Chitin and Chitosan Drug Delivery Application, Recent Advances and Clinical Pertinence in Transdermal Drug Delivery System

 

Shaik Harun Rasheed¹, Vajrala Leela Lakshmi², Yeduru Krishna Reddy³*, Rajana James⁴,

G. Buela Priyanka⁵, Ch. Saibabu⁶, K.H.Usha Devi⁷

¹Department of Pharmaceutics, School of Pharmacy, Guru Nanak Institutions Technical Campus (Autonomous), Ibrahimpatnam, Hyderabad - 501506, Telangana, India

²Department of Pharmaceutics, Narayana Pharmacy College, Nellore - 524003, Andhra Pradesh, India

^3,4Department of Pharmaceutics, Royal Global University, Guwahati - 781035, Assam, India

⁵Department of Pharmaceutics, School of Pharmacy, Guru Nanak Institutions Technical campus (Autonomous), Ibrahimpatnam, Hyderabad - 501506, Telangana, India

⁶Department of Pharmaceutics, Malineni Lakshmaiah College of Pharmacy,

Singarayakomda, Andhra Pradesh - 523101, India

⁷Department of Pharmacy Practice, Guru Nanak Institutions Technical Campus (Autonomous),

School of Pharmacy Campus, Ibrahimpatnam, Hyderabad - 501506, Telangana, India.

 

ABSTRACT:

Polymers play a crucial role in drug delivery systems by enabling the encapsulation and controlled release of therapeutic agents. In comparison to synthetic counterparts, naturally derived polymers offer notable benefits, including superior biocompatibility, biodegradability, and the presence of recognizable functional groups that support cellular interactions. Chitosan, a polysaccharide obtained from chitin, has recently attracted significant interest due to its non-toxic nature and favorable biological properties. It exhibits excellent biocompatibility, biodegradability, stability, and antimicrobial activity. Additionally, chitosan demonstrates versatile characteristics such as adjustable drug release behavior, ease of chemical modification, compatibility with other polymers through crosslinking, antibacterial effects, bioadhesive properties, immune system stimulation, macrophage activation, and gas permeability. This work highlights the role of chitosan in drug delivery applications and discusses the key properties of chitin and chitosan along with various drug release mechanisms.

 

 

INTRODUCTION: 

Transdermal route finds application in different clinical situations to avoid the considerable disadvantages of the oral method of medication delivery¹. Recent breakthroughs in this field reveal the importance of transdermal drug delivery systems which are unable to diffuse or be diffused through the skin by external and internal means respectively. It has been an easy way of transporting high molecular weight agents. It is also prepared to avoid pain-related issues and at the same time are injected with hypodermic needles². In this article, we explain conditions, uses and recent developments in transdermal technique of administering the molecules. The low potency of a therapeutic agent has been studied on how to counter this in different manners. Future research will consider how to enhance transdermal architecture to maximize drug delivery along with minimizing loss during preparation and stacking³, to enable transdermal therapy to be cheaper and more accessible, primarily to developing countries. Though interest in studying transdermal drug delivery system is escalating every year, the disadvantages of systems must be taken seriously. This would help transdermal enter the possible market and be able to pass the clinical pertinence test. Some transdermal drug delivery devices are undergoing clinical trials at Phase III but; transdermal has not proven its clinical relevance in vaccination⁴. Consequently, there has been progress in trying to administer the drug through a transdermal method, which is currently being seen as an effective substitute to the use of hypodermic needles. This paper highlights the potential therapeutic and safety advantages of using these systems to administer drugs transdermally and their more recent advances and clinical utility⁵.

 

BEYOND TRANSDERMAL DRUG DELIVERY:

