface exposure e.g. the viscoelastic of structured lipopeptides and types of formed network structures interplays an extra- conjugating biomolecules having a least cytotoxicity effects to cells constituents. Disulfides molecules are selected to be the key regulatory element in rejoining both lipidic and proteic moieties by disordering atoms status via chemical ionization using organic catalyst. The insertion of methionine based peptidic chain at the lateral surfaces of scaffold biomaterials enhances the electron-meta-static motions by raising a molecular disordering status at distinct regions of the map e.g. epimerization into a nonpolar side that helps the chemical conjunction of disulfide groups with the esterified phosphoglycerides mono-layers. These effects in turn are accomplished by the formation of meso-sphere nonpolar- vesicles. The oxidation of disulfide group would alter the ordering of initial molecules by raising a newly molecular disorders to the map with high polarity to surface regions. In the same time indicates a continuation in the crystallization growth factor via a low chemical lesions between the impurities and a supersaturation in the intra-atomic distances with maximum cross linking to the deformed ligand with scaffold biomaterials.
  13. Ghanghoria R, Kesharwani P, Tekade RK, Jain NK
    J Control Release, 2018 01 10;269:277-301.
    PMID: 27840168 DOI: 10.1016/j.jconrel.2016.11.002
    Cancer is a prime healthcare problem that is significantly responsible for universal mortality. Despite distinguished advancements in medical field, chemotherapy is still the mainstay for the treatment of cancers. During chemotherapy, approximately 90% of the administered dose goes to normal tissues, with mere 2-5% precisely reaching the cancerous tissues. Subsequently, the resultant side effects and associated complications lead to dose reduction or even discontinuance of the therapy. Tumor directed therapy therefore, represents a fascinating approach to augment the therapeutic potential of anticancer bioactives as well as overcomes its side effects. The selective overexpression of LHRH receptors on human tumors compared to normal tissues makes them a suitable marker for diagnostics, molecular probes and targeted therapeutics. These understanding enabled the rational to conjugate LHRH with various cytotoxic drugs (doxorubicin, DOX; camptothecin etc.), cytotoxic genes [small interfering RNA (siRNA), micro RNA (miRNA)], as well as therapeutic nanocarriers (nanoparticles, liposomes or dendrimers) to facilitate their tumor specific delivery. LHRH conjugation enhances their delivery via LHRH receptor mediated endocytosis. Numerous cytotoxic analogs of LHRH were developed over the past two decades to target various types of cancers. The potency of LHRH compound were reported to be as high as 5,00-10,00 folds compared to parent molecules. The objective of this review article is to discuss reports on various LHRH analogs with special emphasis on their prospective application in the medical field. The article also focuses on the attributes that must be taken into account while designing a LHRH therapeutics with special account to the biochemistry and applications of these conjugates. The record on various cytotoxic analogs of LHRH are also discussed. It is anticipated that the knowledge of therapeutic and toxicological aspects of LHRH compounds will facilitate the development of a more systematic approach to the targeted delivery of cytotoxic agents using peptides.
  14. Irfan SA, Razali R, KuShaari K, Mansor N, Azeem B, Ford Versypt AN
    J Control Release, 2018 02 10;271:45-54.
    PMID: 29274697 DOI: 10.1016/j.jconrel.2017.12.017
    Nutrients released into soils from uncoated fertilizer granules are lost continuously due to volatilization, leaching, denitrification, and surface run-off. These issues have caused economic loss due to low nutrient absorption efficiency and environmental pollution due to hazardous emissions and water eutrophication. Controlled-release fertilizers (CRFs) can change the release kinetics of the fertilizer nutrients through an abatement strategy to offset these issues by providing the fertilizer content in synchrony with the metabolic needs of the plants. Parametric analysis of release characteristics of CRFs is of paramount importance for the design and development of new CRFs. However, the experimental approaches are not only time consuming, but they are also cumbersome and expensive. Scientists have introduced mathematical modeling techniques to predict the release of nutrients from the CRFs to elucidate fundamental understanding of the dynamics of the release processes and to design new CRFs in a shorter time and with relatively lower cost. This paper reviews and critically analyzes the latest developments in the mathematical modeling and simulation techniques that have been reported for the characteristics and mechanisms of nutrient release from CRFs. The scope of this review includes the modeling and simulations techniques used for coated, controlled-release fertilizers.
  15. Wen MM, El-Salamouni NS, El-Refaie WM, Hazzah HA, Ali MM, Tosi G, et al.
    J Control Release, 2017 01 10;245:95-107.
    PMID: 27889394 DOI: 10.1016/j.jconrel.2016.11.025
    Alzheimer's disease (AD) is a neurodegenerative disease with high prevalence in the rapidly growing elderly population in the developing world. The currently FDA approved drugs for the management of symptomatology of AD are marketed mainly as conventional oral medications. Due to their gastrointestinal side effects and lack of brain targeting, these drugs and dosage regiments hinder patient compliance and lead to treatment discontinuation. Nanotechnology-based drug delivery systems (NTDDS) administered by different routes can be considered as promising tools to improve patient compliance and achieve better therapeutic outcomes. Despite extensive research, literature screening revealed that clinical activities involving NTDDS application in research for AD are lagging compared to NTDDS for other diseases such as cancers. The industrial perspectives, processability, and cost/benefit ratio of using NTDDS for AD treatment are usually overlooked. Moreover, active and passive immunization against AD are by far the mostly studied alternative AD therapies because conventional oral drug therapy is not yielding satisfactorily results. NTDDS of approved drugs appear promising to transform this research from 'paper to clinic' and raise hope for AD sufferers and their caretakers. This review summarizes the recent studies conducted on NTDDS for AD treatment, with a primary focus on the industrial perspectives and processability. Additionally, it highlights the ongoing clinical trials for AD management.
