Lipid-polymer Nanoparticles Research Articles

Hybrid Lipid Polymer Nanoparticles for Combined Chemo- and Photodynamic Therapy.

Retinoblastoma is a malignant tumor of the retina in infants. Conventional therapies are associated to severe side effects and some of them induce secondary tumors. Photodynamic therapy (PDT) thus appears as a promising alternative as it is nonmutagenic and generates minimal side effects. The effectiveness of PDT requires the accumulation of a photosensitizer (PS) in the tumor. However, most porphyrins are hydrophobic and aggregate in aqueous medium. Their incorporation into a nanocarrier may improve their delivery to the cell cytoplasm. In this work, we designed biodegradable liponanoparticles (LNPs) consisting of a poly(d,l)-lactide (PDLLA) nanoparticle coated with a phospholipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine/1,2-dioleoyl-3-trimethylammonium-propane) bilayer. An anticancer drug, beta-lapachone (β-Lap) and a PS, m-THPC, were co-encapsulated for combined chemo- and PDT because it has been suggested that they may have a synergistic effect based on the activation of β-Lap by PDT-induced over-expression of the enzyme NQO1. Using dynamic light scattering measurements, cryogenic transmission electron microscopy, and fluorescence confocal microscopy, we selected the appropriate conditions for the encapsulation of the compounds. LNPs were internalized in retinoblastoma cells within few hours. No obvious synergistic effect related to the activation of β-Lap by PDT was observed. Conversely, the LNPs were cytotoxic at lower doses of the two encapsulated compounds as compared to the single therapies. Analysis of the combinatorial treatment showed that PDT and chemotherapy had an additive effect on the viability of retinoblastoma cells.

Core-shell lipid-polymer nanoparticles as a promising ocular drug delivery system to treat glaucoma

Nowadays, tremendous researches have been focused on the core-shell lipid-polymer nanoparticles (LPNs) due to the advantages of both liposomes and polymer nanoparticles. In this work, LPNs were applied to encapsulate brinzolamide (Brz-LPNs) for achieving sustained drug release, improving drug corneal permeation and enhancing drug topical therapeutic effect. The structure of Brz-LPNs was composed of poly(lactic-co-glycolic) acid (PLGA) nanocore which encapsulated Brz (Brz-NPs) and lipid shell around the core. Brz-LPNs were prepared by a modified thin-film dispersion method. With the parameters optimization of Brz-LPNs, optimal Brz-LPNs showed an average particle size of 151.23 ± 1.64 nm with a high encapsulation efficiency (EE) of 86.7% ± 2.28%. The core-shell structure of Brz-LPNs were confirmed by transmission electronic microscopy (TEM). Fourier transformed infrared spectra (FTIR) analysis proved that Brz was successfully entrapped into Brz-LPNs. Brz-LPNs exhibited obvious sustained release of Brz, compared with AZOPT® and Brz-LPs. Furthermore, the corneal accumulative permeability of Brz-LPNs significantly increased compared to the commercial available formulation (AZOPT®) in vitro. Moreover, Brz-LPNs (1 mg/mL Brz) showed a more sustained and effective intraocular pressure (IOP) reduction than Brz-LPs (1 mg/mL) and AZOPT® (10 mg/mL Brz) in vivo. In conclusion, Brz-LPNs, as promising ocular drug delivery systems, are well worth developing in the future for glaucoma treatment.