It was estimated that the market of drug delivery is worth 440.5 billion USD in 2025-2026.In particular, injectables has been found to be particularly effective considering cost, bioavailability, and rapid action. These methods have been very important in the distribution of biological macromolecules, insulin, vaccinations and dots among others. However, due to their invasiveness, stability issues, and nonconformity, they began to raise questions and have compelled the introduction of well-prepared medical practitioners⁶. Replacement of all these needles has been contemplated using some measures but the improvements required could not be done. Traditional forms of transdermal delivery of medications have existed about 50 years. These have been effective in supplying various drugs including testosterone, nicotine, selegiline and clonidine. These methods of medication delivery have been proven to be painless, effective and pain-free. Their ability to deliver most of the important macromolecules was however limited by their slower action onset, only being able to deliver molecules with lower molecular weight, and being lipophilic. To some extent, the techniques, such as penetration enhancers, iontophoresis, and sonophoresis could meet the objective, but efficient medication administration that did not breach the needs of the patients remained a top priority. These techniques are being developed in particular to deliver biological macromolecules such as insulin, growth hormones, immunobiological proteins, siRNA, and peptides. Micro needle has been utilized widely since it has been studied. Considering the aspects of clinical trials-based microneedle technologies in the context of frequency of their entry into the global market it has been observed that they can greatly transform the global transdermal business arena⁷.

 

 

Figure 1. Transdermal Drug Delivery System Marketed, Size by Product, 2013-2022

 

DRUG RELEASE AND KINETICS:

Similar to any other dosage form, the liberation of drugs through chitosan-based dosage system is as well determined by the physicochemical property of the drug contained. The hydrophobicity or hydrophobicity, partition coefficient, size and dosage, bio adhesion to mucin or skin, ability to swell and develop a gel in various body fluids in different PH values and ionic concentrations and the presence of the above mechanisms in drug release of chitosan-based dosage forms: diffusion, swelling, erosion, biodegradation and three others⁸.

 

APPLICATIONS:

The use of chitosan and its derivatives as drug delivery methods has been the subject of several publications in recent years. Besides the noninvasive delivery methods, such as transdermal, buccal, nasal, pulmonary or vaginal mucosa, invasive methods of drug delivery, such as parenteral route, are also addressed by these drug delivery systems. Vesicle and nanoparticle drug delivery systems have frequently been employed in parenteral therapy, allowing drugs to be delivered to specific target locations, or to enhance the longevity of the delivery system against phagocytosis⁹. Almost every drug delivery mechanism has been utilized in non-invasive surgery geared towards enhancing mucoadhesion or extending drug release duration. This is because of its cationic character and low solubility in water solutions. The following describes the many routes of administration for chitosan and its derivatives¹⁰.

 

Table 1: Ingredients used in transdermal medication delivery system preparation list

S. No	Polymer	Matrix polymer
1	HPMC	PVP
2	HPMC	Ethyl cellulose
3	HPMC	Eudragit L 100
4	HPMC	Carbopol
5	HPMC	CAP

 

Figure 2. Applications for transdermal medication delivery

 

TRANSDERMAL MEDICATION DELIVERY SYSTEM IDEAL PROPERTIES:

Low molecular weight (less than 1000 Da), affinity for lipophilic and hydrophilic phases, low melting point, short half-life, and non-irritating qualities are desirable characteristics of medications intended for transdermal delivery^11,12.

 

TRANSDERMAL MEDICATION DELIVERY SYSTEM USE POLYMER:

Natural polymers include things like chitosan, cellulose derivatives, zein, gelatin, shellac, waxes, gums, and natural rubber.

 

Polybutadiene, hydrin rubber, polyisobutylene, silicon rubber, nitrile, acrylonitrile, neoprene, butyl rubber, etc. are examples of synthetic elastomers.

 

Polyvinyl alcohol, polyvinyl chloride, polyethylene, polypropylene, polyacrylate, polyamide, polyurea, polyvinylpyrrolidone, and polymethylmethacrylate are examples of synthetic polymers^13,14.

 

TOPICAL AND TRANSDERFMAL DRUG DELIVERY:

Due to various other benefits, transdermal route is believed to be the most common choice over the oral route²⁰. Also our skin, which forms about 16 percent of our body weight is believed to be the biggest organ in our human body. Although the list of the above mentioned benefits and the recent development exist, nowadays the on-the-market number of transdermal treatment applied commercially is approximately 40²¹. The stratum corneum, the outermost layer of the epidermis and a barrier, is the sole reason for why there are fewer products available. The stratum corneum, regarded as inert e-dermis, consists of keratin filaments which have built up and are covered by a cornified envelop, and are between a multilamellar lipid bi-layer²². The nature of the stratum corneum as a physical barrier and available structures in the skin provides both trans epidermal and trans appendageal routes through which drug molecules can be delivered into the skin²³. The latter is done through either an intercellular path, where the process occurs between the corneocytes, or a transcellular path, where the process occurs multiple times between the bilipid layers and the corneocytes. In the second case, the medication must pass via the eccrine, sebaceous, and hair glands. Topical or transdermal dose forms commonly include ointments, creams, gels, films and patches. Ointments and creams are not suitable to deliver drugs transdermally because they cannot offer the optimal contact times to improve drug absorption. Moreover, these dosage forms need to cover a large area of skin to achieve a higher medication release, advertising reduced patient acceptance and augmenting the risk of loss of drug²⁴.

