Potential Delivery Research Articles

Cationized extracellular vesicles for gene delivery

Last decade, extracellular vesicles (EVs) attracted a lot of attention as potent versatile drug delivery vehicles. We reported earlier the development of EV-based delivery systems for therapeutic proteins and small molecule chemotherapeutics. In this work, we first time engineered EVs with multivalent cationic lipids for the delivery of nucleic acids. Stable, small size cationized EVs were loaded with plasmid DNA (pDNA), or mRNA, or siRNA. Nucleic acid loaded EVs were efficiently taken up by target cells as demonstrated by confocal microscopy and delivered their cargo to the nuclei in triple negative breast cancer (TNBC) cells and macrophages. Efficient transfection was achieved by engineered cationized EVs formulations of pDNA- and mRNA in vitro. Furthermore, siRNA loaded into cationized EVs showed significant knockdown of the reporter gene in Luc-expressing cells. Overall, multivalent cationized EVs represent a promising strategy for gene delivery.

“Sustainable synthesis of Camellia sinensis-mediated silver nanoparticles (CsAgNP) and their anticancer mechanisms in breast cancer cells”

The present investigation focuses on synthesizing eco-friendly and cost-effective silver nanoparticles (CsAgNP) utilizing Camellia sinensis ethanolic extract (CsE) as a reducing agent and investigating the potential enhancement in its anticancer efficacy as compared to CsE. The CsAgNP formation was confirmed through the color change from pale green to dark brown and further validated using UV–visible spectroscopy in the 400-450 nm range. The optimal CsAgNP synthesis parameters include 1:4 ratio of CsE: 1 mM AgNO3, 60 min of duration and 50 °C reaction temperature. The morphology and the size of nanoparticles were estimated using AFM, SEM and TEM where the results showed a smooth topography with a size <100 nm. The CsAgNP crystalline form was confirmed through SAED pictures and silver's presence confirmed through EDX analysis. FTIR study ascertained the capping agents and distortion in functional groups compared to CsE. The anticancer potency of CsAgNP and crude extract (CsE) was assessed against the T-47D breast cancer cells by MTT assay. CsAgNP displayed strong activity towards T-47D cells (IC50 8 μg/ml) compared to CsE and relatively low activity towards the normal HEK-293 cells. Further, fluorescence microscopy and flow cytometry data revealed that the CsAgNP promotes apoptosis and also induces G2-M phase cell cycle arrest. Furthermore, CsAgNP treatment decreases p53 and Bcl-2 protein expression, while increasing Bax, Cytochrome c and Caspase-3 levels, indicating mitochondrial-mediated apoptotic pathway activation. Thus, our research aims to investigate the potential of using Camellia sinensis to synthesize CsAgNP, a potent drug delivery system, to enhance anticancer effectiveness and advance cancer therapy in the future.

Erratum for the Research Article: "N-terminal signal peptides facilitate the engineering of PVC complex as a potent protein delivery system" by F. Jiang et al.

Erratum for the Research Article: "N-terminal signal peptides facilitate the engineering of PVC complex as a potent protein delivery system" by F. Jiang et al.

Chemically engineered polyethylenimine conjugates for mannose receptor-mediated gene delivery with potential antimicrobial and anticancer activity

