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Innovations in vaccine delivery: increasing access, coverage, and equity and lessons learnt from measles and rubella elimination
James L. Goodson & Paul A. Rota
doi : 10.1007/s13346-022-01130-9
Volume 12, issue 5, May 2022
Disease eradication and elimination programs drive innovations based on progress toward measurable objectives, evaluations of new strategies and methods, programmatic experiences, and lessons learned from the field. Following progress toward global measles elimination, reducing measles mortality, and increasing introductions of measles and rubella vaccines to national programs, the measles and rubella immunization program has faced setbacks in recent years. Currently available vaccine delivery methods have complicated logistics and drawbacks that create barriers to vaccination; innovations for easier, more efficient, and safer vaccine delivery are needed. Progress can be accelerated by new technologies like microarray patches (MAPs) that are now widely recognized as a potential new tool for enhancing global immunizations efforts. Clinical trials of measles-rubella vaccine MAPs have begun, and several other vaccine MAPs are in the pre-clinical development pathway. MAPs could significantly contribute to Immunization Agenda 2030 priorities, including reaching zero-dose children; increasing vaccine access, demand, coverage, and equity; and achieving measles and rubella elimination. With strong partnerships between public health agencies and biotechnology companies, translational novel vaccine delivery systems can be developed to help solve public health problems and achieve global health priorities.
Mucosal and transdermal vaccine delivery strategies against COVID-19
Ashwini Kumar & Awanish Kumar
doi : 10.1007/s13346-021-01001-9
The years 2020 and 2021 have witnessed a COVID-19 pandemic caused by the SARS-CoV-2 virus. However, these years have also witnessed certain remarkable scientific achievements. Researchers across the globe have been trying extremely hard and accomplished in bringing vaccines a great variety of COVID-19 vaccines. Though the route of administration for the majority of these vaccines has been the intramuscular route (invasive), some laboratories are developing formulations intended for transmucosal and transcutaneous (non-invasive) administration, which are in the early phases of pre-clinical and clinical development. This short report discusses these unconventional formulations against COVID-19, in brief, to stress the importance of research in the field of drug delivery.
Design and development of insulin microneedles for diabetes treatment
Qida Zong, Ranran Guo, Naijun Dong, Guixia Ling & Peng Zhang
doi : 10.1007/s13346-021-00981-y
As a painless and minimally invasive method of self-administration, microneedle is very promising to replace subcutaneous injection of insulin for type I diabetes treatment. Since the introduction of microneedles, many scholars have paid attention to and studied this technology, which has made it developed rapidly. However, there is no product on the market or in clinical trials at present. The reason is that there are still many technical problems in microneedle drug delivery system, such as the perfect integration of stable, controllable, fast, long-lasting, safe, and other necessary conditions. Here, we review the achievements that researchers have made that contain one or more of the above factors, and put some ideas to solve the limitations of insulin delivery by microneedles for reference.
Topical delivery of salicylates
Soo Chin Yeoh & Choon Fu Goh
doi : 10.1007/s13346-021-00988-5
Salicylates have a long history of use for pain relief. Salicylic acid and methyl salicylate are among the widely used topical salicylates namely for keratolytic and anti-inflammatory actions, respectively. The current review summarises both passive and active strategies, including emerging technologies employed to enhance skin permeation of these two salicylate compounds. The formulation design of topical salicylic acid targets the drug retention in and on the skin based on the different indications including keratolytic, antibacterial and photoprotective actions, while the investigations of topical delivery strategies for methyl salicylate are limited. The pharmacokinetics and metabolisms of both salicylate compounds are discussed. The current overview and future perspectives of the topical delivery strategies are also highlighted for translational considerations of formulation designs.
