Delivery Of Hydrophobic Anticancer Drugs Research Articles

Redox-Responsive Gold Nanoparticles Coated with Hyaluronic Acid and Folic Acid for Application in Targeting Anticancer Therapy.

Methotrexate (MTX) has poor water solubility and low bioavailability, and cancer cells can become resistant to it, which limits its safe delivery to tumor sites and reduces its clinical efficacy. Herein, we developed novel redox-responsive hybrid nanoparticles (NPs) from hyaluronic acid (HA) and 3-mercaptopropionic acid (MPA)-coated gold NPs (gold@MPA NPs), which were further conjugated with folic acid (FA). The design of FA-HA-ss-gold NPs aimed at enhancing cellular uptake specifically in cancer cells using an active FA/HA dual targeting strategy for enhanced tumor eradication. MTX was successfully encapsulated into FA-HA-ss-gold NPs, with drug encapsulation efficiency (EE) as high as >98.7%. The physicochemical properties of the NPs were investigated in terms of size, surface charges, wavelength reflectance, and chemical bonds. MTX was released in a sustained manner in glutathione (GSH). The cellular uptake experiments showed effective uptake of FA-HA-ss-gold over HA-ss-gold NPs in the deep tumor. Moreover, the release studies provided strong evidence that FA-HA-ss-gold NPs serve as GSH-responsive carriers. In vitro, anti-tumor activity tests showed that FA-HA-ss-gold/MTX NPs exhibited significantly higher cytotoxic activity against both human cervical cancer (HeLa) cells and breast cancer (BT-20) cells compared to gold only and HA-ss-gold/MTX NPs while being safe for human embryonic kidney (HEK-293) cells. Therefore, this present study suggests that FA-HA-ss-gold NPs are promising active targeting hybrid nanocarriers that are stable, controllable, biocompatible, biodegradable, and with enhanced cancer cell targetability for the safe delivery of hydrophobic anticancer drugs.

Lauric acid-based thermosensitive delivery system for the treatment of head and neck squamous cell carcinoma

Traditional treatments for head and neck squamous cell carcinoma (HNSCC) such as surgery, radiation therapy, and chemotherapy, often have severe side effects. Local delivery of chemotherapeutic agents can be a promising approach to minimise systemic toxicity and improve efficacy. Lauric acid (LA), was explored as a novel injectable thermosensitive drug reservoir as a depot for sustained release of anticancer drugs to treat HNSCC. LA was characterised in terms of melting temperature and gelation time. The efficacy of LA-based drug formulations was tested in vitro in a HNSCC cell line and in vivo in a mouse model of HNSCC. LA was modified to have a melting point of 38.5 °C and a gelation time of 40 s at 37.5 °C, rendering it suitable for injection at body temperature. LA- based doxorubicin (DOXO) formulation showed slow release with a maximum of 18% release after 3 days. The in vitro study showed that LA enhanced the cytotoxic effect of DOXO. LA combined with DOXO prevented tumour progression and LA alone significantly reduced the original tumour volume compared to the untreated control group. These findings confirmed that LA can function as practical carrier for the local delivery of chemotherapeutics and provides a safe and simple strategy for the delivery of hydrophobic anticancer drugs and warrant further testing in clinical trials.

Synthesis and characterization of the redox-responsive amphiphilic fluorescent alginate derivatives as the multi-functional hydrophobic anticancer drug delivery system with visualization and sustained release