Polyethylenimines exhibit unique intrinsic properties, which make them potential gene delivery agents. However, nonspecific interactions and cytotoxicity in the cells/tissues have significantly hampered their use in clinical applications. To subside these concerns, plant-based cyclitols, shikimic and quinic acids, have been tethered to polyethylenimine (PEI) to fabricate shikimoyl-PEI (SP) and quinoyl-PEI (QP) conjugates under mild coupling conditions. On interactions with plasmid DNA, the size and zeta potential of SP and QP complexes were found in the range of ∼245–158 nm and ∼ +22–10 mV, respectively. Subsequent assessment of these complexes revealed that cytocompatibility (∼90%–94%) and transfection efficiency (∼90% cells transfected) were significantly higher as compared to the native PEI/pDNA and Lipofectamine/pDNA complexes. Further, a higher degree of pDNA release was also obtained from SP/DNA and QP/DNA complexes. A decrease in GFP expression was observed in a competitive assay on RAW 264.7 cells, which reflected receptor-mediated internalization of SP and QP/DNA complexes. Besides, both SP and QP conjugates also displayed efficient antimicrobial activity against differential pathogenic strains of bacteria. Of these conjugates, QP conjugates exhibited promising anticancer activity against variable cell lines such as RAW 264.7, MCF-7, HepG2 cells. Altogether, these results advocate the promising potential of SP and QP conjugates as efficient gene delivery agents having effective antimicrobial and anticancer competence.

Rutin loaded bilosomes for enhancing the oral activity and nephroprotective effects of rutin in potassium dichromate induced acute nephrotoxicity in rats

Rutin, a flavone glycoside, has shown to have a significant beneficial kidney protection effect in drug-induced nephropathy. However, its poor solubility and low oral bioavailability have limited its pharmacological applications. This study aimed at formulating rutin-loaded bilosomes to enhance the renal protective effect of rutin for oral application. Rutin-loaded bilosomes were developed using thin-film hydration technique. The prepared formulations were characterized by entrapment efficiency percentage (EE%), vesicular size (VS) and zeta potential (ZP) measurement. The developed formula exhibited moderate EE%, ranging from 20.02 ± 2.85 to 48.57 ± 3.57%, suitable VS results that ranged from 502.1 ± 36 to 665.1 ± 45 nm and high ZP values (≤ -41.4 ± 7.27 mV). Transmission electron microscopy revealed the spherical shape of the developed bilosomes. The in-vitro release study revealed prolonged release of rutin from bilosomes, relative to free drug. F2, prepared using the molar ratio span 60: cholesterol: sodium cholate 1:1:0.5, was selected for further investigations as it showed the highest EE%, smallest VS, optimum ZP, and persistent release profile. In-vivo studies were performed on drug-induced nephropathy in rats. Acute renal failure was induced using a single dose of potassium dichromate (PDC; 15 mg/kg; i.p). The selected formulation, F2, alleviated kidney dysfunction, oxidative stress and inflammation via decreasing MDA, TNF-α and TGF-β and increasing GSH. In addition, F2 promoted Akt/PI3K activation against PDC-induced acute renal failure. Histopathology results came in accordance with in-vivo results. Thus, bilosomes could be considered a potential delivery system for enhancing the oral delivery and kidney protection activity of rutin.

Intranasal administration of liposomes: Potential brain delivery with prospective ophthalmic reach

The low efficacy of drug transportation from the bloodstream to specific tissues remains a challenge in drug delivery to the central nervous system (CNS), primarily because of the presence of the blood-brain and blood-retinal barriers. There is a need for non-invasive drug delivery techniques to the CNS given the intrusive nature of and potential patient burden associated with intraventricular, intrathecal, and intravitreal administration. Recently, the focus has shifted towards intranasal (i.e., nose-to-brain) drug delivery. Furthermore, there have been reports indicating that the use of drug nanocarriers, such as liposomes, facilitates efficient drug delivery via the intranasal pathway. This study investigates the brain penetration capabilities of intranasally administered liposomes using the hydrophobic fluorescent molecule, 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl lindodicarbocyanine, 4-chlorobenzene sulfonate salt (DiD), as a model compound. The primary objective of this study was to elucidate the penetration of intranasally administered liposomes into the CNS, including the eyes. An examination of DiD distribution in the dissected brain and ocular tissues showed that DiD concentrations were elevated specifically at the limbus of the ocular tissue when surface-modified liposomes were employed. These findings suggest that intranasal liposome administration can deliver drugs to the posterior ophthalmic region, specifically the optic nerve, in addition to the brain.