Extension in the approaches to treat cancer through siRNA system: a beacon of hope in cancer therapy
Indra Rautela, Aditi Sharma, Pallavi Dheer, Priya Thapliyal, Shweta Sahni, Vimlendu Bhushan Sinha & Manish Dev Sharma
doi : 10.1007/s13346-021-00995-6
Along with the evolutionary breakthrough of RNA interference and the applicability for gene knockdown, a subsequent development in siRNA-based therapeutics has been attained. The gene therapy based on RNAi is in transition progress from the research aspects to clinical base. Being a potent tool, siRNA is used as therapeutic against several disorders. Cancer which is one of the deadliest diseases is now treated with an advanced mechanism of siRNA delivery inside the genome, leading to gene silencing; thereby, blocking translation of gene to form protein. siRNA tool delivers remedial effects with the advantages of safe delivery and efficiency. Despite its merits, barriers including instability at physiological conditions, lack of ability to cross biological membranes, off-targets, and safety are also associated with siRNA delivery system. The gene silencing efficiency values both in vitro and in vivo reported in the past years have been reviewed by material type (lipid, polymer, silica, porous silicon, and metal). This review presents a deep insight in the development of targeted delivery of siRNA. Since several clinical trials have also been performed regarding the siRNA delivery against cancer, it can also be stated that the delivery system should be good enough to achieve effective siRNA drug development.
Nanodiamonds and their potential applications in breast cancer therapy: a narrative review
Kenny Tjo & Pegah Varamini
doi : 10.1007/s13346-021-00996-5
Breast cancer remains the most commonly diagnosed cancer and the leading cause of cancer-related death among women worldwide. With the projected increase in breast cancer cases in recent years, optimising treatment becomes increasingly important. Current treatment modalities in breast cancer present major limitations, including chemoresistance, dose-limiting adverse effects and lack of selectivity in aggressive subtypes of breast cancers such as triple-negative breast cancer. Nanodiamonds have demonstrated promising outcomes in preclinical models from their unique surface characteristics allowing optimised delivery of various therapeutic agents, overcoming some of the significant hurdles in conventional treatment modalities. This review will present an update on preclinical findings of nanodiamond-based drug delivery systems for breast cancer therapy to date, challenges with the use of nanodiamonds along with considerations for future research.
MicroRNAs as therapeutic targets in breast cancer metastasis
Fahima Danesh Pouya, Yousef Rasmi, Maria Gazouli, Eleni Zografos & Mohadeseh Nemati
doi : 10.1007/s13346-021-00999-2
Breast cancer is a complex disease with multiple risk factors involved in its pathogenesis. Among these factors, microRNAs are considered for playing a fundamental role in the development and progression of malignant breast tumors. In recent years, various studies have demonstrated that several microRNAs exhibit increased or decreased expression in metastatic breast cancer, acting as indicators of metastatic potential in body fluids and tissue samples. The identification of these microRNA expression patterns could prove instrumental for the development of novel therapeutic molecules that either mimic or inhibit microRNA action. Additionally, an efficient delivery system mediated by viral vectors, nonviral carriers, or scaffold biomaterials is a prerequisite for implementing microRNA-based therapies; therefore, this review attempts to highlight essential microRNA molecules involved in the metastatic process of breast cancer and discuss recent advances in microRNA-based therapeutic approaches with potential future applications to the treatment sequence of breast cancer.
Exosomes as cell-derivative carriers in the diagnosis and treatment of central nervous system diseases
Gayatri Gopal Shetgaonkar, Shirleen Miriam Marques, Cleona E. M. DCruz, R. J. A. Vibhavari, Lalit Kumar & Rupesh Kalidas Shirodkar
doi : 10.1007/s13346-021-01026-0
Exosomes are extracellular vesicles with the diameter ranging from 50 to 100 nm and are found in different body fluids such as blood, cerebrospinal fluid (CSF), urine and saliva. Like in case of various diseases, based on the parent cells, the content of exosomes (protein, mRNA, miRNA, DNA, lipids and metabolites) varies and thus can be utilized as potential biomarker for diagnosis and prognosis of the brain diseases. Furthermore, utilizing the natural potential exosomes to cross the blood–brain barrier and by specifically decorating it with the ligand as per the desired brain sites therapeutics can be delivered to brain parenchyma. This review article conveys the importance of exosomes and their use in the treatment and diagnosis of brain/central nervous system diseases.
