Advanced Formulation Approaches for Targeted Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 96912

Special Issue Editors


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Guest Editor
BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, Goyang 10326, Republic of Korea
Interests: organic–inorganic hybrid nanocomposites; oral protein delivery; nanomedicine, targeted drug delivery
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Guest Editor
College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea
Interests: PEGylation; protein stability; nanomedicine; dendrimers; targeted drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Targeted drug delivery is an approach for delivering therapeutics to a patient in a manner that accumulates drugs selectively in the site of action relative to others in the body. The advantages of targeted drug delivery are especially evident in cancer chemotherapy. The selective delivery of cytotoxic drugs to cancer cells allows high local drug concentrations in the target cells while minimizing toxicity to normal cells. Nanoparticles have been one of the main subjects in the area of targeted drug-delivery. Recent advances in nanotechnology facilitate the development of more elaborated targeted-delivery systems for various therapeutics via active targeting or passive targeting.

This Special Issue of Pharmaceutics focuses on new strategies and advanced formulation approaches for targeted drug-delivery including liposomes, polymeric nanoparticles, dendrimers, nanocomposites, and antibody drug conjugates. We welcome articles dealing with all aspects of targeted drug-delivery systems and invite researchers and drug developers to publish their original research or review articles with expert opinions and perspectives in the area of therapeutics.

Prof. Dr. Hyo-Kyung Han
Prof. Dr. Dong Hee Na
Guest Editors

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Keywords

  • targeted drug delivery;
  • nanoparticles;
  • nanomedicine;
  • nanocarriers;
  • liposome;
  • micelles;
  • dendrimers;
  • nanocomposites;
  • antibody–drug conjugates;
  • formulation

Published Papers (14 papers)

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Research

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18 pages, 3353 KiB  
Article
Microencapsulation of Enteric Bacteriophages in a pH-Responsive Solid Oral Dosage Formulation Using a Scalable Membrane Emulsification Process
by Gurinder K. Vinner, Kerry Richards, Miika Leppanen, Antonia P. Sagona and Danish J. Malik
Pharmaceutics 2019, 11(9), 475; https://doi.org/10.3390/pharmaceutics11090475 - 14 Sep 2019
Cited by 50 | Viewed by 6029
Abstract
A scalable low-shear membrane emulsification process was used to produce microencapsulated Escherichia coli-phages in a solid oral dosage form. Uniform pH-responsive composite microparticles (mean size ~100 µm) composed of Eudragit® S100 and alginate were produced. The internal microstructure of the gelled [...] Read more.
A scalable low-shear membrane emulsification process was used to produce microencapsulated Escherichia coli-phages in a solid oral dosage form. Uniform pH-responsive composite microparticles (mean size ~100 µm) composed of Eudragit® S100 and alginate were produced. The internal microstructure of the gelled microcapsules was studied using ion-milling and imaging, which showed that the microparticles had a solid internal core. The microencapsulation process significantly protected phages upon prolonged exposure to a simulated gastric acidic environment. Encapsulated phages that had been pre-exposed to simulated gastric acid were added to actively growing bacterial cells using in vitro cell cultures and were found to be effective in killing E. coli. Encapsulated phages were also shown to be effective in killing actively growing E. coli in the presence of human epithelial cells. Confocal microscopy images showed that the morphology of encapsulated phage-treated epithelial cells was considerably better than controls without phage treatment. The encapsulated phages were stable during refrigerated storage over a four-week period. The process of membrane emulsification is highly scalable and is a promising route to produce industrial quantities of pH-responsive oral solid dosage forms suitable for delivering high titres of viable phages to the gastrointestinal tract. Full article
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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17 pages, 4823 KiB  
Article
Enhanced Subcellular Trafficking of Resveratrol Using Mitochondriotropic Liposomes in Cancer Cells
by Ji Hee Kang and Young Tag Ko
Pharmaceutics 2019, 11(8), 423; https://doi.org/10.3390/pharmaceutics11080423 - 20 Aug 2019
Cited by 38 | Viewed by 5209
Abstract
Mitochondria are membrane-enclosed organelles present in most eukaryotic cells, described as “power houses of the cell”. The mitochondria can be a target for inducing cancer cell death and for developing strategies to bypass multi drug resistance (MDR) mechanisms. 4-Carboxybutyl triphenylphosphonium bromide-polyethylene glycol-distearoylphosphatidylethanolamine (TPP-DSPE-PEG) [...] Read more.