Entrapment of multi-scale structure of alginate beads stabilized with cellulose nanofibrils for potential intestinal delivery of lactic acid bacteria

Soybean cellulose nanofibrils (SCNFs) were formed by autoclave-enzymatic hydrolysis combined with ball milling. SCNFs were blended with sodium alginate (SA) to encapsulate lactic acid bacteria (LAB) through inotropic gelation. The effect of SCNFs on the multiscale structure of SA beads, leading to changes in the survival and release of LAB during simulated digestion, was investigated. Microscopy and rheological testing indicated that SCNF10–30 was well-dispersed in the SA paste in the form of interlaced nanofibrils, and could reduce the deformation of the paste under stress by 47.31 %. Multiscale structural analysis indicated SCNF10–30 not only increased the immobilized water of SA beads by 15.59 % by coordinating calcium, but also regulated the in situ-assembly of SA beads, including an increase in the scale of dimers from 6.73 nm to 8.32 nm and improved arrangement, thus forming a dense gel network. LAB viability of SA-SCNF10–30 in simulated digestion was increased by 1.3 log CFU/g compared to SA beads. Cellulose nanofibrils improved gastrointestinal survival and controlled release of LAB better than fiber rods. This study provides a strategy to regulate the multiscale structure of SA beads through nanofibrils to enable stabilization and sustainable release of LAB in gastrointestinal fluids.

Development of a vocational rehabilitation intervention to support return-to-work and well-being following major trauma: a person-based approach

ObjectivesMajor trauma centres (MTCs) save lives but rehabilitation to support return-to-work (RTW) is lacking. This paper describes development of a vocational rehabilitation intervention (the ROWTATE intervention) to support RTW following...

Recent opportunities and application of gellan gum based drug delivery system for intranasal route.

In the recent years, in-situ hydrogel based on gellan gum has been investigated for delivery of various drug molecules particularly to treat neurological disorders via intranasal route. The major objective of the present manuscript is to review the recent research studies exploring gellan gum as ionic triggered in-situ gel for intranasal administration to enhance absorption of drugs and to increase their therapeutic efficacy. This review include literature from 1982 to 2023 and were collected from various scientific electronic databases like Scopus, PubMed and Google Scholar to review source, chemistry, ionotropic gelation mechanism, and recent research studies for gellan gum based in-situ hydrogel for intransasl administration.Keywords such as gellan gum, in-situ hydrogel, intranasal administration and brain targeting were used to search literature. The present review included the research studies which explored gellan gum based in-situ gel for intranasal drug delivery. The findings have shown enhanced biavailability of various drugs upon intranasal administration using gellan-gum based in-situ hydrogel.Moreover, the review indicated that intranasal administration of in-situ hydrogel facilitate to overcome blood brain barrier effectively. Hence, significantly higher drug concentration was found to be achieved in brain tissues upon intranasal administration than that of other routes like oral and intravenous. The present work conducted a comprehensive review for gellan gum based in-situ hydrogel particularly for intransal administration to overcome BBB. The study concluded that gellan gum based in-situ hydrogel could be potential promising delivery system for intranasal administration to improve bioavailability and efficacy of drugs specifically to treat neurological disorders.

Combinatorial Synthesis of Alkyl Chain-Capped Poly(β-Amino Ester)s for Effective siRNA Delivery.