Construction of mannose-modified polyethyleneimine-block-polycaprolactone cationic polymer micelles and its application in acute lung injury
Meiling Su, Heping Hu, Xuan Zhao, Chengyuan Huang, Bowen Yang & Zongning Yin
doi : 10.1007/s13346-021-00976-9
This study evaluated the D-mannose modified polyethyleneimine-block-polycaprolactone biomacromolecule copolymer micelles (PCL-PEI-mannose) as a targeted delivery of the glucocorticoid dexamethasone (DXM) to lung inflammation tissues and enhances the vehicle for its anti-inflammatory effects. Dexamethasone was encapsulated in the hydrophobic core of cationic polymer micelles by solvent evaporation. The polymeric micelles exhibited sustained-release within 48Â h, good blood compatibility, and colloidal stability in vitro. The cellular uptake of mannose-modified micelles was higher compared with the non-modified micelles. And drug-loaded targeted micelles could inhibit the production of inflammatory factors in activated RAW264.7 cells. The distribution results indicated that drug-loaded targeted micelles highly improved the lung targeting ability, reduced the wet/dry ratio of injured lung tissue, and relieved the lung inflammation, accompanied by the decrease of inflammatory cell infiltration, myeloperoxidase activity, and inflammatory mediator levels in bronchoalveolar lavage fluid. These findings suggested that PCL-PEI-mannose delivery system could facilitate the lung-specific delivery and inhibit the inflammatory response. Collectively, PCL-PEI-mannose polymer micelles could be used as a potential delivery system for the treatment of acute lung injury (ALI).
γ-Cyclodextrin metal–organic framework as a carrier to deliver triptolide for the treatment of hepatocellular carcinoma
Zhe Li, Gang Yang, Rong Wang, Yuanyuan Wang, Jing Wang, Meng Yang, Chunai Gong & Yongfang Yuan
doi : 10.1007/s13346-021-00978-7
Triptolide (TPL) has been employed to treat hepatocellular carcinoma (HCC). However, the poor water solubility of TPL restricts its applications. Therefore, we prepared TPL-loaded cyclodextrin-based metal–organic framework (TPL@CD-MOF) to improve the solubility and bioavailability of TPL, thus enhancing the anti-tumor effect on HCC. The BET surface and the pore size of TPL@CD-MOF were 10.4 m2·g−1 and 1.1 nm, respectively. The results of XRD indicated that TPL in TPL@CD-MOF was encapsuled. TPL@CD-MOF showed a slower release than free TPL in vitro. Moreover, the CD-MOF improved the bioavailability of TPL. TPL@CD-MOF showed slightly higher, but statistically significant, anti-tumor efficacy in vitro and in vivo compared to free TPL. In addition, TPL@CD-MOF exhibited a modest improvement of the anti-tumor effects, which may be associated to the enhanced in vivo absorption. Overall, these findings suggested the potential CD-MOF as oral drug delivery carriers for anti-tumor drugs.
