Enhancement of Anti-Tumoral Properties of Paclitaxel Nano-Crystals by Conjugation of Folic Acid to Pluronic F127: Formulation Optimization, In Vitro and In Vivo Study
Nagaraja Sreeharsha,
Samathoti Prasanthi,
Satyavarapu Veera Venkata Naga Satya Mahalakshmi,
Prakash S. Goudanavar,
Nimbagal Raghavendra Naveen,
Buduru Gowthami,
Santosh Fattepur,
Girish Meravanige,
Syed Mohammed Basheeruddin Asdaq,
Md. Khalid Anwer,
Bandar Aldhubiab,
Mohammed Monirul Islam,
Mohammed Habeebuddin,
Mallikarjun Telsang,
Mazen Al Gharsan,
Michelyne Haroun
Affiliations
Nagaraja Sreeharsha
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Hofuf 31982, Saudi Arabia
Samathoti Prasanthi
Department of Pharmaceutics, Sri Venkateswara College of Pharmacy, RVS Nagar, Tirupati Rd, Chittoor 517127, Andhra Pradesh, India
Satyavarapu Veera Venkata Naga Satya Mahalakshmi
Department of pharmacognosy, Vishnu Institute of Pharmaceutical Education and Research, Narsapur, Medak 502313, Telangana, India
Prakash S. Goudanavar
Department of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Mandava 571448, Karnataka, India
Nimbagal Raghavendra Naveen
Department of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Mandava 571448, Karnataka, India
Buduru Gowthami
Department of Pharmaceutics, Annamacharya College of Pharmacy, New Boyanapalli, Rajampet 516126, Andhra Pradesh, India
Santosh Fattepur
School of Pharmacy, Management and Science University, Seksyen 13, Shah Alam 40100, Selangor, Malaysia
Girish Meravanige
Department of Biomedical Sciences, College of Medicine, King Faisal University, Al Hofuf 31982, Saudi Arabia
Syed Mohammed Basheeruddin Asdaq
Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Dariyah, Riyadh 13713, Saudi Arabia
Md. Khalid Anwer
Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Alkharj 11942, Saudi Arabia
Bandar Aldhubiab
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Hofuf 31982, Saudi Arabia
Mohammed Monirul Islam
Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al Hofuf 31982, Saudi Arabia
Mohammed Habeebuddin
Department of Biomedical Sciences, College of Medicine, King Faisal University, Al Hofuf 31982, Saudi Arabia
Mallikarjun Telsang
Department of Surgery, College of Medicine, King Faisal University, Al Hofuf 31982, Saudi Arabia
Mazen Al Gharsan
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Hofuf 31982, Saudi Arabia
Michelyne Haroun
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Hofuf 31982, Saudi Arabia
A brand-new nano-crystal (NC) version of the hydrophobic drug Paclitaxel (PT) were formulated for cancer treatment. A stable NC formulation for the administration of PT was created using the triblock co-polymer Pluronic F127. To achieve maximum entrapment effectiveness and minimal particle size, the formulation was improved using the central composite design by considering agitation speed and vacuum pressure at five levels (coded as +1.414, +1, 0, −1, and −1.414). According to the Design Expert software’s predictions, 13 runs were created and evaluated for the chosen responses. The formulation prepared with an agitation speed of 1260 RPM and a vacuum pressure of 77.53 mbar can meet the requirements of the ideal formulation in order to achieve 142.56 nm of PS and 75.18% EE, according to the level of desirability (D = 0.959). Folic acid was conjugated to Pluronic F127 to create folate receptor-targeted NC. The drug release profile of the nano-crystals in vitro demonstrated sustained release over an extended period. Folate receptor (FR)-targeted NC (O-PT-NC-Folate) has also been prepared by conjugating folic acid to Pluronic F127. MTT test is used to validate the targeting efficacy on the FR-positive human oral cancer cell line (KB). At pharmacologically relevant concentrations, the PT nano-crystal formulation did not cause hemolysis. Compared to non-targeted NC of PT, the O-PT-NC-Folate showed a comparable but more sustained anti-cancer effect, according to an in vivo anti-tumor investigation in NCI/ADR-RES cell lines. The remarkable anti-tumor effectiveness, minimal toxicity, and simplicity of scale-up manufacturing of the NC formulations indicate their potential for clinical development. Other hydrophobic medications that are formulated into nano-systems for improved therapy may benefit from the formulation approach.