Poly (β-amino ester) (PBAE) is a class of biodegradable polymers containing ester bonds in their main chain, extensively investigated as cationic polymer carriers for siRNA. Most current PBAE carriers rely on termination with hydrophilic or charged amines. In this study, a polymer platform consisting of 168 PBAE polymers with hydrophobic alkyl chain terminals is constructed through sequential aza-Michael addition. A large number of effective carriers are identified through in vitro screening of the PBAE platform for siLuc delivery to HeLa-Luc cells. Specifically, PA8-C6 and PA8-C8 achieve remarkable gene knockdown efficacies of up to 80% with low cytotoxicity. Certain materials from the PA2 and PA5 series demonstrate potent siRNA delivery capabilities associated with elevated cytotoxicity. The pKa value of PBAE is predominantly determined by the hydrophilic amine side chains rather than the end-capping groups. A pKa range of ≈6.2-6.5 may contribute to the excellent delivery capability for PA8 series carriers. The co-formulation of PBAE carriers with helper lipids leads to the reduced size and surface charges of the polyplex NPs with siRNA, consequently decreasing the cytotoxicity and enhancing siRNA delivery efficacy. These findings hold significant implications for the development of novel degradable polymer carriers for siRNA delivery.

FastAd: A versatile toolkit for rapid generation of single adenoviruses or diverse adenoviral vector libraries

Adenoviruses (Ads) are potent gene delivery vectors for in vitro and in vivo applications. However, current methods for their construction are time-consuming and inefficient, limiting their rapid production and utility in generating complex genetic libraries. Here, we introduce FastAd, a rapid and easy-to-use technology for inserting recombinant “donor” DNA directly into infectious “receiver” Ads in mammalian cells by the concerted action of two efficient recombinases: Cre and Bxb1. Subsequently, the resulting mixed recombinant Ad population is subjected to negative selections by flippase (FLP) recombinase to remove viruses that missed the initial recombination. With this approach, recombinant Ad production time is reduced from two months to 10 days or less. FastAd can be applied for inserting complex genetic DNA libraries into Ad genomes, as evidenced by the generation of barcode libraries with over 3 million unique clones from a T25 flask-scale of transfection. Furthermore, we leveraged FastAd to construct an Ad library containing a comprehensive genome-wide CRISPR/Cas9 guide RNA (gRNA) library and demonstrated its effectiveness in uncovering novel virus-host interactions. In summary, FastAd enables the rapid generation of single Ad vectors or complex genetic libraries, facilitating not only novel applications of Ad vectors but also research in foundational Ad biology.

Chitosan-melanin complex microsphere: A potential colonic delivery system for protein drugs

The characteristics and performance of chitosan-based colon delivery systems are significantly influenced by the method of preparation. Insect chitosan-melanin complex (CMC) may offer superior attributes over traditional shrimp and crab chitosan (CS) for colon-targeted administration. This study used dung beetle CMC as the carrier matrix and comprehensively examined the impact of various crosslinking techniques on the colonic drug delivery efficacy of microspheres, encompassing drug loading, swelling, drug release behavior, adhesion, enzymatic degradation, and absorption enhancement. The results indicate that F-TPPLC microspheres, crosslinked with a combination of formaldehyde and TPP, exhibit superior drug loading capabilities, optimal swelling behavior, and controlled in vitro drug release profiles in the colonic environment, along with excellent adhesion and enzymatic degradation properties within intestinal tract. Notably, these F-TPPLC microspheres increase paracellular permeability, possibly by disrupting the calcium-dependent adhesion junctions. In comparison to commercial CS, CMC demonstrates superior drug encapsulation efficiency, enhanced colonic drug release, adhesion, and absorption promotion, rendering it a favorable candidate as a carrier in colon-targeted drug delivery systems. Consequently, F-TPPLC microspheres derived from CMC are highly suitable for colon drug delivery applications and show promising potential for the oral delivery of peptide and protein-based therapeutics to the colon.