Conventional versus drug-eluting embolic transarterial chemoembolization with doxorubicin: comparative drug delivery, pharmacokinetics, and treatment response in a rabbit VX2 tumor model
Ron C. Gaba, Ramzy C. Khabbaz, Ruth N. Muchiri, Joseph D. Morrison, Lobna Elkhadragy, William M. Totura, Jonathan P. Samuelson, Herbert E. Whiteley, R
doi : 10.1007/s13346-021-00985-8
The purpose of this study was to compare intra-tumoral drug delivery, pharmacokinetics, and treatment response after doxorubicin (DOX) conventional (c-) versus drug-eluting embolic (DEE-) transarterial chemoembolization (TACE) in a rabbit VX2 liver tumor model. Twenty-four rabbits with solitary liver tumors underwent c-TACE (n = 12) (1:2 water-in-oil emulsion, 0.6 mL volume, 2 mg DOX) or DEE-TACE (n = 12) (130,000 70–150 µm 2 mg DOX-loaded microspheres). Systemic, intra-tumoral, and liver DOX levels were measured using mass spectrometry up to 7-day post-procedure. Intra-tumoral DOX distribution was quantified using fluorescence imaging. Percent tumor necrosis was quantified by a pathologist blinded to treatment group. Lobar TACE was successfully performed in all cases. Peak concentration (CMAX, µg/mL) for plasma, tumor tissue, and liver were 0.666, 4.232, and 0.270 for c-TACE versus 0.103, 8.988, and 0.610 for DEE-TACE. Area under the concentration versus time curve (AUC, µg/mL ∗ min) for plasma, tumor tissue, and liver were 18.3, 27,078.8, and 1339.1 for c-TACE versus 16.4, 26,204.8, and 1969.6 for DEE-TACE. A single dose of intra-tumoral DOX maintained cytotoxic levels through 7-day post-procedure for both TACE varieties, with a half-life of 1.8 (c-TACE) and 0.8 (DEE-TACE) days. Tumor-to-normal liver DOX ratio was high (c-TACE, 20.2; DEE-TACE, 13.3). c-TACE achieved significantly higher DOX coverage of tumor vs. DEE-TACE (10.8% vs. 2.3%; P = 0.003). Percent tumor necrosis was similar (39% vs. 37%; P = 0.806). In conclusion, in a rabbit VX2 liver tumor model, both c-TACE and DEE-TACE achieved tumoricidal intra-tumoral DOX levels and high tumor-to-normal liver drug ratios, though c-TACE resulted in significantly greater tumor coverage.
Dermatokinetic assessment of luliconazole-loaded nanostructured lipid carriers (NLCs) for topical delivery: QbD-driven design, optimization, and in vitro and ex vivo evaluations
Arisha Mahmood, Vamshi Krishna Rapalli, Srividya Gorantla, Tejashree Waghule & Gautam Singhvi
doi : 10.1007/s13346-021-00986-7
The present study is concerned with the QbD-based design and development of luliconazole-loaded nanostructured lipid carriers (NLCs) hydrogel for enhanced skin retention and permeation. The NLCs formulation was optimized employing a 3-factor, 3-level Box-Behnken design. The effect of formulation variable lipid content, surfactant concentration, and sonication time was studied on particle size and % EE. The optimized formulation exhibited particle size of 86.480 ± 0.799 nm; 0.213 ± 0.004 PDI, ≥ − 10 mV zeta potential and 85.770 ± 0.503% EE. The in vitro release studies revealed sustained release of NLCs up to 42 h. The designed formulation showed desirable occlusivity, spreadability (0.748 ± 0.160), extrudability (3.130 ± 1.570), and the assay was found to be 99.520 ± 0.890%. The dermatokinetics assessment revealed the Cmax Skin to be ~ 2-fold higher and AUC0–24 to be ~ 3-fold higher in the epidermis and dermis of NLCs loaded gel in contrast with the marketed cream. The Tmax of both the formulations was found to be 6 h in the epidermis and dermis. The obtained results suggested that luliconazole NLCs can serve as a promising formulation to enhance luliconazole’s antifungal activity and also in increasing patient compliance by reducing the frequency of application.