Mitochondria are membrane-enclosed organelles present in most eukaryotic cells, described as “power houses of the cell”. The mitochondria can be a target for inducing cancer cell death and for developing strategies to bypass multi drug resistance (MDR) mechanisms. 4-Carboxybutyl triphenylphosphonium bromide-polyethylene glycol-distearoylphosphatidylethanolamine (TPP-DSPE-PEG) and dequalinium-polyethylene glycol-distearoylphosphatidylethanolamine (DQA-DSPE-PEG) were synthesized as mitochondriotropic molecules. Mitochondria-targeting liposomes carrying resveratrol were constructed by modifying the liposome’s surface with TPP-PEG or DQA-PEG, resulting in TLS (Res) and DLS (Res), respectively, with the aim to obtain longer blood circulation and enhanced permeability and retention (EPR). Both TLS (Res) and DLS (Res) showed dimensions of approximately 120 nm and a slightly positive zeta potential. The enhanced cellular uptake and selective accumulation of TLS (Res) and DLS (Res) into the mitochondria were demonstrated by behavioral observation of rhodamine-labeled TLS or DLS, using confocal microscopy, and by resveratrol quantification in the intracellular organelle, using LC–MS/MS. Furthermore, TLS (Res) and DLS (Res) induced cytotoxicity of cancer cells by generating reactive oxygen species (ROS) and by dissipating the mitochondrial membrane potential. Our results demonstrated that TLS (Res) and DLS (Res) could provide a potential strategy to treat cancers by mitochondrial targeting delivery of therapeutics and stimulation of the mitochondrial signaling pathway. Full article
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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16 pages, 5435 KiB  
Article
Potential Albumin-Based Antioxidant Nanoformulations for Ocular Protection against Oxidative Stress
by Daseul Kim, Pooja Maharjan, Minki Jin, Taehoon Park, Anjila Maharjan, Reeju Amatya, JaeWook Yang, Kyoung Ah Min and Meong Cheol Shin
Pharmaceutics 2019, 11(7), 297; https://doi.org/10.3390/pharmaceutics11070297 - 26 Jun 2019
Cited by 39 | Viewed by 3446
Abstract
Amongst various drug administration methods, ophthalmic drug delivery has been a useful way for the treatment of eye-related diseases. However, therapeutic efficacy of ocular therapy for anterior or posterior eye segments through topical administration is considerably challenged by the number of anatomical and [...] Read more.
Amongst various drug administration methods, ophthalmic drug delivery has been a useful way for the treatment of eye-related diseases. However, therapeutic efficacy of ocular therapy for anterior or posterior eye segments through topical administration is considerably challenged by the number of anatomical and physiological barriers in the eyes affecting ocular bioavailability. In this respect, advanced biocompatible nanoformulations make it possible to improve drug delivery to the target sites and enhance ocular bioavailability of ophthalmic medicines. Various ocular diseases have been reported to be related to oxidative stresses in tissues, and polyphenolic compounds have been known for their antioxidant activities in various tissues, including the eyes. Despite drug efficacy, poor water solubility and intrinsic color of the compounds limit the drug’s inclusion into the development of ocular medicine. In the present study, we investigated the antioxidant protectant efficacy of rosmarinic or ursolic acid in the retinal epithelial cells, as compared to those of curcumin, by forming nanospheres with bovine serum albumin. Our results demonstrate that antioxidant-containing nanoformulations provide a significantly higher drug solubility and decreased ROS (reactive oxygen species) production in the retinal epithelial cells. Finally, we also found that albumin-based nanoformulations could improve bioavailability and increase antioxidant activity of rosmarinic or ursolic acid in the retina to be applied as efficient ocular protectant. Full article
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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12 pages, 2272 KiB  
Article
Co-delivery of D-(KLAKLAK)2 Peptide and Chlorin e6 using a Liposomal Complex for Synergistic Cancer Therapy
by Chaemin Lim, Jin Kook Kang, Woong Roeck Won, June Yong Park, Sang Myung Han, Thi ngoc Le, Jae Chang Kim, Jaewon Her, Yuseon Shin and Kyung Taek Oh
Pharmaceutics 2019, 11(6), 293; https://doi.org/10.3390/pharmaceutics11060293 - 21 Jun 2019
Cited by 14 | Viewed by 3891
Abstract
Nanotechnology-based photo-chemo combination therapy has been extensively investigated to improve therapeutic outcomes in anticancer treatment. Specifically, with the help of a singlet oxygen generated by the photosensitizer, the endocytosed nanoparticles are allowed to escape from the endosomal compartment, which is currently an obstacle [...] Read more.