Examining the Influence of the Route of Administration and Dose of Estradiol on Serum Estradiol and Testosterone Levels in Feminizing Gender-Affirming Hormone Therapy

IntroductionIndividuals may seek gender-affirming hormone therapy (GAHT) to align their physical appearance with their gender identity. Feminizing GAHT typically involves the use of estrogen. This study investigates the effect of route of administration (ROA) and dose of estradiol on estradiol (E2) and testosterone (T) levels in transfeminine individuals. MethodsWe conducted a chart review of 573 patients with an active prescription for estradiol for feminizing GAHT and serum hormone levels available. Multiple linear regression and ANOVA were used to analyze the effect of dose and ROA of estradiol on serum E2 and T. ResultsOral estradiol was the only ROA demonstrating a linear dose-response, with each 1 mg/d increase associated with a reduction in T of 19.03 ng/dL (P = .005). Lower T levels were seen with higher doses of transdermal estradiol but a significant dose-response was not demonstrated. Intramuscular estradiol was associated with lower T and higher E2 compared to oral and transdermal ROAs (P < .001), with many achieving target hormone levels even at low doses. With higher oral estradiol doses, ANOVA detected dose-dependent decreases in mean serum LH and FSH (P < .05). ConclusionOral estradiol can be titrated to achieve a stepwise decrease in serum T. The intramuscular ROA appears to be the most potent delivery of estradiol with impact on serum hormone levels with doses on the low end of guideline-suggested ranges. Serum T may be a more reliable biomarker than E2 for managing feminizing GAHT. Serum LH and FSH may also help with the management of feminizing GAHT.

Minimizing Oxidative Stress in the Lens: Alternative Measures for Elevating Glutathione in the Lens to Protect against Cataract.

Oxidative stress plays a major role in the formation of the cataract that is the result of advancing age, diabetes or which follows vitrectomy surgery. Glutathione (GSH) is the principal antioxidant in the lens, and so supplementation with GSH would seem like an intuitive strategy to counteract oxidative stress there. However, the delivery of glutathione to the lens is fraught with difficulties, including the limited bioavailability of GSH caused by its rapid degradation, anatomical barriers of the anterior eye that result in insufficient delivery of GSH to the lens, and intracellular barriers within the lens that limit delivery of GSH to its different regions. Hence, more attention should be focused on alternative methods by which to enhance GSH levels in the lens. In this review, we focus on the following three strategies, which utilize the natural molecular machinery of the lens to enhance GSH and/or antioxidant potential in its different regions: the NRF2 pathway, which regulates the transcription of genes involved in GSH homeostasis; the use of lipid permeable cysteine-based analogues to increase the availability of cysteine for GSH synthesis; and the upregulation of the lens's internal microcirculation system, which is a circulating current of Na+ ions that drives water transport in the lens and with it the potential delivery of cysteine or GSH. The first two strategies have the potential to restore GSH levels in the epithelium and cortex, while the ability to harness the lens's internal microcirculation system offers the exciting potential to deliver and elevate antioxidant levels in its nucleus. This is an important distinction, as the damage phenotypes for age-related (nuclear) and diabetic (cortical) cataract indicate that antioxidant delivery must be targeted to different regions of the lens in order to alleviate oxidative stress. Given our increasing aging and diabetic populations it has become increasingly important to consider how the natural machinery of the lens can be utilized to restore GSH levels in its different regions and to afford protection from cataract.

Effect of gelled phases on the relevance of double emulsion gels for probiotics encapsulation, rheological properties, and stability

This study aimed to develop a stable double emulsion gel (DEG) based on whey protein cold-set gelation of the external water phase and carnauba wax-based solidification of the oil phase as a potential delivery system for probiotics in high-protein food products. The effect of the gelation of different phases on the microstructure, gel properties, and stability of DEGs under storage and freezing–thawing conditions and the viability of L. plantarum loaded in the inner water phase of DEGs were evaluated. The oil phase crystallization allowed the formation of stable DEGs during storage, showing negligible changes in consistency index, G′, and particle size after 56 d of storage and under four freeze–thaw cycles. The gelation of both the oil and external water phases allowed a stronger gel network formation, with a six times lower creaming index than non-gelled double emulsions. All samples demonstrated that the encapsulation of L. plantarum into the inner water phase of the DEG is beneficial for the storage stability of probiotics.

