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Novel Drug Delivery Approaches for the Localized Treatment of Cervical Cancer

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Abstract

Cervical cancer (CC) is the fourth leading cancer type in females globally. Being an ailment of the birth canal, primitive treatment strategies, including surgery, radiation, or laser therapy, bring along the risk of infertility, neonate mortality, premature parturition, etc. Systemic chemotherapy led to systemic toxicity. Therefore, delivering a smaller cargo of therapeutics to the local site is more beneficial in terms of efficacy as well as safety. Due to the regeneration of cervicovaginal mucus, conventional dosage forms come with the limitations of leaking, the requirement of repeated administration, and compromised vaginal retention. Therefore, these days novel strategies are being investigated with the ability to combat the limitations of conventional formulations. Novel carriers can be engineered to manipulate bioadhesive properties and sustained release patterns can be obtained thus leading to the maintenance of actives at therapeutic level locally for a longer period. Other than the purpose of CC treatment, these delivery systems also have been designed as postoperative care where a certain dose of antitumor agent will be maintained in the cervix postsurgical removal of the tumor. Herein, the most explored localized delivery systems for the treatment of CC, namely, nanofibers, nanoparticles, in situ gel, liposome, and hydrogel, have been discussed in detail. These carriers have exceptional properties that have been further modified with the aid of a wide range of polymers in order to serve the required purpose of therapeutic effect, safety, and stability. Further, the safety of these delivery systems toward vital organs has also been discussed.

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Data Availability

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Abbreviations

CC:

Cervical cancer

HPV:

Human papilloma virus

Pt(IV):

Platinum (IV)

DCA:

Dichloroacetate

DOX:

Doxorubicin

PLA:

Polylactide

PEO:

Poly (ethylene oxide)

PVA:

Polyvinylalcohol

PEG:

Polyethylene glycol

PCL:

Polycaprolactone

PLGA:

Poly[(d,l)-lactide-co-glycolide]

PLLA:

Poly-L-lactide

PVP:

Polyvinyl pyrrolidone

ICG:

Indocyanine green

MSN:

Mesoporous silica nanoparticles

CA4:

Combretastatin A4

FLU:

Fluorescein

Flu:

Fluorescein sodium

HTLC:

Heat-activated thermosensitive liposome

CDDP:

Cisplatin

SEM:

Scanning electron microscopy

AG:

Andrographolide

TEM:

Transmission electron microscopy

PTCT:

Photothermal chemotherapy

H&E:

Hematoxylin and eosin

PBS:

Phosphate-buffered saline

MWCNT:

Multiwalled carbon nanotubes

5FU:

Fluorouracil

F fibers:

Dual drug-loaded multilayered fibers

S-TEL-PEG-CNPs:

Soluble telmisartan entrapped into PEG-conjugated chitosan nanoparticles

API:

Active pharmaceutical ingredient

GEM-HNPs:

Gemcitabine-loaded hybrid nanoparticles

GEM:

Gemcitabine

AuNPs:

Gold nanoparticles

MTT:

Thiazolyl blue tetrazolium bromide

GNPs-GA:

Gallic acid-conjugated gold nanoparticles

BisBAL NPs:

Neo-Poly gramicidin mixture and bismuth nanoparticles

AgNPs:

Silver nanoparticles

SM:

Snail mucus

AgNP-SM:

Silver nanoparticle-snail mucus nanocomposite powder

CS:

Chitosan

FeGI:

Iron(II) glyconate dehydrate

TV:

Toad venom

SLN:

Solid lipid nanoparticles

NR:

Nanorealgar

TV-SLN:

Toad venom-loaded solid lipid nanoparticles

TV-SLN/NR:

Combination of TV-SLN and NR

NC:

Nanocrystals

NC@PDA-NH2 :

Dopamine-coated nanocrystals followed by acid treatment

PYT:

Phytantriol

SMH:

Sinomenine hydrochloride

PILG:

PYT-based in situ liquid crystal gel

RTX:

Raltitrexed

4 CLH:

Drug-loaded hydrogel containing 4% crosslinker

8 CLH:

Drug-loaded hydrogel containing 8% crosslinker

PAA:

Poly(acrylic acid)

TAX:

Paclitaxel

SVF:

Simulated vaginal fluid

Hac/NaAc:

Acetic acid/sodium acetate

QCS:

N,O-Oleoyl chitosan

Lip-QCS:

QCS incorporated into liposomes

Lip:

Liposomes

Lip-QCS-Cisplatin:

Cisplatin-loaded Lip-QCS

HT:

Hyperthermia

RNA:

Ribonucleic acid

siRNAs:

Small interfering RNA

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Acknowledgements

We would like to express our gratitude to the management of Siksha ‘O’ Anusandhan (Deemed to be University), Bhubaneswar, India, and Department of Biotechnology (DBT), Government of India, under the DBT Builder project with order no. BT/INF/22/SP45078/2022.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Siksha O Anusandhan (Deemed to Be University), Bhubaneswar, Odisha, India

    Ivy Saha, Jitu Halder, Tushar Kanti Rajwar, Ritu Mahanty, Deepak Pradhan, Priyanka Dash, Chandan Das, Vineet Kumar Rai, Biswakanth Kar, Goutam Ghosh & Goutam Rath

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  1. Ivy Saha
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  2. Jitu Halder
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  9. Biswakanth Kar
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Ivy Saha, Jitu Halder, Tushar Kanti Rajwar, Ritu Mahanty, Deepak Pradhan, Priyanka Dash, Chandan Das, Vineet Kumar Rai, Biswakanth Kar, Goutam Ghosh, and Goutam Rath. The first draft of the manuscript was written by Ivy Saha, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Goutam Rath.

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Highlights

• Studies proving that localized drug delivery provides safety toward vital organs are discussed.

• Novel drug delivery approaches for local treatment of cervical cancer are broadly discussed.

• Nanocarriers modified by researchers for enhanced therapeutic effects are discussed.

• Various combination treatment modalities for local delivery are highlighted.

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Saha, I., Halder, J., Rajwar, T.K. et al. Novel Drug Delivery Approaches for the Localized Treatment of Cervical Cancer. AAPS PharmSciTech 25, 85 (2024). https://doi.org/10.1208/s12249-024-02801-1

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