Nanotechnology-based photo-chemo combination therapy has been extensively investigated to improve therapeutic outcomes in anticancer treatment. Specifically, with the help of a singlet oxygen generated by the photosensitizer, the endocytosed nanoparticles are allowed to escape from the endosomal compartment, which is currently an obstacle in nanotechnology-based anticancer therapy. In this study, a liposomal complex system (Lipo (Pep, Ce6)), composed of a chlorin e6-conjugated di-block copolymer (PEG-PLL(-g-Ce6)) and a D-(KLAKLAK)2 peptide loading liposome (Lipo (Pep)), was developed and evaluated for its anticancer activity. Due to the membrane lytic ability of the D-(KLAKLAK)2 peptide and the membrane disruptive effect of the singlet oxygen generated from chlorin e6, Lipo (Pep, Ce6) accelerated the disruption of the endosomal compartment, and exhibited strong synergistic anticancer activity in vitro. The prepared liposomal complex system could potentially maximize the efficacy of the nanotechnology-based photo-chemo combination therapy, and can be regarded as a novel, versatile strategy in advanced tumor therapy. Full article
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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17 pages, 2396 KiB  
Article
Optimization of Polyarginine-Conjugated PEG Lipid Grafted Proliposome Formulation for Enhanced Cellular Association of a Protein Drug
by Amolnat Tunsirikongkon, Yong-Chul Pyo, Dong-Hyun Kim, Sang-Eun Lee and Jeong-Sook Park
Pharmaceutics 2019, 11(6), 272; https://doi.org/10.3390/pharmaceutics11060272 - 11 Jun 2019
Cited by 15 | Viewed by 3771
Abstract
The purpose of this study was to develop an oral proliposomal powder of protein using poly-l-arginine-conjugated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG) (PLD) for enhancing cellular association upon reconstitution and to compare its effects with a non-grafted and PEGylated formulation. Cationic proliposome (CATL), PLD-grafted [...] Read more.
The purpose of this study was to develop an oral proliposomal powder of protein using poly-l-arginine-conjugated 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG) (PLD) for enhancing cellular association upon reconstitution and to compare its effects with a non-grafted and PEGylated formulation. Cationic proliposome (CATL), PLD-grafted CATL (PLD-CATL), PEGylated CATL (PEG CATL), and PLD grafted-PEG CATL (PLD-PEG CATL) were prepared and compared. Successful conjugation between poly-l-arginine and DSPE-PEG was confirmed by 1H NMR and FT-IR. PLD was successfully grafted onto the proliposomal powder during the slurry process. Although reconstituted liposomal sizes of CATL and PLD-CATL were increased by agglomeration, PEGylation reduced the agglomeration and increased the encapsulation. The viabilities of cells treated with both CATL and PLD-CATL formulations were low but increased following PEGylation. With regard to cellular association, PLD-CATL enhanced cellular association/uptake more rapidly than did CATL. Upon PEGylation, PEG CATL showed a lower level of cellular association/uptake compared with CATL while PLD-PEG CATL did not exhibit the rapid cellular association/uptake as seen with PLD-CATL. However, PLD-PEG CATL still enhanced the higher cellular association/uptake than PEG CATL did without PLD. In conclusion, proliposomes with PLD could accelerate cellular association/uptake but also caused high cellular toxicity. PEGylation reduced cellular toxicity and also changed the cellular association pattern of the PLD formulation. Full article
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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17 pages, 4116 KiB  
Article
Bacteria-Targeted Clindamycin Loaded Polymeric Nanoparticles: Effect of Surface Charge on Nanoparticle Adhesion to MRSA, Antibacterial Activity, and Wound Healing
by Nurhasni Hasan, Jiafu Cao, Juho Lee, Shwe Phyu Hlaing, Murtada A. Oshi, Muhammad Naeem, Min-Hyo Ki, Bok Luel Lee, Yunjin Jung and Jin-Wook Yoo
Pharmaceutics 2019, 11(5), 236; https://doi.org/10.3390/pharmaceutics11050236 - 15 May 2019
Cited by 70 | Viewed by 5848
Abstract
Adhesion of nanoparticles (NPs) to the bacterial cell wall by modifying their physicochemical properties can improve the antibacterial activity of antibiotic. In this study, we prepared positively charged clindamycin-loaded poly (lactic-co-glycolic acid)-polyethylenimine (PLGA-PEI) nanoparticles (Cly/PPNPs) and negatively charged clindamycin-loaded PLGA NPs [...] Read more.