A Comprehensive Physicochemical, In Vitro and Molecular Characterization of Letrozole Incorporated Chitosan-Lipid Nanocomplex

The aim of this study is to show a new mesomicroscopic insight into Letrozole (LTZ) loaded nanocomplexes and their ex vivo characteristics as a drug delivery system. The LTZ loaded hybrid chitosan-based carrier was fabricated using a modified ionic crosslinking technique and characterized in more detail. To understand the mechanism of LTZ action encapsulated in the hybrid polymer-lipid carrier, all-atom molecular dynamics simulations were also used. The physicochemical properties of the carrier demonstrated the uniform morphology, but different drug loading ratios. In vitro cytotoxic activity of the optimized carrier demonstrated IC50 of 67.85 ± 0.55nM against breast cancer cell line. The ex vivo study showed the positive effect of nanocomplex on LTZ permeability 7-10 fold greater than the free drug. The molecular dynamic study also confirmed the prsence of hydrophobic peak of lipids at a distance of 5Å from the center of mass of LTZ which proved drug entrapment in the core of nanocomplex. The hybrid nanoparticle increased the cytotoxicity and tissue permeability of LTZ for oral delivery. This study also confirmed the atomic mesostructures and interaction of LTZ in the core of hybrid polymer-lipid nanoparticles.

Mucus penetration enhanced lipid polymer nanoparticles improve the eradication rate of Helicobacter pylori biofilm

The resistance of Helicobacter pylori (H. pylori) to conventional antibiotic treatments becomes prevalent recently. The biofilm formation was found to be highly correlated with the antibiotic resistance of H. pylori in the last decades. Moreover, H. pylori colonizes on the digestive tract epithelium located under the mucus layers, which further reduces therapeutic efficacy as mucus layers trap and remove exogenous substances including drugs. Herein, we reported a novel lipid polymer nanoparticles (LPNs) to overcome both biofilm and mucus layers obstruction. LPNs employed chitosan nanoparticle (CS NPs) as the core, mixed lipid layer containing rhamnolipids (RHL) as the shell and the surface of LPNs was further modified with DSPE-PEG2000 to improve hydrophilicity. Clarithromycin (CLR), a first-line drug for H. pylori infection, was encapsulated in LPNs. LPNs, especially the formulation utilizing 100% of RHL as the lipid shell, exhibited excellent eradicating ability to H. pylori biofilm, which was mainly reflected in the significant reduction of biofilm biomass and viability, destruction of biofilm architecture and elimination of extracellular polymeric substances (EPS). The anti-biofilm activities of LPNs are related to: 1) the disrupting effect of RHL on biofilm matrix; 2) antibacterial effects of CLR and CS NPs on biofilm bacteria and 3) inhibitory effects of CS NPs and RHL on bacteria adhesion and biofilm formation. Furthermore, PEGylated LPNs could rapidly penetrate through mucus without interacting with mucins and effectively eradicate H. pylori biofilm under mucus layer. In conclusion, a novel approach of drug-containing LPNs that could penetrate through mucus layers and effectively eradicate H. pylori biofilm provides new ways to treat persistent H. pylori infections.

Lipid-polymer nanoparticles with CD133 aptamers for targeted delivery of all-trans retinoic acid to osteosarcoma initiating cells

Osteosarcoma, a common type of bone cancer in children, and represents an aggressive and fetal cancer worldwide. Osteosarcoma initiating cells are considered to be a subpopulation of cancer cells which contribute to the progression, recurrence, metastasis and multi-drug resistance of osteosarcoma. CD133 is considered to be one marker for osteosarcoma initiating cells. All-trans retinoic acid (ATRA), an active metabolite of vitamin A under the family retinoid, is an up-and-coming drug which was able to effectively treat various cancer initiating cells. Nevertheless, there have been no research that reported the activity of ATRA against osteosarcoma initiating cells. In this research, we hereby examined the potential activity of ATRA in osteosarcoma initiating cells, and developed lipid-polymer nanoparticles with CD133 aptamers for targeted ATRA delivery to osteosarcoma initiating cells. Using the cytotoxicity assay, colony formation assay, tumorsphere formation assay and flow cytometry, the therapeutic effect of ATRA and ATRA-loaded lipid-polymer nanoparticles conjugated with CD133 aptamers (ATRA-PLNP-CD133) against osteosarcoma initiating cells were investigated. The results showed that ATRA exerted potent activity towards osteosarcoma initiating cells. ATRA-PLNP-CD133, which showed a size of 129.9 nm and a sustained release of ATRA during 144 h, was demonstrated to efficiently and specifically promote the ATRA delivery to osteosarcoma initiating cells, and achieve superior therapeutic efficacy in osteosarcoma compared with ATRA and non-targeted nanoparticles. This is the first report of the therapeutic efficacy of ATRA towards osteosarcoma initiating cells, and the increased ATRA delivery by nanoparticles to osteosarcoma initiating cells using CD133 aptamers. ATRA-PLNP-CD133 represent an up-and coming approach for the therapy of osteosarcoma initiating cells.