Raloxifene-loaded SLNs with enhanced biopharmaceutical potential: QbD-steered development, in vitro evaluation, in vivo pharmacokinetics, and IVIVC
Atul Jain, Teenu Sharma, Rajendra Kumar, O. P. Katare & Bhupinder Singh
doi : 10.1007/s13346-021-00990-x
Raloxifene hydrochloride, a second-generation selective estrogen receptor modulator, has been approved for the management of breast cancer. However, it is known to exhibit poor (~ 2%) and inconsistent oral bioavailability in humans, primarily ascribable to its low aqueous solubility, extensive first-pass metabolism, P-gp efflux, and presystemic glucuronide conjugation. The present research work entails the systematic development and evaluation of SLNs of RLX for its enhanced biopharmaceutical performance against breast cancer. Factor screening studies were conducted using Taguchi design, followed by optimization studies employing Box-Behnken design. Preparation of SLNs was carried out using glyceryl monostearate and Compritol® 888 ATO (i.e., lipid), Phospholipid S-100 (i.e., co-surfactant), and TPGS-1000 (i.e., surfactant) employing solvent diffusion method. The optimized formulation was evaluated for zeta potential, average particle size, field emission scanning electron microscope, transmission electron microscopy, and in vitro release study. Further, MCF-7 cells (cell cytotoxicity assay, apoptosis assay, and reactive oxygen species assay) and Caco-2 cells (cell uptake studies and P-gp efflux assay) were employed to evaluate the in vitro anticancer potential of the developed optimized formulation. In vivo pharmacokinetic studies were conducted in Sprague–Dawley rats to evaluate the therapeutic profile of the developed formulation. The optimized SLN formulations exhibited a mean particle size of 109.7 nm, PDI 0.289 with a zeta potential of − 13.7 mV. In vitro drug dissolution studies showed Fickian release, with release exponent of 0.137. Cell cytotoxicity assay, apoptosis assay, and cellular uptake indicated 6.40-, 5.40-, and 3.18-fold improvement in the efficacy of RLX-SLNs vis-à -vis pure RLX. Besides, the pharmacokinetic studies indicated quite significantly improved biopharmaceutical performance of RLX-SLNs vis-à -vis pure drug, with 4.06-fold improvement in Cmax, 4.40-fold in AUC(0-72 h), 4.56-fold in AUC(0-∞), 1.53-fold in Ka, 2.12-fold in t1/2, and 1.22-fold in Tmax. Further, for RLX-SLNs and pure drug, high degree of level A linear correlation was established between fractions of drug dissolved (in vitro) and of drug absorbed (in vivo) at the corresponding time-points. Stability studies indicated the robustness of RLX-SLNs when stored at for 3 months. Results obtained from the different studies construe promising the anticancer potential of the developed RLX-SLNs, thereby ratifying the lipidic nanocarriers as an efficient drug delivery strategy for improving the biopharmaceutical attributes of RLX.
Liver targeting of ledipasvir via galactosylated chitosan–coated spanlastics: chemical synthesis, statistical optimization, in vitro, and pharmacokinetic evaluation
Ahmed M. Fatouh, Ahmed H. Elshafeey & Ahmed Abdelbary
doi : 10.1007/s13346-021-00993-8
Ledipasvir is an effective direct acting antiviral agent used in the treatment of hepatitis C virus. The high price of ledipasvir was a reason for its limited provision to wide population of HCV patients.
Release of vascular agonists from liposome-microbubble conjugate by ultrasound-mediated microbubble destruction: effect on vascular function
Carlos A. Franco-Urquijo, J. ?ngel Navarro-Becerra, Amelia R?os & Bruno Escalante
doi : 10.1007/s13346-021-00994-7
The endothelium is a single cell layer of the vessel wall and a key regulator of blood flow in vascular beds. Local and systemic pathologies have been associated with alterations in endothelial function. However, targeting the endothelium with vasoconstrictor or vasodilator drugs is often accompanied by systemic effects. Here, we evaluated a liposome-microbubble delivery system as a vascular hydrophilic agonist carrier. Phenylephrine (Phe) or acetylcholine (Ach)-loaded liposomes were conjugated to microbubbles. The drug release was triggered by ultrasound (US), and the vascular response was assessed in rat aortic rings using an isolated organ chamber.