To develop the multi-functional hydrophobic anticancer drug carriers with visualization and sustained release, a novel amphiphilic alginate derivative (LSA-SS-DEAC) containing chromophobe groups was designed and synthesized by grafting hydrophobic fluorescent molecule, 7-(diethylamino-coumarin-3-carboxylic acid (DEAC-COOH) onto hydrophilic low molecular alginate backbone through cystamine by water-soluble carbodiimide chemical method. The molecular structure and self-assembly properties of the synthesized LSA-SS-DEAC were characterized. Furthermore, the encapsulation of anti-cancer drugs, doxorubicin hydrochloride (DOX) in LSA-SS-DEAC self-assembled micelles was realized by ultrasonic dialysis method. Subsequently, the in vitro drug release behavior and in vitro cytotoxicity of LSA-SS-DEAC micelles in simulated tumor microenvironment were also studied. The resultant LSA-SS-DEAC with the critical micelle concentration (CMC) of 0.26 mg/mL exhibited the ability to spontaneously form spherical micelles with the particle size of 250.2 ± 4.3 nm (PDI = 0.23) and zeta potential of −49.1 ± 0.4 mV, which presented good stability in pH 7.4 PBS and excellent fluorescence properties and redox responsiveness. The drug-loaded LSA-SS-DEAC micelles had the optimal EE value of about 42.2% when the DOX/LSA-SS-DEAC mass ratio was 3:10. Meanwhile, The drug-loaded LSA-SS-DEAC micelles exhibited sustained release in GSH-free environment, and the cumulative drug release rates were 40.3% and 46.6% in pH 7.4 and 5.0 PBS for 48 h, respectively. However, in the simulated tumor cell microenvironment (pH 5.0 PBS + 10 mM GSH), the disulfide bond between the core-shell was broken under the GSH trigger, and the LSA-SS-DEAC micelles collapsed, resulting in a cumulative drug release rate of about 64% at 12 h. In vitro cytotoxicity results showed that LSA-SS-DEAC had low cytotoxicity, and revealed obvious inhibitory effect on HeLa cells after DOX loading. Fluorescence imaging results indicated that LSA-SS-DEAC micelles could emit green light after ingested by cells, and their fluorescence properties were not affected after encapsulation of DOX. Accordingly, LSA-SS-DEAC micelles had the potential for drug localization tracking and rapid drug release at focal sites, which could be expected to be an ideal drug carriers for hydrophobic anticancer drug delivery.

Polyamidoamine dendrimer-mediated hydrogel for solubility enhancement and anti-cancer drug delivery.

The application of hydrogels for anti-cancer drug delivery has garnered considerable interest in the medical field. Current cancer treatment approaches, such as chemotherapy and radiation therapy, often induce severe side effects, causing significant distress and substantial health complications to patients. Hydrogels present an appealing solution as they can be precisely injected into specific sites within the body, facilitating the sustainable release of encapsulated drugs. This localized treatment approach holds great potential for reducing toxicity levels and improving drug delivery efficacy. In this study we developed a hydrogel delivery system containing polyamidoamine (PAMAM) dendrimer and polyethylene glycol (PEG) for solubility enhancement and sustained delivery of hydrophobic anti-cancer drugs. The three selected model drugs, e.g. silibinin, camptothecin, and methotrexate, possess limited aqueous solubility and thus face restricted application. In the presence of vinyl sulfone functionalized PAMAM dendrimer at 45 mg/mL concentration, drug solubility is increased by 37-fold, 4-fold, and 10-fold for silibinin, camptothecin, and methotrexate, respectively. By further crosslinking of the functionalized PAMAM dendrimer and thiolated PEG, we successfully developed a fast-crosslinking hydrogel capable of encapsulating a significant payload of solubilized cancer drugs for sustained release. In water, the drug encapsulated hydrogels release 30%-80% of their loads in 1-4days. MTT assays of J82 and MCF7 cells with various doses of drug encapsulated hydrogels reveal that cytotoxicity is observed for all three drugs on both J82 and MCF7 cell lines after 48h. Notably, camptothecin exhibits higher cytotoxicity to both cell lines than silibinin and methotrexate, achieving up to 95% cell death at experimental conditions, despite its lower solubility. Our experiments provide evidence that the PAMAM dendrimer-mediated hydrogel system significantly improves the solubility of hydrophobic drugs and facilitates their sustained release. These findings position the system as a promising platform for controlled delivery of hydrophobic drugs for intratumoral cancer treatment.

A generalizable strategy for crosslinkable albumin-based hydrogels and application as potential anti-tumor nanoplatform.