Rational design of polymer-lipid nanoparticles for docetaxel delivery.

In this work, a stable nanocarrier for the anti-cancer drug docetaxel was rational designed. The nanocarrier was developed based on the solid lipid nanoparticle preparation process aiming to minimize the total amount of excipients used in the final formulations. A particular interest was put on the effects of the polymers in the final composition. In this direction, two poloxoamers -Pluronic F127 and F68- were selected. Some poloxamers are well known to be inhibitors of the P-glycoprotein efflux pump. Additionally, their poly-ethylene-oxide blocks can help them to escape the immune system, making the poloxamers appealing to be present in a nanoparticle designed for the treatment of cancer. Within this context, a factorial experiment design was used to achieve the most suitable formulations, and also to identify the effects of each component on the final (optimized) systems. Two final formulations were chosen with sizes < 250 nm and PDI < 0.2. Then, using dynamic light scattering and nanotracking techniques, the stability of the formulations was assessed during six months. Structural studies were carried on trough different techniques: DSC, x-ray diffraction, FTIR-AR and Molecular Dynamics. The encapsulation efficiency of the anticancer drug docetaxel (> 90%) and its release dynamics from formulations were measured, showing that the polymer-lipid nanoparticle is suitable as a drug delivery system for the treatment of cancer.

Nanocarriers for drug delivery applications

Nanobiotechnology research has recently provided numerous basic and applied advances in the health sector. Nanocarriers have been developed for efficient drug delivery and diagnostic tools. Nanocarrier enables an effective, targeted biomolecular interaction in order to lower side effects caused during the treatment. Here, we review the problems associated with the conventional drug development and its delivery system. The efficacy of the treatment can be improved by the usage of efficient nanocarriers such as polymeric nanocarriers, superparamagnetic nanoparticles, quantum dot, dendrimers and lipid nanoparticles. We discuss the mechanisms of delivery. This review may aid in providing better solutions for unsolved problems that prevails with the day-to-day in silico, in vitro and in vivo drug delivery model development.

Synthesis and Characterization of Placental Chondroitin Sulfate A (plCSA)-Targeting Lipid-Polymer Nanoparticles.

An effective cancer therapeutic method reduces and eliminates tumors with minimal systemic toxicity. Actively targeting nanoparticles offer a promising approach to cancer therapy. The glycosaminoglycan placental chondroitin sulfate A (plCSA) is expressed on a wide range of cancer cells and placental trophoblasts, and malarial protein VAR2CSA can specifically bind to plCSA. A reported placental chondroitin sulfate A binding peptide (plCSA-BP), derived from malarial protein VAR2CSA, can also specifically bind to plCSA on cancer cells and placental trophoblasts. Hence, plCSA-BP-conjugated nanoparticles could be used as a tool for targeted drug delivery to human cancers and placental trophoblasts. In this protocol, we describe a method to synthesize plCSA-BP-conjugated lipid-polymer nanoparticles loaded with doxorubicin (plCSA-DNPs); the method consists of a single sonication step and bioconjugate techniques. In addition, several methods for characterizing plCSA-DNPs, including determining their physicochemical properties and cellular uptake by placental choriocarcinoma (JEG3) cells, are described.