 

 

Table 2. Transdermal medications supported by the United States drug food and drug administration^15,16,17,18

Drug	Therapeutic Use	Pharmacological Category	Key Advantage of Transdermal Delivery	Period of Introduction
Clonidine	Blood pressure control	Antihypertensive	Maintains steady plasma levels	1980s
Nitroglycerin	Angina prevention	Antianginal	Continuous vasodilatory effect	1980s
Scopolamine	Motion sickness	Anticholinergic	Long-duration action	1970s
Nicotine	Smoking cessation	CNS stimulant	Reduces withdrawal symptoms	1990s
Testosterone	Hormone deficiency	Androgen	Sustained hormone replacement	1990s
Estradiol	Menopausal symptoms	Estrogen	Improved bioavailability	1980s
Estradiol , Progestin	Hormone therapy	Combination hormone	Balanced hormonal regulation	1990s
Lidocaine	Neuropathic pain	Local anesthetic	Targeted pain relief	1990s
Fentanyl	Chronic pain	Opioid analgesic	High potency, sustained release	1990s
Oxybutynin	Overactive bladder	Antimuscarinic	Reduced systemic side effects	2000s
Methylphenidate	ADHD	CNS stimulant	Controlled daily dosing	2000s
Rivastigmine	Alzheimer’s disease	Cholinesterase inhibitor	Improved compliance	2000s
Selegiline	Depression	MAO inhibitor	Bypasses GI metabolism	2000s
Rotigotine	Parkinson’s disease	Dopamine agonist	Continuous dopaminergic delivery	2000s

 

 

Table 3. Devices for transdermal medication delivery systems on the market^28,29,30,31

Therapeutic Category	Drug	Clinical Application	Key Benefit of Transdermal Delivery
Cardiovascular Agents	Nitroglycerin	Management of ischemic heart conditions	Provides sustained vasodilation
Hormonal Therapy	Estradiol	Relief of menopausal symptoms	Maintains stable hormone levels
Androgen Replacement	Testosterone	Treatment of male hormone deficiency	Avoids hepatic metabolism
CNS Stimulant Therapy	Nicotine	Aid in smoking cessation	Reduces withdrawal symptoms
Estrogen Therapy	Estradiol	Hormone replacement therapy	Improved patient compliance

 

Aceclofenac nanogels were created utilizing chitosan, egg albumin, and nanoparticles as a transdermal medication delivery mechanism, and they were distributed in carbopol 940 gel²⁵. The best nanogel demonstrated prolonged aceclofenac penetration more than 8 hours. Optimized gel was observed to be more permeative by flux and anti-inflammatory in vivo in comparison to the commercial His 5-fluorouracil-loaded chitin spherical particle nanogel²⁶. It demonstrated pH- dispersed drug delivery and toxicity in melanoma cells (A375) nonetheless it was not demonstrated to be better. Zidovudine, an anti-HIV drug, is toxic to human dermal fibroblast cell lines with a short half-life of one hour giving them a high dosage, which needs to be ingested frequently. Due to this the toxicity and non-compliance of the patient were frequent. To overcome the problems mentioned above a transdermal cross-linked chitosan zidovudine film was developed. Other permeation enhancers that are present in the 5% oleic acid content of the film include menthol, cineol and Tween 80^26,27.

 

CONCLUSION:

Over the past 15 years, the development and optimization of novel transdermal systems have drawn significant research interest. This is primarily driven by ongoing efforts to achieve efficacious transdermal delivery of larger, complex molecules, including peptides, proteins, and vaccines, alongside conventional drugs. As the global market eagerly awaits the commercialization of several advanced transdermal therapeutics, percutaneous absorption is poised to make substantial contributions to clinical medicine in the coming years.