Albumin-based hydrogels have emerged as promising nanoparticle systems for the effective delivery of hydrophobic anticancer drugs. Anti-cancer drugs often cause some adverse effects, such as toxicity and rapid clearance by mononuclear phagocytic systems. Herein, a new strategy of synthesizing N-hydroxysuccinimide (NHS)-activated linker to form crosslinkable albumin-based hydrogels (CABH) is reported. The CABH favored physiochemical characteristics improvement of doxorubicin (Dox) and drug release. The CABH was constructed depending on the crosslinking reaction between NHS activated glycerol and albumin. The size of CABH was approximately 200nm examined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). It was found that the particle size and size distribution of the CABH remained stable in neutral PBS for 1week. Dox loaded CABH would be controllably released in weak acidic environment verified by in vitro release and in vitro cell imaging. The Dox loaded hydrogel results in significant killing in the case of acidic culture medium. Our work provides a crosslinking method to formulate albumin nanoplatform and improve the size, stability, drug loading capacity and controlled release, which throws light on the potential application in drug delivery.

Micelles in Cancer Therapy: An Update on Preclinical and Clinical Status.

In the recent years, Micelles represent a promising carrier for the treatment and diagnosis of cancer. Architecturally, micelles are self-assembled nanosized colloidal aggregates prepared from amphiphilic surfactant with a hydrophobic core and hydrophilic shell. Such a composition makes them a potential carrier for delivery of hydrophobic anticancer drugs with in their core. Micelles have received increasing interest as an enhanced permeability and retention (EPR) targeted drug delivery systems for cancer treatment. Micelles can be modified to contribute various attractive properties, for instance, active targeting, stimuli-responsiveness. They have also proven their ability in drug targeting to tumor tissue, enhanced drug accumulation, drug stabilization, tissue penetration, prolong circulation, in vivo biocompatibility, biodegradability and reduced side effects. Micelles have displayed a vital role in multidrug delivery for cancer therapy. The aim of the present review is to provide an overview on the status of micellar nanoformulations for anticancer agents, including their pre-clinical and clinical researches. Emphasis is placed on presenting the newer strategies to enhance the therapeutic efficacy of anticancer drug at the target site. The type of co-polymers used and methods for the preparation of micelles are also highlighted in the paper.

Erratum to: In situ Forming Hydrogel Crosslinked with Tetronic Micelle for Controlled Delivery of Hydrophobic Anticancer Drug

Erratum to: In situ Forming Hydrogel Crosslinked with Tetronic Micelle for Controlled Delivery of Hydrophobic Anticancer Drug

In situ Forming Hydrogel Crosslinked with Tetronic Micelle for Controlled Delivery of Hydrophobic Anticancer Drug

In situ Forming Hydrogel Crosslinked with Tetronic Micelle for Controlled Delivery of Hydrophobic Anticancer Drug

Hydrophobic modified poly(l‐glutamic acid) graft copolymer micelles with ultrahigh drug loading capacity for anticancer drug delivery

AbstractSelf‐assembled polymeric nanoparticle (NP) drug carriers are capable of encapsulated and controlled delivery, facilitating improvements in the therapeutic efficiency of drugs. Here we report a series of poly(l‐glutamic acid)‐g‐methoxy poly(ethylene glycol)/4‐phenylbutyl ester (PLG‐g‐mPEG/PB) copolymers, which were synthesized by esterification of 4‐phenylbutanol (PB) and PLG‐g‐mPEG in different feed ratios. The copolymers obtained form into nano‐sized micelles in aqueous solution by a self‐assembly process, with lower critical micelle concentration value for higher PB ratio in the copolymers. Variable temperature infrared spectroscopy and circular dichroism were used to prove the breaking of intermolecular hydrogen bonds after PB modification. Podophyllotoxin (PPT), an effective anticancer agent, was incorporated into the inner core of the micelle system by physical entrapment through hydrophobic interaction between the drug and the PB‐modified copolymers. Both the drug loading content and the loading efficiency increased with PB content in the PLG‐g‐mPEG/PB copolymers and reached an ultrahigh value of 28.2 wt% and 94%, respectively. The PPT‐encapsulated micelles (PPT‐NPs) were stable at pH 7.4 but dissociated and released 80% of loaded PPT in a weak acidic environment (pH 5.0). The in vitro proliferation of non‐small‐cell lung cancer cells (A549) was significantly inhibited by PPT‐NPs in a cytotoxicity assay. These results demonstrate that hydrophobic modification is an efficient route for tuning the self‐assembly behaviour and drug encapsulation of PLG‐g‐mPEG copolymers, and our PLG‐g‐mPEG/PB will serve as a promising carrier for hydrophobic anticancer drug delivery. © 2021 Society of Industrial Chemistry.