Adhesion of nanoparticles (NPs) to the bacterial cell wall by modifying their physicochemical properties can improve the antibacterial activity of antibiotic. In this study, we prepared positively charged clindamycin-loaded poly (lactic-co-glycolic acid)-polyethylenimine (PLGA-PEI) nanoparticles (Cly/PPNPs) and negatively charged clindamycin-loaded PLGA NPs (Cly/PNPs) and investigated the effect of NP adhesion to bacteria on the treatment of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. The Cly/PPNPs and Cly/PNPs were characterized according to particle size, polydispersity index, surface charge, and drug loading. Both Cly/PPNPs and Cly/PNPs exhibited sustained drug release over 2 days. The Cly/PPNPs bind to the MRSA surface, thereby enhancing bactericidal efficacy against MRSA compared with the Cly/PNPs. Furthermore, compared with other groups, Cly/PPNPs significantly accelerated the healing and re-epithelialization of wounds in a mouse model of a MRSA-infected wounds. We also found that both NPs are harmless to healthy fibroblast cells. Therefore, our results suggest that the Cly/PPNPs developed in this study improve the efficacy of clindamycin for the treatment of MRSA-infected wounds. Full article
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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17 pages, 5273 KiB  
Article
Transferrin-Conjugated Polymeric Nanoparticle for Receptor-Mediated Delivery of Doxorubicin in Doxorubicin-Resistant Breast Cancer Cells
by Zar Chi Soe, Jun Bum Kwon, Raj Kumar Thapa, Wenquan Ou, Hanh Thuy Nguyen, Milan Gautam, Kyung Taek Oh, Han-Gon Choi, Sae Kwang Ku, Chul Soon Yong and Jong Oh Kim
Pharmaceutics 2019, 11(2), 63; https://doi.org/10.3390/pharmaceutics11020063 - 01 Feb 2019
Cited by 81 | Viewed by 7182
Abstract
In this study, a transferrin (Tf)-conjugated polymeric nanoparticle was developed for the targeted delivery of the chemotherapeutic agent doxorubicin (Dox) in order to overcome multi-drug resistance in cancer treatment. Our objective was to improve Dox delivery for producing significant antitumor efficacy [...] Read more.
In this study, a transferrin (Tf)-conjugated polymeric nanoparticle was developed for the targeted delivery of the chemotherapeutic agent doxorubicin (Dox) in order to overcome multi-drug resistance in cancer treatment. Our objective was to improve Dox delivery for producing significant antitumor efficacy in Dox-resistant (R) breast cancer cell lines with minimum toxicity to healthy cells. The results of our experiments revealed that Dox was successfully loaded inside a transferrin (Tf)-conjugated polymeric nanoparticle composed of poloxamer 407 (F127) and 123 (P123) (Dox/F127&P123-Tf), which produced nanosized particles (~90 nm) with a low polydispersity index (~0.23). The accelerated and controlled release profiles of Dox from the nanoparticles were characterized in acidic and physiological pH and Dox/F127&P123-Tf enhanced Dox cytotoxicity in OVCAR-3, MDA-MB-231, and MDA-MB-231(R) cell lines through induction of cellular apoptosis. Moreover, Dox/F127&P123-Tf inhibited cell migration and altered the cell cycle patterns of different cancer cells. In vivo study in MDA-MB-231(R) tumor-bearing mice demonstrated enhanced delivery of nanoparticles to the tumor site when coated in a targeting moiety. Therefore, Dox/F127&P123-Tf has been tailored, using the principles of nanotherapeutics, to overcome drug-resistant chemotherapy. Full article
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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13 pages, 6497 KiB  
Article
Dendritic Cell-Targeted pH-Responsive Extracellular Vesicles for Anticancer Vaccination
by Hyuk Lee, Hongsuk Park, Hyeong Sup Yu, Kun Na, Kyung Taek Oh and Eun Seong Lee
Pharmaceutics 2019, 11(2), 54; https://doi.org/10.3390/pharmaceutics11020054 - 27 Jan 2019
Cited by 27 | Viewed by 4124
Abstract
Immunotherapy can potentially treat cancers on a patient-dependent manner. Most of the efforts expended on anticancer vaccination parallel the efforts expended on prototypical immunization in infectious diseases. In this study, we designed and synthesized pH-responsive extracellular vesicles (EVs) coupled with hyaluronic acid (HA), [...] Read more.