Controlled release of pharmaceutical agents using eutectic modified gelatin
Wanwan Qu, Idrees B. Qader & Andrew P. Abbott
doi : 10.1007/s13346-021-00998-3
Deep eutectic solvent (DES) is a class of ionic liquids, consisting of a mixture generally formed by combining hydrogen bond donors (HBDs) such as alcohols, amides and carboxylic acids with various quaternary ammonium salts. The decrease in melting points of the constituents is due to the charge delocalization during formation of hydrogen bonding between the hydrogen bond acceptor with the hydrogen bond donor. This can be considered one of the main reasons for increasing solubility and absorption of DESs. Most active pharmaceutical ingredients (APIs) have polar functional groups containing amide, carboxylic acid, alcohol or quaternary ammonium groups. These tend to increase the melting point of the compounds, but they can be used to form eutectic mixtures.
Preparation and characterization of 3D printed PLA microneedle arrays for prolonged transdermal drug delivery of estradiol valerate
Afsoun Khosraviboroujeni, Seyedeh Zahra Mirdamadian, Mohsen Minaiyan & Azade Taheri
doi : 10.1007/s13346-021-01006-4
Biodegradable polymeric microneedle arrays (BPMNAs) could be explored as potential devices for transdermal drug delivery, which can provide a painless and safe drug delivery method. BPMNAs could also provide high drug-loading capacity and prolonged drug delivery once integrated with a drug reservoir. However, the fabrication of MNAs with a drug reservoir is expensive and requires complicated procedures. The present study was conducted to describe the preparation of a reservoir-based BPMNA containing estradiol valerate using polylactic acid (PLA) with the combination of FDM 3D printing and injection volume filling techniques. The tip size of the 3D printed needles decreased to 173 μm utilizing a chemical etching process. The content of estradiol valerate loaded in the 3D printed PLA MNAs was 29.79 ± 0.03 mg, and the release was in a prolonged manner for up to 7 days.
Direct comparison of two kinds of linoleic acid-docetaxel derivatives: in vitro cytotoxicity and in vivo antitumor activity
Lirui Jia, Ying Liu, Meng Li, Yongjun Wang & Zhonggui He
doi : 10.1007/s13346-021-01010-8
Rational designed lipid-drug derivatives provide a favorable approach to improve the druggability of highly hydrophobic prototypes. It has been regarded as common sense that good cytotoxicity is the guarantee of superior anticancer efficacy for candidate derivatives screening. However, does it apply to lipid-drug conjugate-based self-assembled nanoparticles? Here, we established the above two derivatives and a non-correlation between the cytotoxic activity in vitro and drug efficacy in vivo was found. The IC50 of DSL NPs (DTX-S-LA nanoparticles) and DL NPs (DTX-LA nanoparticles) were 4.02 and 209.6Â ng/mL (DTX equivalent concentration), respectively. However, DL NPs unexpectedly showed stronger tumor inhibition abilities than DSL NPs.
Exploitation of nanocrystal suspension as an effective oral formulation for oxfendazole
Yuzhu Sun, Dongmei Chen, Ying Zhao, Kaixiang Zhou, Bao Zhang, Haiting Wang & Shuyu Xie
doi : 10.1007/s13346-021-01012-6
An oxfendazole (OFZ) nanocrystal suspension was prepared by acid–base neutralization and crystallization combined with ultrasonic dispersion to overcome the challenge of its poor oral bioavailability. The nanosuspensions were screened and optimized by single-factor experiments and an orthogonal design using size and appearance as indices. The morphology (differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD)) properties and pharmacokinetics of the best formulation were further developed. The results showed that the best cosolvent and stabilizer were malic acid and hydrogenated castor oil polyoxyethylene ether (HEL-40), respectively. Scanning electron microscopy demonstrated that the oxfendazole nanocrystals are irregular sheets with relative uniformity.