Alkyl Chain Length in Poly(2-oxazoline)-Based Amphiphilic Gradient Copolymers Regulates the Delivery of Hydrophobic Molecules: A Case of the Biodistribution and the Photodynamic Activity of the Photosensitizer Hypericin.

Self-assembled nanostructures of amphiphilic gradient copoly(2-oxazoline)s have recently attracted attention as promising delivery systems for the effective delivery of hydrophobic anticancer drugs. In this study, we have investigated the effects of increasing hydrophobic side chain length on the self-assembly of gradient copolymers composed of 2-ethyl-2-oxazoline as the hydrophilic comonomer and various 2-(4-alkyloxyphenyl)-2-oxazolines as hydrophobic comonomers. We show that the size of the formed polymeric nanoparticles depends on the structure of the copolymers. Moreover, the stability and properties of the polymeric assembly can be affected by the loading of hypericin, a promising compound for photodiagnostics and photodynamic therapy (PDT). We have found the limitation that allows rapid or late release of hypericin from polymeric nanoparticles. The nanoparticles entering the cells by endocytosis decreased the hypericin-induced PDT, and the contribution of the passive process (diffusion) increased the probability of a stronger photoeffect. A study of fluorescence pharmacokinetics and biodistribution revealed differences in the release of hypericin from nanoparticles toward the quail chorioallantoic membrane, a preclinical model for in vivo studies, depending on the composition of polymeric nanoparticles. Photodamage induced by PDT in vivo well correlated with the in vitro results. All formulations studied succeeded in targeting hypericin at cancer cells. In conclusion, we demonstrated the promising potential of poly(2-oxazoline)-based gradient copolymers for effective drug delivery and sequential drug release needed for successful photodiagnostics and PDT in cancer therapy.

Biotin-decorated all-HPMA polymeric micelles for paclitaxel delivery

To avoid poly(ethylene glycol)-related issues of nanomedicines such as accelerated blood clearance, fully N-2-hydroxypropyl methacrylamide (HPMAm)-based polymeric micelles decorated with biotin for drug delivery were designed. To this end, a biotin-functionalized chain transfer agent (CTA), 4-cyano-4-[(dodecylsulfanylthiocarbonyl)-sulfanyl]pentanoic acid (biotin-CDTPA), was synthesized for reversible addition–fragmentation chain-transfer (RAFT) polymerization. Amphiphilic poly(N-2-hydroxypropyl methacrylamide)-block-poly(N-2-benzoyloxypropyl methacrylamide) (p(HPMAm)-b-p(HPMAm-Bz)) with molecular weights ranging from 8 to 24 kDa were synthesized using CDTPA or biotin-CDTPA as CTA and 2,2′-azobis(2-methylpropionitrile) as initiator. The copolymers self-assembled in aqueous media into micelles with sizes of 40–90 nm which positively correlated to the chain length of the hydrophobic block in the polymers, whereas the critical micelle concentrations decreased with increasing hydrophobic block length. The polymer with a molecular weight of 22.1 kDa was used to prepare paclitaxel-loaded micelles which had sizes between 61 and 70 nm, and a maximum loading capacity of around 10 wt%. A549 lung cancer cells overexpressing the biotin receptor, internalized the biotin-decorated micelles more efficiently than non-targeted micelles, while very low internalization of both types of micelles by HEK293 human embryonic kidney cells lacking the biotin receptor was observed. As a consequence, the paclitaxel-loaded micelles with biotin decoration exhibited stronger cytotoxicity in A549 cells than non-targeted micelles. Overall, a synthetic pathway to obtain actively targeted poly(ethylene glycol)-free micelles fully based on a poly(HPMAm) backbone was established. These polymeric micelles are promising systems for the delivery of hydrophobic anticancer drugs.