Modified Release Interpenetrating Polymeric Network Hydrogel Beads of Montelukast Sodium Via Box Behnken Design

Background: Interpenetrating Polymeric Networks (IPN) are cross-linked polymeric alloys developed when two or more cross-linked polymers inter-penetratingly entangle. Interpenetrating polymeric networks possess several benefits including stability, biocompatibility, biodegradability, high swelling ability, and modified release efficiency. Aim: The aim of this study is to design stable, control-released montelukast sodium-loaded IPN hydrogel beads as a promising approach toward drug delivery. Objective: The goal of the present work was to develop Chitosan (swellable polymer) and glutaraldehyde (cross-linker) based modified (controlled) released montelukast sodium IPN hydrogel beads. Methods: The montelukast sodium IPN hydrogel beads were prepared via the precipitation method, and the final batch of IPN hydrogel beads was based on particle size, percent entrapment efficiency, area of swelling, and cumulative percent drug release using an overlay plot in Box-Behnken design. Compatibility studies (DSC, FT-IR) and microscopical observation (SEM) confirmed the compatibility and sphericity of the formulations. Results: The optimized (comprising 2.01% chitosan and 0.48% glutaraldehyde) IPN hydrogel beads having satisfactory particle size (817.76±54.49 μm), good entrapment efficiency (71.36±3.04%), and area of swelling (27.00±1.68 mm2) showed swelling and pH-dependent controlled montelukast release (92.96±1.05%) after 12 h with longer duration of action. Conclusion: The prepared montelukast sodium IPN hydrogel beads could be a potent control-released drug delivery vehicle.

Approach of nanostructured lipid carriers (NLCS): tool as a new targeted drug delivery system: A review

The most significant advancement in the creation of more efficient medicine delivery systems has come from nanotechnology. The target drug delivery system is now incredibly simple and efficient thanks to cutting-edge nanotechnology. A target drug delivery system is a technique for getting the medication's active ingredient to the body's injured area. Nanostructured lipid carriers (NLC) are an exceptional and unique development in the field of nanotechnology. Site-specific drug delivery systems can be constructed using NLCs, a novel form of second generation emulsion system that combines spatially incompatible liquid lipids with a mixture of solid lipids. This potential delivery mechanism provides longer stability than SLNs. Because of the potential advantages of drug design at the nanoscale, such as the capacity to increase immunogenicity and bioavailability, which can lead to the development of more convenient administration routes, fewer side effects, improved biodistribution, and an extended drug life cycle, the application of nanostructured and nanophases is seen to bridge the gap between biological and physical sciences.

Inhalable nano-structured microparticles for extracellular matrix modulation as a potential delivery system for lung cancer

The use of inhalable nanoparticulate-based systems in the treatment of lung cancer allows for efficient localized delivery to the lungs with less undesirable systemic exposure. For this to be attained, the inhaled particles should have optimum properties for deposition and at the same time avoid pulmonary clearance mechanisms. Drug delivery to solid tumors is furthermore challenging, due to dense extracellular matrix (ECM) formation, which hinders the penetration and diffusion of therapeutic agents. To this end, the aim of the current work is to develop an ECM-modulating nano-structured microparticulate carrier, that not only enables the delivery of therapeutic nanoparticles (NPs) to the lungs, but also enhances their intratumoral penetration. The system is composed of acetalated maltodextrin (AcMD) NPs embedded into a water-soluble trehalose/leucine matrix, in which collagenase was loaded with different mass concentrations (10 %, 30 % and 50 %). The collagenase-containing AcMD nano-structured microparticles (MPs) exhibited suitable median volume diameters (2.58 ± 1.35 to 3.01 ± 0.68 µm), hollow corrugated morphology, sufficient redispersibility, low residual moisture content (2.71 ± 0.17 % to 3.10 ± 0.20 %), and favorable aerodynamic properties (Mass median aerodynamic diameter (MMAD): 1.93 ± 0.06 to 2.80 ± 0.10 µm and fine particle fraction (FPF): 68.02 ± 6.86 % to 69.62 ± 2.01 %). Importantly, collagenase retained as high as 89.5 ± 6.7 % of its enzymatic activity after spray drying. MPs containing 10 % mass content of collagenase did not show signs of cytotoxicity on either human lung adenocarcinoma A549 cells or lung MRC-5 fibroblasts. The nanoparticle penetration was tested using adenocarcinoma A549/MRC-5 co-culture spheroid model, where the inclusion of collagenase resulted in deeper penetration depth of AcMD-NPs.