Quality by design (QbD)–based fabrication of atazanavir-loaded nanostructured lipid carriers for lymph targeting: bioavailability enhancement using chylomicron flow block model and toxicity studies
Vishal C. Gurumukhi & Sanjaykumar B. Bari
doi : 10.1007/s13346-021-01014-4
Atazanavir (ATV) is widely used as anti-HIV agent having poor aqueous solubility needs to modulate novel drug delivery system to enhance therapeutic efficiency and safety. The main objective of the present work was to fabricate ATV-loaded nanostructured lipid carriers (NLCs) employing quality by design (QbD) approach to address the challenges of bioavailability and their safety after oral administration. Herein, the main objective was to identify the influencing variables for the production of quality products. Considering this objective, quality target product profile (QTPP) was assigned and a systematic risk assessment study was performed to identify the critical material attributes (CMAs) and critical process parameter (CPP) having an influence on critical quality attributes (CQAs).
Tailoring drug co-delivery nanosystem for mitigating U-87 stem cells drug resistance
Amir Barzegar Behrooz, Reza Vazifehmand, Asilah Ahmad Tajudin, Mas Jaffri Masarudin, Zamberi Sekawi, Malihe Masomian & Amir Syahir
doi : 10.1007/s13346-021-01017-1
Glioblastoma multiforme (GBM) is the most prevalent form of brain tumor, which generally has a poor prognosis. According to consensus, recurrence of the tumor and chemotherapy resistance acquisition are the two distinguishing features of GBM originated from glioblastoma stem cells (GSCs). To eliminate these obstacles inherent in GBM chemotherapy, targeting GSCs through a smart drug delivery system has come to the front position of GBM therapeutics. In this study, B19 aptamer (Apt)-conjugated polyamidoamine (PAMAM) G4C12 dendrimer nanoparticles (NPs), called Apt-NPs, were formulated for the co-delivery of paclitaxel (PTX) and temozolomide (TMZ) to U-87 stem cells. These drugs were loaded using a double emulsification solvent evaporation method. As a result, drug-loaded Apt-NPs significantly inhibited the tumor growth of U-87 stem cells, by the initiation of apoptosis via the downregulation of autophagic and multidrug resistance (MDR) genes.
Improving dexamethasone drug loading and efficacy in treating arthritis through a lipophilic prodrug entrapped into PLGA-PEG nanoparticles
Rosana Sim?n-V?zquez, Nicolas Tsapis, Mathilde Lorscheider, Ainhoa Rodr?guez, Patricia Calleja, Ludivine Mousnier, Encarnaci?n de Miguel Villegas, ?fr
doi : 10.1007/s13346-021-01112-3
Targeted delivery of dexamethasone to inflamed tissues using nanoparticles is much-needed to improve its efficacy while reducing side effects. To drastically improve dexamethasone loading and prevent burst release once injected intravenously, a lipophilic prodrug dexamethasone palmitate (DXP) was encapsulated into poly(DL-lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) nanoparticles (NPs). DXP-loaded PLGA-PEG NPs (DXP-NPs) of about 150Â nm with a drug loading as high as 7.5% exhibited low hemolytic profile and cytotoxicity. DXP-NPs were able to inhibit the LPS-induced release of inflammatory cytokines in macrophages. After an intravenous injection to mice, dexamethasone (DXM) pharmacokinetic profile was also significantly improved. The concentration of DXM in the plasma of healthy mice remained high up to 18Â h, much longer than the commercial soluble drug dexamethasone phosphate (DSP).
Molecular hybridization combining tumor homing and penetrating peptide domains for cellular targeting
Ruchika Goyal, Gaurav Jerath, Aneesh Chandrasekharan, Yvonne Christian, T. R. Santhosh Kumar & Vibin Ramakrishnan
doi : 10.1007/s13346-021-01035-z
A complete peptide-based drug delivery unit has been designed with a tumor homing domain chemically linked to a syndiotactic cell-penetrating domain. The designed peptides were synthesized, characterized, and tested in vitro for cellular uptake and cytotoxicity evaluation. The differential uptake, cellular internalization, negligible hemotoxicity, selective toxicity to MDA-MB-231 breast cancer cells, and the superior penetration in three-dimensional MDA-MB-231 tumorospheres confirm their utility as a promising delivery vector.