Immunotherapy can potentially treat cancers on a patient-dependent manner. Most of the efforts expended on anticancer vaccination parallel the efforts expended on prototypical immunization in infectious diseases. In this study, we designed and synthesized pH-responsive extracellular vesicles (EVs) coupled with hyaluronic acid (HA), 3-(diethylamino)propylamine (DEAP), monophosphoryl lipid A (MPLA), and mucin 1 peptide (MUC1), referred to as HDEA@EVAT. HDEA@EVAT potentiated the differentiation and maturation of monocytes into dendritic cells (DCs) and the priming of CD8+ T-cells for cancer therapy. MPLA and HA enabled HDEA@EVAT to interact with the toll-like receptor 4 and the CD44 receptor on DCs, followed by endosomal escape, owing to the protonation of pH-sensitive DEAP on the EV in conjunction with MUC1 release. The MUC1 was then processed and presented to DCs to activate CD8+ T-cells for additional anticancer-related immune reactions. Our findings support the anticancer vaccine activity by which HDEA@EVAT expedites the interaction between DCs and CD8+ T-cells by inducing DC-targeted maturation and by presenting the cancer-associated peptide MUC1. Full article
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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Review

Jump to: Research

24 pages, 1013 KiB  
Review
Polymer-Drug Conjugate, a Potential Therapeutic to Combat Breast and Lung Cancer
by Sibusiso Alven, Xhamla Nqoro, Buhle Buyana and Blessing A. Aderibigbe
Pharmaceutics 2020, 12(5), 406; https://doi.org/10.3390/pharmaceutics12050406 - 29 Apr 2020
Cited by 65 | Viewed by 4202
Abstract
Cancer is a chronic disease that is responsible for the high death rate, globally. The administration of anticancer drugs is one crucial approach that is employed for the treatment of cancer, although its therapeutic status is not presently satisfactory. The anticancer drugs are [...] Read more.
Cancer is a chronic disease that is responsible for the high death rate, globally. The administration of anticancer drugs is one crucial approach that is employed for the treatment of cancer, although its therapeutic status is not presently satisfactory. The anticancer drugs are limited pharmacologically, resulting from the serious side effects, which could be life-threatening. Polymer drug conjugates, nano-based drug delivery systems can be utilized to protect normal body tissues from the adverse side effects of anticancer drugs and also to overcome drug resistance. They transport therapeutic agents to the target cell/tissue. This review article is based on the therapeutic outcomes of polymer-drug conjugates against breast and lung cancer. Full article
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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20 pages, 1492 KiB  
Review
Strategic Approaches for Colon Targeted Drug Delivery: An Overview of Recent Advancements
by Sang Hoon Lee, Rajiv Bajracharya, Jeong Youn Min, Ji-Won Han, Byeong Ju Park and Hyo-Kyung Han
Pharmaceutics 2020, 12(1), 68; https://doi.org/10.3390/pharmaceutics12010068 - 15 Jan 2020
Cited by 146 | Viewed by 17920
Abstract
Colon targeted drug delivery systems have gained a great deal of attention as potential carriers for the local treatment of colonic diseases with reduced systemic side effects and also for the enhanced oral delivery of various therapeutics vulnerable to acidic and enzymatic degradation [...] Read more.