Optimization of a Degradable Polymer-Lipid Nanoparticle for Potent Systemic Delivery of mRNA to the Lung Endothelium and Immune Cells.

mRNA therapeutics hold great potential for treating a variety of diseases through protein-replacement, immunomodulation, and gene editing. However, much like siRNA therapy the majority of progress in mRNA delivery has been confined to the liver. Previously, we demonstrated that poly(β-amino esters), a class of degradable polymers, are capable of systemic mRNA delivery to the lungs in mice when formulated into nanoparticles with poly(ethylene glycol)-lipid conjugates. Using experimental design, a statistical approach to optimization that reduces experimental burden, we demonstrate herein that these degradable polymer-lipid nanoparticles can be optimized in terms of polymer synthesis and nanoparticle formulation to achieve a multiple order-of-magnitude increase in potency. Furthermore, using genetically engineered Cre reporter mice, we demonstrate that mRNA is functionally delivered to both the lung endothelium and pulmonary immune cells, expanding the potential utility of these nanoparticles.

Core–shell‐type polymer–lipid nanoparticles for the transdermal delivery of daidzein

Daidzein (DZ) is an ideal Chinese herb for treating cardiocerebrovascular disease. Despite its poor water solubility and limited application, DZ was successfully loaded, along with penetration enhancer azone, onto core–shell-type polymer–lipid nanoparticles through a two-step preparation method. The mean particle diameter, encapsulation efficiency, and drug-loading rate of DZ–polymer-azone–lipid nanoparticles (D-P-Azone-LNs) were 77.59 ± 2.26 nm, 79.91% ± 1.46%, and 1.50% ± 0.02%, respectively. In skin penetration experiment, the cumulative amount of DZ from D-P-Azone-LN reached 14.91 μg·cm−2 at 72 h. This amount was 1.44 and 6.01 times higher than those of DZ–polymer–lipid nanoparticles (D-P-LNs) and DZ solution, respectively. Confocal laser scanning microscopy was used to conduct a qualitative analysis. In vivo study, D-P-Azone-LN achieved better skin retention than those of D-P-LN and DZ. Furthermore, no significant irritation was observed in the skin irritation experiment. These results suggested that the core–shell polymer–lipid nanoparticles, which combined the properties of polymer and lipid nanoparticles, can offer a useful formulation for enhancing the skin permeation of drug for transdermal delivery.

Sustained Release of Nanoformulation of Diethyl Carbamazine (Dec) for Filariasis – a Review

Lymphatic filariasis (LF), is a mosquito vector-borne disease and a major public health problem in the tropical countries. The annual mass drug administration (MDA) in India was studied in 1996-97. It was introduced with single dose of Diethylcarbamazine and was investigated as a pilot project covering 41millon population. The study was extended to 77million population by 2002. The MDA is one of the strategies to eliminate LF in India. Liposomes, polymeric and solid lipid nanoparticles are the most promising nanopharmaceuticals which are easy to formulate, cheaper and can bring prolific consequences for filariasis management.

Design and biological activity of novel stealth polymeric lipid nanoparticles for enhanced delivery of hydrophobic photodynamic therapy drugs

Advances in in vivo stability and preferential tumor uptake of cancer nanomedicine are warranted for effective chemotherapy. Here, we describe a novel nanoformulation using an unconventional polymeric tubule-forming phospholipid, DC8,9PC. We report that DC8,9PC transitions to stable vesicles (LNPs) in the presence of PEGylated lipid (DSPE-PEG2000); the resulting DC8,9PC:DSPE-PEG2000 LNPs efficiently included a hydrophobic PDT drug, HPPH. Remarkably, these LNPs incorporated unusually high DSPE-PEG2000 concentrations; LNP10-HPPH and LNP20-HPPH (10 & 20 mol% PEGylated lipid, respectively) exhibited >90% serum stability at 37 °C. Increased PEGylation in the LNPs correlated with enhanced tumor accumulation in intravenously injected HT29 tumor mouse xenographs. Colon-26 bearing BALB/c mice, intravenously injected with LNP20-HPPH showed superior PDT efficacy and animal survival (no tumor recurrence up to 100 days) as compared to a formulation currently used in clinical trials. Taken together, we present a simple stealth binary lipid nanosystem with enhanced efficiency of tumor accumulation and superior therapeutic efficacy.

