Sustained and targeted delivery of hydrophilic drug compounds: A review of existing and novel technologies from bench to bedside

Hawthorne, D.; Pannala, Ananth Sekher; Sandeman, Susan; Lloyd, Andrew W.

doi:10.1016/j.jddst.2022.103936

Cited by 20 publications

(12 citation statements)

References 215 publications

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“…[96] In contrast, excessive hydrophilicity may not be conducive to biological applications. [97] For example, oseltamivir carboxylate is a drug [92] Copyright 2017, Royal Society of Chemistry. c) Chemical structure of TPE-R-DNA; d) confocal image of mRNA in MCF-7 cells treated with 10 μg mL À1 lipopolysaccharide (LPS) for 2 h and then incubated with TPE-R-DNA (6.6 μM) and Exo III (1.33 U mL À1 ) for 1 h under the standard cell culture conditions; e) PL intensity of renal cancer and its adjacent tissue; f ) Kaplan-Meier survival curves of patients categorized into high-and lowexpression groups based on the MnSOD mRNA signature.…”

Section: Discussionmentioning

confidence: 99%

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Water‐Soluble Aggregation‐Induced Emission Luminogens with Near‐Infrared Emission for Advanced Phototheranostics

Shen

et al. 2023

Small Science

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The development of water‐soluble aggregation‐induced emission luminogens (AIEgens) emitting in the near‐infrared (NIR) window holds promise for efficient biomedical applications. Nevertheless, synthesizing water‐soluble counterparts of NIR AIEgens presents difficulties due to their intrinsic hydrophobic properties. To address this issue, researchers have developed various molecular design strategies to improve the water solubility of NIR AIEgens. The integration of hydrophilic groups and targeting moieties is a crucial aspect of achieving precise phototheranostics. Here, diverse approaches to attain water‐soluble NIR AIEgens for biomedical applications are presented, and three commonly used strategies that involve decorating NIR AIEgens with positively or negatively charged groups, hydrophilic chains, and bioactive moieties are elaborated. These rational design strategies are believed to provide solutions for enhancing the water solubility and biological performance of NIR AIEgens in a single action. The remaining challenges and opportunities in this field are also discussed. The aim is to provide new insights into the design of water‐soluble NIR AIEgens and inspire more researchers to make significant contributions to this promising research area.

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Section: Discussionmentioning

confidence: 99%

“…[ 96 ] In contrast, excessive hydrophilicity may not be conducive to biological applications. [ 97 ] For example, oseltamivir carboxylate is a drug that selectively inhibits the neuraminidase of influenza viruses A and B. However, because the carboxylate structure is too hydrophilic, its oral bioavailability is only 5% in humans.…”

Section: Discussionmentioning

confidence: 99%

Water‐Soluble Aggregation‐Induced Emission Luminogens with Near‐Infrared Emission for Advanced Phototheranostics

Shen

et al. 2023

Small Science

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“…In addition, the hydrogels have been shown to be suitable polymeric vehicles for hydrophilic drug delivery because of their high water content and low leakage; dissolved medications can be ensnared in the aqueous nodes of the swollen cross-linked polymer matrix (68). Some of the hydrophilic drugs loaded into the hydrogel include metformin (69) and chemotheraputic agents such as 5-fluorouracil (70) and tamoxifen citrate (71).…”

Section: Discussionmentioning

confidence: 99%

Design and optimization of thermosensitive injectable alginate-based hydrogels: potential for loading therapeutic compounds