Colon targeted drug delivery systems have gained a great deal of attention as potential carriers for the local treatment of colonic diseases with reduced systemic side effects and also for the enhanced oral delivery of various therapeutics vulnerable to acidic and enzymatic degradation in the upper gastrointestinal tract. In recent years, the global pharmaceutical market for biologics has grown, and increasing demand for a more patient-friendly drug administration system highlights the importance of colonic drug delivery as a noninvasive delivery approach for macromolecules. Colon-targeted drug delivery systems for macromolecules can provide therapeutic benefits including better patient compliance (because they are pain-free and can be self-administered) and lower costs. Therefore, to achieve more efficient colonic drug delivery for local or systemic drug effects, various strategies have been explored including pH-dependent systems, enzyme-triggered systems, receptor-mediated systems, and magnetically-driven systems. In this review, recent advancements in various approaches for designing colon targeted drug delivery systems and their pharmaceutical applications are covered with a particular emphasis on formulation technologies. Full article
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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27 pages, 3889 KiB  
Review
Active Cellular and Subcellular Targeting of Nanoparticles for Drug Delivery
by Okhil K. Nag and James B. Delehanty
Pharmaceutics 2019, 11(10), 543; https://doi.org/10.3390/pharmaceutics11100543 - 18 Oct 2019
Cited by 69 | Viewed by 6300
Abstract
Nanoparticle (NP)-mediated drug delivery (NMDD) for active targeting of diseases is a primary goal of nanomedicine. NPs have much to offer in overcoming the limitations of traditional drug delivery approaches, including off-target drug toxicity and the need for the administration of repetitive doses. [...] Read more.
Nanoparticle (NP)-mediated drug delivery (NMDD) for active targeting of diseases is a primary goal of nanomedicine. NPs have much to offer in overcoming the limitations of traditional drug delivery approaches, including off-target drug toxicity and the need for the administration of repetitive doses. In the last decade, one of the main foci in NMDD has been the realization of NP-mediated drug formulations for active targeted delivery to diseased tissues, with an emphasis on cellular and subcellular targeting. Advances on this front have included the intricate design of targeted NP-drug constructs to navigate through biological barriers, overcome multidrug resistance (MDR), decrease side effects, and improve overall drug efficacy. In this review, we survey advancements in NP-mediated drug targeting over the last five years, highlighting how various NP-drug constructs have been designed to achieve active targeted delivery and improved therapeutic outcomes for critical diseases including cancer, rheumatoid arthritis, and Alzheimer’s disease. We conclude with a survey of the current clinical trial landscape for active targeted NP-drug delivery and how we envision this field will progress in the near future. Full article
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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18 pages, 953 KiB  
Review
Liposomal Formulations for Nose-to-Brain Delivery: Recent Advances and Future Perspectives
by Soon-Seok Hong, Kyung Taek Oh, Han-Gon Choi and Soo-Jeong Lim
Pharmaceutics 2019, 11(10), 540; https://doi.org/10.3390/pharmaceutics11100540 - 17 Oct 2019
Cited by 103 | Viewed by 10361
Abstract
Restricted drug entry to the brain that is closely associated with the existence of the blood brain barrier (BBB) has limited the accessibility of most potential active therapeutic compounds to the brain from the systemic circulation. Recently, evidences for the presence of direct [...] Read more.
Restricted drug entry to the brain that is closely associated with the existence of the blood brain barrier (BBB) has limited the accessibility of most potential active therapeutic compounds to the brain from the systemic circulation. Recently, evidences for the presence of direct nose-to-brain drug transport pathways have been accumulated by several studies and an intranasal drug administration route has gained attention as a promising way for providing direct access to the brain without the needs to cross to the BBB. Studies aiming for developing nanoparticles as an intranasal drug carrier have shown considerable promise in overcoming the challenges of intranasal drug delivery route. This review gives a comprehensive overview of works having investigated liposomes as a potential vehicle to deliver drugs to the brain through nose-to-brain route while considering the excellent biocompatibility and high potential of liposomes for clinical development. Herein, studies are reviewed with special emphasis on the impact of formulation factors, such as liposome composition and surface modification of liposomes with targeting moieties, in addition to intranasal environmental factors that may affect the extent/site of absorption of intranasally administered, liposome-encapsulated drugs. Full article
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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29 pages, 538 KiB  
Review
Advanced Formulation Approaches for Ocular Drug Delivery: State-Of-The-Art and Recent Patents
by Eliana B. Souto, João Dias-Ferreira, Ana López-Machado, Miren Ettcheto, Amanda Cano, Antonio Camins Espuny, Marta Espina, Maria Luisa Garcia and Elena Sánchez-López
Pharmaceutics 2019, 11(9), 460; https://doi.org/10.3390/pharmaceutics11090460 - 06 Sep 2019
Cited by 115 | Viewed by 10614
Abstract
The eye presents extensive perspectives and challenges for drug delivery, mainly because of the extraordinary capacity, intrinsic to this path, for drugs to permeate into the main circulatory system and also for the restrictions of the ocular barriers. Depending on the target segment [...] Read more.