In vivo serum enabled production of ultrafine nanotherapeutics for cancer treatment

Systemic delivery of hydrophobic anti-cancer drugs with nanocarriers, particularly for drug-resistant and metastatic cancer, remain a challenge because of the difficulty to achieve high drug loading, while maintaining a small hydrodynamic size and colloid stability in blood to ensure delivery of an efficacious amount of drug to tumor cells. Here we introduce a new approach to address this challenge. In this approach, nanofibers of larger size with good drug loading capacity are first constructed by a self-assembly process, and upon intravascular injection and interacting with serum proteins in vivo, these nanofibers break down into ultra-fine nanoparticles of smaller size that inherit the drug loading property from their parent nanofibers. We demonstrate the efficacy of this approach with a clinically available anti-cancer drug: paclitaxel (PTX). In vitro, the PTX-loaded nanoparticles enter cancer cells and induce cellular apoptosis. In vivo, they demonstrate prolonged circulation in blood, induce no systemic toxicity, and show high potency in inhibiting tumor growth and metastasis in both mouse models of aggressive, drug-resistant breast cancer and melanoma. This study points to a new strategy toward improved anti-cancer drug delivery and therapy.

Micellar assisted aqueous stabilization of iron oxide nanoparticles for curcumin encapsulation and hyperthermia application

Aqueous stabilization of organically modified magnetic nanoparticles is essential for its biomedical applications. We demonstrate an effective procedure of transferring the bare iron oxide (Fe3O4) magnetic nanoparticle (BMNPs) into aqueous medium using mixed micelles comprising sodium dodecyl sulphate (SDS) and aniline hydrochloride (AHC). Small angle X-ray scattering (SAXS) and dynamic light scattering (DLS) studies confirmed that SDS–AHC mixture form rod like or worm like micelles of hydrodynamic diameter of about 9 nm. However, the hydrodynamic diameter of the micelle stabilized Fe3O4 magnetic nanoparticles (MMNPs) is about 120 nm and they showed long-term aqueous stability. Further, they possess surface charge of −31 mV which is conducive for colloidal stability MMNPs at physiological medium. These MMNPs have high loading affinity towards hydrophobic anticancer drug, curcumin (encapsulation efficiency of 58% at curcumin concentration of 0.25 mg/ml) and ability to deliver them in pH responsive manner. They exhibited substantial cellular uptake in breast cancer (MCF-7) cells and have good heating efficiency under AC magnetic field for hyperthermia therapy. Specifically, we have developed micellar stabilized Fe3O4 nanoparticles and investigated their applications in hyperthermia and delivery of hydrophobic anticancer drug.

Chitosan oligosaccharide-based dual pH responsive nano-micelles for targeted delivery of hydrophobic drugs

In this study, chitosan oligosaccharide (COS)-vanillin imine (COS-Vani Imine)-based dual pH responsive nano-micelles (DPRNs) were synthesized. The resultant DPRNs were used for encapsulating genistein and its ultimate release upon pH change. The overall concept of DPRNs for the targeted delivery of hydrophobic anticancer drugs was successfully demonstrated. The DPRNs were spherical in shape, nanoscale in dimension (71.2–163.4 nm), with dual pH response. The encapsulation/loading of genistein into DPRNs was achieved and the resultant genistein-loaded DPRNs were stable under the physiological pH (˜7.4); under the cancer cell extracellular pH (˜6.8), the amino groups in COS is protonated, thus becoming positively charged, facilitating their adsorption onto negatively charged cancer cells. Under the cancer cell intracellular pH (˜5.0), the genistein-loaded DPRNs were destroyed as a result of the cleavage of pH sensitive benzoic imine, thereby releasing the loaded genistein.

Comparison of Polydopamine-Coated Mesoporous Silica Nanorods and Spheres for the Delivery of Hydrophilic and Hydrophobic Anticancer Drugs.