Implementation of Postpartum Nutritional Interventions in Healthcare, Community and eHealth: A Systematic Review.

The efficacy of interventions targeting lifestyle habits, particularly dietary habits, among postpartum women is well established. However, whether these results can be translated into tangible changes in the care and services provided to this population remains unclear. Therefore, the aim is to examine the implementation outcomes of postpartum nutritional interventions delivered in healthcare, community, or eHealth settings. A search was conducted in the MEDLINE, EMBASE, Web of Science, CINAHL, and Cochrane Library databases in July 2024, to identify all relevant studies. Included studies had to report at least 1 of the 8 implementation outcomesstudied: acceptability, adoption, appropriateness, implementation cost, feasibility, fidelity, penetration, and sustainability. Study selection and data extraction were performed by two independent reviewers. Descriptive analysis of reported outcomes was performed. CRD42022351411. Of the 8907 unique studies identified, 26 interventions (24 publications) were included.There was a great heterogeneity among interventions studied and implementation outcomes reported. Acceptability, feasibility, and fidelity were the most studied implementation outcomes. Overall, postpartum nutritional interventions were found to be acceptable and useful, but improvements were suggested by participants, such as more frequent contacts and longer programs. Recruitment, retention, participation, and penetration rates widely varied across studies. Challenges hindering the delivery of nutritional interventions were reported by participants, such as lack of time and the presence of medical conditions following delivery. CONCLUSIONSFOR PRACTICE: This review demonstrates the potential forthe delivery and implementation of nutritional interventions in real-world settings during the postpartum period.

Engineered PLGA Core-Lipid Shell Hybrid Nanocarriers Improve the Efficacy and Safety of Irinotecan to Combat Colon Cancer.

Poly(lactide-co-glycolide) (PLGA) is a biocompatible and biodegradable copolymer that has gained high acceptance in biomedical applications. In the present study, PLGA (Mw = 13,900) was synthesized by ring-opening polymerization in the presence of a biocompatible zinc-proline initiator through a green route. Irinotecan (Ir) loaded with efficient PLGA core-lipid shell hybrid nanocarriers (lipomers, LPs) were formulated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino (polyethylene glycol)-2000] (DSPE-PEG-2000), using soya lecithin, by a nanoprecipitation method, and the fabricated LPs were designated as P-DSPE-Ir and P-DSPE-PEG-Ir, respectively. The formulated LPs were further validated for their physicochemical properties and biological potential for colon cancer application. The potential delivery of a poorly water-soluble chemotherapeutic drug (Ir) was studied for the treatment of colon cancer. LPs were successfully prepared, providing controlled size (80-120 nm) and surface charge (∼ -35 mV), and the sustained release properties and cytotoxicity against CT-26 colon cancer cells were studied. The in vivo biodistribution and tumor site retention in CT-26 xenograft tumor-bearing Balb/C mice showed promising results for tumor uptake and retention for a prolonged time period. Unlike P-DSPE-Ir, the P-DSPE-PEG-Ir LP exhibited significant tumor growth delay as compared to untreated and blank formulation-treated groups in CT-26 (subcutaneous tumor model) after 4 treatments of 10 mg irinotecan/kg dose. The biocompatibility and safety of the LPs were confirmed by an acute toxicity study of the optimized formulation. Overall, this proof-of-concept study demonstrates that the PLGA-based LPs improve the efficacy and bioavailability and decrease neutropenia of Ir to combat colon cancer.