Hasannejad

Arab

Farahmand

et al. 2023

Preprint

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Injectable hydrogels with high biocompatibility and easy fabrication have numerous advantages over other drug delivery systems. These can be readily injected at the tumor site, causing high loads of drugs entrapped within their structures. The aim of the present study, therefore, was to prepare an optimal formulation of alginate-based hydrogels to be thermosensitive and injectable for loading therapeutic agents and drug delivery. Here, four constituents including hydroxypropyl methylcellulose (HPMC), sodium alginate (SA), beta-glycerol phosphate (β-GP), and calcium chloride (CaCl2) were used to obtain the optimal formulations. A surface response methodology (RSM), namely Box-Behnken, in the design of experiment (DOE), was employed. DOE identified 27 hydrogels, which were synthesized accordingly. Based on the gelation temperature (as an objective function), two optimal hydrogel formulations were predicted by DOE and prepared for further analysis. Rheological tests, ART-FTIR, FE-SEM, biodegradability, swelling (at PH = 7.45 and PH = 6.5), and hydrogel biocompatibility to L929 cells (staining of Dihydroetidium (DHE), Phaloidine, and Acridine Orange (AO)) were performed. Furthermore, to demonstrate the potential of the optimum hydrogels for carrying and releasing therapeutic agents, menstrual blood-derived mesenchymal stem cells exosomes (Mens-exo) were used as a model drug, and their release rate and hydrogel degradability were evaluated. The results showed that all the constituents in the hydrogels except for HPMC had significant effects on the gelling process (temperature). The two hydrogel formulations with gelling temperatures of 35° C (H1) and 37° C (H2) were selected for relevant tests. ATR-FTIR and FE-SEM analyses indicated the suitability of chemical and morphological characteristics of both hydrogel samples. The obtained storage modulus (G ') and loss modulus (G″) for gelling temperature and time, strain and frequency tests showed that H1 hydrogel has more favorable rheological properties. Furthermore, in the evaluation of degradability at PH = 6.5, H1 hydrogel was degraded in a longer time (154 hours) and was more stable than H2 (100 hours). The cells loaded in the hydrogels also indicated the superior biocompatibility of H1 hydrogel rather than the H2. Moreover, the Mens-exo loading in H1 hydrogel exhibited a sustained release with reasonable degradability of the hydrogel. The results showed that the optimal hydrogels made up of HPMC, SA, β-GP, and CaCl2 were thermosensitive and injectable. In particular, the H1 hydrogel (SA = 0.889, HPMC = 2, β-GP = 5 and CaCl2 = 3.306) had high potential for loading therapeutic compounds.

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“…Hydrophobic groups, such as alkyl chains, can improve the solubility and stability of drugs, enabling their effective delivery to the target site. 9 In contrast, hydrophilic groups, such as carboxylic acids or polyethylene glycol (PEG), can improve the bioavailability and reduce the toxicity of drugs by increasing their water solubility and preventing degradation in the bloodstream. [9][10][11] S C H E M E 1 Synthetic procedure of PBLA through the PBLA aminolysis reaction.…”

Section: Introductionmentioning

confidence: 99%

“…Hydrophobic and hydrophilic moieties are crucial components in designing efficient drug delivery systems. Hydrophobic groups, such as alkyl chains, can improve the solubility and stability of drugs, enabling their effective delivery to the target site 9 . In contrast, hydrophilic groups, such as carboxylic acids or polyethylene glycol (PEG), can improve the bioavailability and reduce the toxicity of drugs by increasing their water solubility and preventing degradation in the bloodstream 9–11 …”

Section: Introductionmentioning

confidence: 99%

Synthesis of alternating copolymer PAspNa‐alt‐PAsp(Pr) for drug delivery system

Mai,

Vy,

Duong

2024

Vietnam Journal of Chemistry

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Alternating copolymers (ACs) contain two distinct monomeric unit types dispersed in alternating order of hydrophilic block and hydrophobic block. ACs have extensive and versatile applications in both academia and industry, especially in drug delivery systems (DDS) due to their unique physical and chemical properties. In the present research, poly(β‐benzyl l‐aspartate) (PBLA) was prepared by ring‐opening polymerization of BLA‐NCA. The result obtained from GPC showed that PBLA was successfully synthesized with narrow weight distribution Mw/Mn = 1.055. The outcome of copolymer has the degree of polymerization (DP) of PBLA was 50 based on the 1H NMR spectroscopy. Further, alternating copolymer poly(aspartate‐sodium) alternating poly(aspartate‐R) (PAspNa‐alt‐PAsp(Pr)), which allows the installation of expected compounds into a polymer backbone of PBLA without unwanted side effects, was synthesized via 2 steps: (1) aminolysis by 0.5 fold primary amine to attach hydrophobic group and (2) hydrolysis slowly by NaOH solution to form the hydrophilic group on the side chain of the polymer. The novel alternating copolymer synthesized successfully in this study was expected to be a promising candidate for drug delivery devices.

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Sustained and targeted delivery of hydrophilic drug compounds: A review of existing and novel technologies from bench to bedside

Cited by 20 publications

References 215 publications

Water‐Soluble Aggregation‐Induced Emission Luminogens with Near‐Infrared Emission for Advanced Phototheranostics

Water‐Soluble Aggregation‐Induced Emission Luminogens with Near‐Infrared Emission for Advanced Phototheranostics

Design and optimization of thermosensitive injectable alginate-based hydrogels: potential for loading therapeutic compounds

Synthesis of alternating copolymer PAspNa‐alt‐PAsp(Pr) for drug delivery system

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