Effect of Binary Organic Solvents Together with Emulsifier on Particle Size and In vitro Behavior of Paclitaxel-Encapsulated Polymeric Lipid Nanoparticles.

Biodegradable nanoparticles with diameters between 100 nm and 500 nm are of great interest in the contexts of targeted delivery. The present work provides a review concerning the effect of binary organic solvents together with emulsifier on particle size as well as the influence of particle size on the in vitro drug release and uptake behavior. The polymeric lipid nanoparticles (PLNs) with different particle sizes were prepared by using binary solvent dispersion method. Various formulation parameters such as binary organic solvent composition and emulsifier types were evaluated on the basis of their effects on particle size and size distribution. PLNs had a strong dependency on the surface tension, intrinsic viscosity and volatilization rate of binary organic solvents and the hydrophilicity/hydrophobicity of emulsifiers. Acetone-methanol system together with pluronic F68 as emulsifier was proved to obtain the smallest particle size. Then the PLNs with different particle sizes were used to investigate how particle size at nanoscale affects interacted with tumor cells. As particle size got smaller, cellular uptake increased in tumor cells and PLNs with particle size of ~120 nm had the highest cellular uptake and fastest release rate. The paclitaxel (PTX)-loaded PLNs showed a size-dependent inhibition of tumor cell growth, which was commonly influenced by cellular uptake and PTX release. The PLNs would provide a useful means to further elucidate roles of particle size on delivery system of hydrophobic drugs.

RGD peptide-modified, paclitaxel prodrug-based, dual-drugs loaded, and redox-sensitive lipid-polymer nanoparticles for the enhanced lung cancer therapy

One approach to improve the targeted therapeutic efficiency of lung cancer is to deliver drugs using nano-scaled systems. In this study, RGD peptide-modified, paclitaxel (PTX) prodrug-based, dual-drugs loaded, and redox-sensitive lipid-polymer nanoparticles were developed and the in vitro and in vivo antitumor efficiency was evaluated in lung cancer cells and tumor bearing animal models. RGD-modified PTX and cisplatin (CDDP) loaded LPNs (RGD-ss-PTX/CDDP LPNs) have sizes around 190 nm, and zeta potentials of −35 mV. The half-maximal inhibitory concentration (IC50) values were 26.7 and 75.3 μg/mL for drugs loaded LPNs and free drugs combination, which indicates significantly higher antitumor activity of LPNs than free drugs. RGD-ss-PTX/CDDP LPNs also exhibited the best antitumor efficiency in vivo, which inhibited the tumor size of mice from 1486 mm3 to 263 mm3. The results illustrated that the system could successfully load drugs and achieve synergistic combination lung cancer treatment efficiency with lower systemic toxicity compared with free drugs counterparts. The resulting system could be facilitated as a promising targeted nanomedicine for the treatment of lung cancer.

Targeted salinomycin delivery with EGFR and CD133 aptamers based dual-ligand lipid-polymer nanoparticles to both osteosarcoma cells and cancer stem cells

We previously developed salinomycin (sali)-entrapped nanoparticles labeled with CD133 aptamers which could efficiently eliminate CD133+ osteosarcoma cancer stem cells (CSCs). However, sufficient evidences suggest that the simultaneous targeting both CSCs and cancer cells is pivotal in achieving preferable cancer therapeutic efficacy, due to the spontaneous conversion between cancer cells and CSCs. We hereby constructed sali-entrapped lipid-polymer nanoparticles labeled with CD133 and EGFR aptamers (CESP) to target both osteosarcoma cells and CSCs. The cytotoxicity of CESP in osteosarcoma cells and CSCs was superior to that of single targeting or nontargeted sali-loaded nanoparticles. Administration of CESP in vivo showed the best efficacy in inhibiting tumor growth than other controls in osteosarcoma-bearing mice. Thus, CESP was demonstrated to be capable of efficiently targeting both osteosarcoma CSCs and cancer cells, and it represents an effective potential approach to treat osteosarcoma.