Mesoporous silica nanoparticles (MSNs) have been widely studied as drug delivery systems in nanomedicine. Surface coating of MSNs have enabled them to perform efficiently in terms of bioavailability, biocompatibility, therapeutic efficacy and targeting capability. Recent studies have suggested the use of polydopamine (PDA) as a facilitative coating for MSNs that provides sustained and pH-responsive drug release, owing to the adhesive “molecular-glue” function of PDA. This further endows these hybrid MSN@PDA particles with the ability to carry large amounts of hydrophilic drugs. In this study, we expand the feasibility of this platform in terms of exploring its ability to also deliver hydrophobic drugs, as well as investigate the effect of particle shape on intracellular delivery of both a hydrophilic and hydrophobic anticancer drug. MSN@PDA loaded with doxorubicin (hydrophilic) and fingolimod (hydrophobic) was studied via a systematic in vitro approach (cellular internalization, intracellular drug distribution and cytotoxicity). To promote the cellular uptake of the MSN@PDA particles, they were further coated with a polyethylene imine (PEI)-polyethylene glycol (PEG) copolymer. Drug-loaded, copolymer-coated MSN@PDA showed effective cellular uptake, intracellular release and an amplified cytotoxic effect with both doxorubicin and fingolimod. Additionally, rods exhibited delayed intracellular drug release and superior intracellular uptake compared to spheres. Hence, the study provides an example of how the choice and design of drug delivery systems can be tuned by the need for performance, and confirms the PDA coating of MSNs as a useful drug delivery platform beyond hydrophilic drugs.

Mesoporous NiS2 nanospheres as a hydrophobic anticancer drug delivery vehicle for synergistic photothermal-chemotherapy.

To overcome the unfavorable effects of the hydrophobicity of drugs and cancer resistance, mesoporous NiS2 nanospheres (mNiS2 NSs) have been successfully developed here to package hydrophobic camptothecin (CPT) and realize the synergistic photothermal-chemotherapy of cancer. The mNiS2 NSs which were prepared through a facile solvothermal method here exhibited not only considerable near-infrared (NIR) absorption and good photothermal conversion efficiency as high as 44.6%, but also achieved a NIR light induced CPT release property which were both beneficial for improving the cancer cell-killing efficacy. After a short period of NIR light illumination, a significant intensified cell killing efficacy was observed when 4T1 or HepG2 cancer cells were incubated with CPT@mNiS2 NSs. Thus, mNiS2 NSs have been demonstrated here to have potential as a novel NIR light-responsive hydrophobic drug delivery nanoplatform for realizing synergistic cancer treatment.

A photo-controlled hyaluronan-based drug delivery nanosystem for cancer therapy

In this paper, a novel photo-controlled drug-loaded nanomicelles were self-assembled by the amphiphile of hyaluronan-o-nitrobenzyl-stearyl chain (HA-NB-SC) with doxorubicin (DOX) encapsulated within the hydrophobic core. DOX-loaded HA-NB-SC nanomicelles are ∼139 nm in diameter. CD44-overexpressed HeLa cells can easily take up HA-NB-SC micelles through recognition of HA moiety. DOX-loaded HA-NB-SC nanomicelles could be disassembled upon UV light (365 nm) and consequently, release DOX at desired pathological sites. Furtherly, nitrosobenzaldehyde derivative, photo-induced products of HA-NB-SC and DOX could inhibit the proliferation of HeLa cells together. This strategy may shed some light on delivery of hydrophobic anti-cancer drugs in a controlled manner.

Facile preparation of metal−organic frameworks-based hydrophobic anticancer drug delivery nanoplatform for targeted and enhanced cancer treatment

Nowadays, cancer has been one of the major threats to human beings throughout the world. Nanomedicines have been demonstrated as a promising candidate for cancer chemotherapy. In this work, we facilely constructed a RGD (Arg-Gly-Asp) modified camptothecin@zeolitic imidazolate framework-8 (RGD@CPT@ZIF-8) as a novel metal-organic frameworks-based hydrophobic drug delivery system for targeted and enhanced cancer treatment. In our system, the nanoplatform exhibited the superior property of target to the cancer cells due to the function with RGD. More importantly, the RGD@CPT@ZIF-8 nanoplatform has shown the enhanced cancer cell treatment due to the excellent pH-responsive hydrophobic anticancer drug delivery and intracellular ROS generation. With the excellent targeting and enhanced therapy performance, we envision that the hydrophobic anticancer drug delivery system could become a potential therapeutic agent for targeted cancer treatment.