The eye presents extensive perspectives and challenges for drug delivery, mainly because of the extraordinary capacity, intrinsic to this path, for drugs to permeate into the main circulatory system and also for the restrictions of the ocular barriers. Depending on the target segment of the eye, anterior or posterior, the specifications are different. The ocular route experienced in the last decades a lot of progresses related with the development of new drugs, improved formulations, specific-designed delivery and even new routes to administer a drug. Concomitantly, new categories of materials were developed and adapted to encapsulate drugs. With such advances, a multiplicity of parameters became possible to be optimized as the increase in bioavailability and decreased toxic effects of medicines. Also, the formulations were capable to easily adhere to specific tissues, increase the duration of the therapeutic effect and even target the delivery of the treatment. The ascending of new delivery systems for ocular targeting is a current focus, mainly because of the capacity to extend the normal time during which the drug exerts its therapeutic effect and, so, supplying the patients with a product which gives them fewer side effects, fewer number of applications and even more effective outcomes to their pathologies, surpassing the traditionally-used eye drops. Depending on the systems, some are capable of increasing the duration of the drug action as gels, emulsions, prodrugs, liposomes, and ocular inserts with hydrophilic properties, improving the absorption by the cornea. In parallel, other devices use as a strategy the capacity to sustain the release of the carried drugs by means of erodible and non-erodible matrices. This review discusses the different types of advanced formulations used for ocular delivery of therapeutics presenting the most recent patents according to the clinical applications. Full article
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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28 pages, 2242 KiB  
Review
Recent Progress in the Development of Poly(lactic-co-glycolic acid)-Based Nanostructures for Cancer Imaging and Therapy
by Ki-Taek Kim, Jae-Young Lee, Dae-Duk Kim, In-Soo Yoon and Hyun-Jong Cho
Pharmaceutics 2019, 11(6), 280; https://doi.org/10.3390/pharmaceutics11060280 - 14 Jun 2019
Cited by 75 | Viewed by 6273
Abstract
Diverse nanosystems for use in cancer imaging and therapy have been designed and their clinical applications have been assessed. Among a variety of materials available to fabricate nanosystems, poly(lactic-co-glycolic acid) (PLGA) has been widely used due to its biocompatibility and biodegradability. [...] Read more.
Diverse nanosystems for use in cancer imaging and therapy have been designed and their clinical applications have been assessed. Among a variety of materials available to fabricate nanosystems, poly(lactic-co-glycolic acid) (PLGA) has been widely used due to its biocompatibility and biodegradability. In order to provide tumor-targeting and diagnostic properties, PLGA or PLGA nanoparticles (NPs) can be modified with other functional materials. Hydrophobic or hydrophilic therapeutic cargos can be placed in the internal space or adsorbed onto the surface of PLGA NPs. Protocols for the fabrication of PLGA-based NPs for cancer imaging and therapy are already well established. Moreover, the biocompatibility and biodegradability of PLGA may elevate its feasibility for clinical application in injection formulations. Size-controlled NP’s properties and ligand–receptor interactions may provide passive and active tumor-targeting abilities, respectively, after intravenous administration. Additionally, the introduction of several imaging modalities to PLGA-based NPs can enable drug delivery guided by in vivo imaging. Versatile platform technology of PLGA-based NPs can be applied to the delivery of small chemicals, peptides, proteins, and nucleic acids for use in cancer therapy. This review describes recent findings and insights into the development of tumor-targeted PLGA-based NPs for use of cancer imaging and therapy. Full article
(This article belongs to the Special Issue Advanced Formulation Approaches for Targeted Drug Delivery)
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