Visual validation of the measurement of entrapment efficiency of drug nanocarriers

Entrapment efficiency (EE) is a crucial parameter for the evaluation of nanocarriers. The accurate measurement of EE demands clear separation of nanocarriers from free drugs, which so far has not been clearly validated due to a lack of functional tools to identify nanocarriers. Herein, an environment-responsive water-quenching fluorophore was employed to label and identify model nanocarriers, polycaprolactone nanoparticles (PN), methoxy polyethylene glycol-poly(d,l-lactic acid) polymeric micelles (PM) and solid lipid nanoparticles (SLN). The separation process of three commonly used methods (centrifugation, ultrafiltration and gel permeation chromatography) was visualized by live imaging. The separation efficiency of the centrifugation method is very poor, especially for PM (40 nm), SLN (100 nm) and PN (100 nm); only PN (200 nm) can be efficiently separated but at a consumption of enormous energy. The ultrafiltration method shows the best separation efficiency with only 0.32–0.93% of leakage of the nanocarriers. Gel permeation chromatography exhibits good separation as well but suffers from low recovery, a potential factor that might compromise the accuracy of EE measurement. In conclusion, the ultrafiltration method is the method of choice for efficient separation and accurate measurement of EE.

Lipid-based nanoparticles as novel drug delivery systems for antimicrobial agents

Despite the development of novel drugs and technologies in combating the infectious diseases, they remain as a global health challenge. The use of conventional antimicrobial drugs are always associated with problems such as antimicrobial resistance, adverse effects, and inefficient drug delivery. In this regard, the unique physiochemical properties of the nanoparticles have led to increase in the researches on nanoparticles and their application as promising antimicrobial products. Lipid nanoparticles (LNPs) are new carrier systems developed as an alternative to traditional nanoparticle vehicles. The solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLCs), lipid-drug conjugates (LDCs), Lipid-core nanocapsules (LNCs) and lipid-polymer nanoparticles (LPNs) are carriers with a lipid matrix showing advantages for different applications due to the use of biodegradable, and biocompatible lipids. LNPs have exclusive properties owing to their ultra-small size and high surface area, thereby, they are able to increase drug targeting, treatment efficiency and reduce the toxicity of antimicrobial drugs. LNPs are often used as sustained release systems, and they also used for improving drug bioavailability. It has been found that the composition and structure of LNPs are two critical factors that may influence their pharmaceutical performance in different body organs. This review focuses on the development of LNP systems for antimicrobial drugs delivery and gives an overview on the modern LNP- based therapeutic strategies against the infections. The mechanism of action and advantages of these nanoparticles as antibacterial, antifungal, antiviral and anti-parasitic agents are highlighted in this review.

Enhanced rapamycin delivery to hemangiomas by lipid polymer nanoparticles coupled with anti-VEGFR antibody