  16. Ichimizu S, Watanabe H, Maeda H, Hamasaki K, Nakamura Y, Chuang VTG, et al.
    J Control Release, 2018 05 10;277:23-34.
    PMID: 29530390 DOI: 10.1016/j.jconrel.2018.02.037
    Human serum albumin (HSA) is a superior carrier for delivering extracellular drugs. However, the development of a cell-penetrating HSA remains a great challenge due to its low membrane permeability. We report herein on the design of a series of palmitoyl-poly-arginine peptides (CPPs) and an evaluation of their cell-penetrating effects after forming a complex with HSA for use in intracellular drug delivery. The palmitoyl CPPs forms a stable complex with HSA by anchoring itself to the high affinity palmitate binding sites of HSA. Among the CPPs evaluated, a cyclic polypeptide composed of D-dodecaarginines, palmitoyl-cyclic-(D-Arg)12 was the most effective for facilitating the cellular uptake of HSA by HeLa cells. Such a superior cell-penetrating capability is primarily mediated by macropinocytosis. The effect of the CPP on pharmacological activity was examined using three drugs loaded in HSA via three different methods: a) an HSA-paclitaxel complex, b) an HSA-doxorubicin covalent conjugate and c) an HSA-thioredoxin fusion protein. The results showed that cell-penetrating efficiency was increased with a corresponding and significant enhancement in pharmacological activity. In conclusion, palmitoyl-cyclic-(D-Arg)12/HSA is a versatile cell-penetrating drug delivery system with great potential for use as a nano-carrier for a wide diversity of pharmaceutical applications.
  17. Beishenaliev A, Loke YL, Goh SJ, Geo HN, Mugila M, Misran M, et al.
    J Control Release, 2023 Jul;359:268-286.
    PMID: 37244297 DOI: 10.1016/j.jconrel.2023.05.032
    Monospecific antibodies have been utilised increasingly for anti-cancer drug targeting owing to their ability to minimise off-target toxicity by binding specifically to a tumour epitope, hence selectively delivering drugs to the tumour cells. Nevertheless, the monospecific antibodies only engage a single cell surface epitope to deliver their drug payload. Hence, their performance is often unsatisfactory in cancers where multiple epitopes need to be engaged for optimal cellular internalisation. In this context, bispecific antibodies (bsAbs) that simultaneously target two distinct antigens or two distinct epitopes of the same antigen offer a promising alternative in antibody-based drug delivery. This review describes the recent advances in developing bsAb-based drug delivery strategies, encompassing the direct conjugation of drug to bsAbs to form bispecific antibody-drug conjugates (bsADCs) and the surface functionalisation of nanoconstructs with bsAbs to form bsAb-coupled nanoconstructs. The article first details the roles of bsAbs in enhancing the internalisation and intracellular trafficking of bsADCs with subsequent release of chemotherapeutic drugs for an augmented therapeutic efficacy, particularly among heterogeneous tumour cell populations. Then, the article discusses the roles of bsAbs in facilitating the delivery of drug-encapsulating nanoconstructs, including organic/inorganic nanoparticles and large bacteria-derived minicells, that provide a larger drug loading capacity and better stability in blood circulation than bsADCs. The limitations of each type of bsAb-based drug delivery strategy and the future prospects of more versatile strategies (e.g., trispecific antibodies, autonomous drug delivery systems, theranostics) are also elaborated.
  18. Anjani QK, Volpe-Zanutto F, Hamid KA, Sabri AHB, Moreno-Castellano N, Gaitán XA, et al.
    J Control Release, 2023 Sep;361:385-401.
    PMID: 37562555 DOI: 10.1016/j.jconrel.2023.08.009
    Malaria is a global parasitic infection that leads to substantial illness and death. The most commonly-used drugs for treatment of malaria vivax are primaquine and chloroquine, but they have limitations, such as poor adherence due to frequent oral administration and gastrointestinal side effects. To overcome these limitations, we have developed nano-sized solid dispersion-based dissolving microarray patches (MAPs) for the intradermal delivery of these drugs. In vitro testing showed that these systems can deliver to skin and receiver compartment up to ≈60% of the payload for CQ-based dissolving MAPs and a total of ≈42% of drug loading for PQ-based dissolving MAPs. MAPs also displayed acceptable biocompatibility in cell tests. Pharmacokinetic studies in rats showed that dissolving MAPs could deliver sustained plasma levels of both PQ and CQ for over 7 days. Efficacy studies in a murine model for malaria showed that mice treated with PQ-MAPs and CQ-MAPs had reduced parasitaemia by up to 99.2%. This pharmaceutical approach may revolutionise malaria vivax treatment, especially in developing countries where the disease is endemic. The development of these dissolving MAPs may overcome issues associated with current pharmacotherapy and improve patient outcomes.
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