PSMA Antibody-Conjugated Pentablock Copolymer Nanomicellar Formulation for Targeted Delivery to Prostate Cancer.

The main purpose of this study was to develop a prostate-specific membrane antigen (PSMA) antibody-conjugated drug-loaded nanomicelles using MPEG--PLA-PCL-PLA-PEG-NH2 pentablock copolymer for targeted delivery of hydrophobic anticancer drugs to prostate cancer cells. During this experiment, monomers of L-lactide, ε-caprolactone, poly(ethylene glycol)-methyl ether, and poly(ethylene glycol)-NH2 were used to prepare pentablock copolymer using the ring opening technique. The pentablock nanomicellar (PBNM) formulation was prepared by the evaporation-rehydration method. The resultant pentablock nanomicelles were then conjugated with PSMA antibody resulting in PSMA-Ab-PTX-PBNM. Both the block copolymers and the nanomicelles were analyzed by hydrogen nuclear magnetic resonance (H-NMR), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The obtained nanomicelles (NM) were then analyzed for size and zeta potential using dynamic light scattering-dynamic laser scattering (DLS) and then further submitted to H-NMR and TEM analyses. The XRD, FTIR, and the H-NMR analyses confirmed the structure of the pentablock copolymers. The average size for conjugated nanomicellar was 45nm ± 2.5nm. The average (ζ-potential) was around - 28mV. H-NMR and FTIR analysis done on PSMA-coupled paclitaxel-loaded PBNM showed peaks characteristic of the drug (paclitaxel) and the polymer, confirming the successful encapsulation. TEM analysis showed well-defined spherical morphology and confirmed the size range obtained by the DLS. In vitro release studies revealed sustained slow of PTX in phosphate buffer solution (PBS). Confocal scanning microscopy (TEM) of coumarin6-loaded in PBNM indicated that pentablock nanomicelles were internalized into the prostate cancer (PC-3) cells. Cell proliferation assay showed that nanomicelles ferried paclitaxel into the PC-3 cells and subsequently reduced the cell proliferation. The results depict PTX-PBNM-Ab as a suitable carrier for targeted delivery of drugs to prostate cancer cells.

Novel amphiphilic heparin-pluronic P123 copolymers exhibiting a great potential for Cisplatin delivery

In the study, we introduced a series of amphiphilic pluronic P123-conjugated heparin (hep-P123) copolymers which were characterized for drug delivery. In regard to the research, various grafted hep-P123 copolymers investigated its potential in the delivery of hydrophobic Cisplatin (Cis) anticancer drugs and its aquated species (CisOH) via hydrophobic interaction and complex formation, respectively. Hep-P123 was obtained via conjugation of the partially NPC-activated pluronic P123 (NPC-P123-OH) onto the aminated heparin (hep-DAB). The obtained copolymers were characterized by 1H-NMR and thermal gravimetric analysis. The effect of P123 conjugation degree on size distribution of nanocarriers was evaluated by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The results showed that size distribution of hep-P123 nanogels range from 62.2 ± 19.4 nm to 114.5 ± 21.7 nm by TEM and 94.4–182.4 nm by DLS. Complex formation of the CisOH was clarified by FT-IR. Loading efficiency of Cis/CisOH was evaluated by inductively coupled plasma atomic emission spectroscopy that indicated a relation between the conjugated degree of hep-P123 and amount of loaded drugs. In addition, hep-P123 exhibited a higher CisOH binding efficiency via complexation as compared to the loaded Cis by hydrophobic interaction. The CisOH and hep-P123 nanocomplex performed a high activity against NCI-H460 cancer cell growth. The obtained results offered an appropriate selection of the hep-P123 platform for dual drugs delivery of CisOH and other hydrophobic anticancer drugs which could utilize both hydrophobic interaction and complex formation.