The most common tumors in children are infantile hemangiomas which could cause morbidity and severe complications. The development of novel alternative drugs to treat infantile hemangiomas is necessary, since Hemangeol is the only US Food and Drug Administration-approved drug for infantile hemangiomas. However, Hemangeol has several disadvantages, including a high frequency of administration and adverse effects. Rapamycin is a well‑established antiangiogenic drug, and we have previously developed rapamycin lipid polymer nanoparticles (R‑PLNPs) as a local sustained‑release drug delivery system to achieve controlled rapamycin release and to decrease the frequency of administration and side effects of rapamycin. To improve the targeting of R‑PLNPs to infantile hemangiomas in the present study, R‑PLNPs were modified to include an antibody against vascular endothelial growth factor receptor (VEGF). The characteristics, and the anti‑hemangioma activity of the resulting R‑PLNPs coupled with the anti‑VEGFR2 antibody (named R‑PLNPs‑V) were examined invitro and invivo. R‑PLNPs‑V possessed a small size (115nm) and sustained drug release for 6days. The anti‑VEGFR2 antibody promoted the targeting and cytotoxic effect of R‑PLNPs‑V to human hemangioma endothelial cells and human umbilical vein endothelial cells. Using a subcutaneous infantile hemangioma xenograft in mice, the invivo therapeutic effect (evaluated with hemangioma weight, volume, and microvessel density) of R‑PLNPs‑V was demonstrated to be superior compared with rapamycin alone and other non‑targeted nanoparticles, without any total body weight loss. In summary, R‑PLNPs‑V could facilitate targeted delivery and sustained release of rapamycin to infantile hemangiomas, and thus may represent a promising candidate treatment for infantile hemangiomas.

Dual redox/pH-responsive hybrid polymer-lipid composites: Synthesis, preparation, characterization and application in drug delivery with enhanced therapeutic efficacy

The development of intelligent drug delivery system that can efficiently deliver drug to targeted site and release the cargo in a controlled manner is of great significance for cancer chemotherapy. In the present study, dual redox/pH-sensitive amphiphilic copolymer, cholesterol modified poly (β-amino esters)-grafted disulfide poly (ethylene glycol) methyl ether (PAE(-ss-mPEG)-g-Chol), is successfully synthesized via Michael-type step polymerization using disulfide linkage-containing PEG segment. PEGylated lipid is introduced to fabricate the doxorubicin (DOX)-loaded hybrid polymer-lipid nanoparticles (NPs) with (DOX-HDPLNPs) or without (DOX-HPLNPs) disulfides to receive stable NPs with enhanced loading capacity and improved cellular uptake ability as well as serum stability. The HDPLNPs show not only pH-sensitivity because of poly(β-amino esters) (PAE) residues in main chain but also the redox-responsivity due to the disulfides on the side chains with PEG segments. As expected, the DOX-HDPLNPs exhibited the extended blood circulation time and higher serum stability in normal physiological environment, but once deposited in the tumor microenvironment (e.g. low pH value and high GSH concentration), they underwent a dramatic size transition and charge reversal. These features not only can facilitate the NPs accumulation through the enhanced permeability and retention (EPR) effect and endocytosis by tumor cells but also realize the drug controlled release and more efficient tumor inhibition. The in vitro and in vivo results demonstrate that the DOX-HDPLNPs possess the highest therapeutic efficacy with high cellular uptake and negligible cytotoxicity compared to the controls and free drug. Therefore, the HDPLNPs have good potential as smart delivery platforms for hydrophobic anticancer drug delivery due to high uptake by tumor cells and redox/pH-triggered drug release.

Advancements in nanotechnology for drug delivery

Background: Nanoparticles (NPs) have emerged as a transformative technology in drug delivery, offering advancements in precision medicine, especially in managing chronic diseases and gastrointestinal (GIT) disorders. Due to their unique properties and the ability to be engineered at the nanoscale, NPs provide enhanced targeting, controlled release, and reduced side effects compared to traditional drug delivery systems. Aim: This review aims to summarize recent innovations in nanoparticle technology and their applications in drug delivery systems, with a focus on gastrointestinal diseases. Methods: The review synthesizes current literature on NP technologies and their applications in treating GIT disorders. It covers a range of nanocarriers, including metal and polymeric NPs, liposomes, hydrogels, and lipid nanoparticles. The review evaluates their effectiveness, challenges, and advancements in GIT drug delivery. Results: Recent advancements in NP technology have demonstrated significant potential in improving drug delivery to the GIT. Innovations include pH-sensitive NPs, enzyme-responsive NPs, and targeted formulations for diseases such as inflammatory bowel disease (IBD) and colorectal cancer. Lipid nanoparticles, including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), have shown promise in enhancing stability, targeting, and drug release profiles.