 

REFERENCES:

1.      Rai VK, Mishra N, Agrawal AK, Jain S, Yadav NP. Novel drug delivery system: an immense hope for diabetics. Drug Deliv. 2016; 23(7): 2371–90.

2.      Larraneta E, Lutton REM, Woolfson AD, Donnelly RF. Microneedle arrays as transdermal and intradermal drug delivery systems: materials science, manufacture and commercial develop- ment. Mater Sci Eng R Rep. 2016; 104: 1–32.

3.      Sivamani RK, Liepmann D, Maibach HI. Microneedles and trans- dermal applications. Expert Opin Drug Deliv. 2007; 4(1): 19–25.

4.      Daddona PE, Matriano JA, Mandema J, Maa YF. Parathyroid hor- mone (1-34)-coated microneedle patch system: clinical pharmaco- kinetics and pharmacodynamics for treatment of osteoporosis. Pharm Res. 2011; 28(1): 159–65.

5.      Arnou R, Icardi G, De Decker M, Ambrozaitis A, Kazek M-P, Weber F, et al. Intradermal influenza vaccine for older adults: a randomized controlled multicenter phase III study. Vaccine. 2009; 27(52): 7304–12

6.      Rai VK, Mishra N, Yadav KS, Yadav NP. Nanoemulsion as phar- maceutical carrier for dermal and transdermal drug delivery: formu- lation development, stability issues, basic considerations and appli- cations. J Control Release. 2018; 270: 203–25.

7.      Sahoo SK, Parameshwar K, Rasheed SH, Kumar CA, Brahma DK, Pavani CH, Reddy KM. A comprehensive update on nanoparticle in targeting of skin cancer therapy: recent updates, challenges, and future perspectives. Research Journal of Pharmacy and Technology. 2024; 17(6): 2985-9.

8.      Rasheed SH, Tirumoorthy N, Kundlik G. Enhanced transdermal delivery of ketoconazole via ethosomes formulation and evaluation. World J Pharm Pharm Sci. 2007; 1(1): 238-49.

9.      Aruna M, Rasheed SH. Formulation and in-vitro evaluation of niosomal drug delivery system for aceclofenac. International Journal of Research in Pharmaceutical Sciences and Technology. 2020; 3(1): 84-8.

10.   Kim Y-C, Park J-H, Prausnitz MR. Microneedles for drug and vaccine delivery. Adv Drug Deliv Rev. 2012; 64(14): 1547–68.

11.   Bora P, Kumar L, Bansal A. Microneedle technology for advanced drug delivery: evolving vistas. Curr Res Inf Pharm Sci. 2008; 9.

12.   Gupta Durgesh Kumari, Goswami Raksha, Kumawat Deepak, Gupta Anjana, Chandy Steffy Mary. A Review on Chitosan Nanoparticle as a Drug delivery system. Asian J. Pharm. Res. 2020; 10(4): 299-306.

13.   S. More, T. Ghadge, S. Dhole. Microneedle: an Advanced Technique in Transdermal Drug Delivery System. Asian J. Res. Pharm. Sci. 2013; 3(3): 141-148.

14.   Tuan-Mahmood TM, McCrudden MT, Torrisi BM, McAlister E, Garland MJ, Singh TR, et al. Microneedles for intradermal and transdermal drug delivery. Eur J Pharm Sci. 2013; 50(5): 623–37.

15.   Ita K. Transdermal delivery of drugs with microneedles—potential and challenges. Pharmaceutics. 2015; 7(3): 90–105.

16.   Rasheed SH, Parameshwar K, Reddy KM, Sushmitha G, Madhavi MS. Nanotechnology-Driven Innovations in Malaria Treatment and Control: Current Challenges and Pharmaceutical Strategies. Asian Journal of Pharmaceutical Research. 2024; 14(3): 235-41.

17.   Rasheed SH, Parameshwar K, Reddy KM, Sushmitha G, Madhavi MS. Nanotechnology-Driven Innovations in Malaria Treatment and Control: Current Challenges and Pharmaceutical Strategies. Asian Journal of Pharmaceutical Research. 2024; 14(3): 235-41.

18.   Tabassum N, Sofi A, Khuroo T. Microneedle technology: a new drug delivery system. Int J Res Pharmaceut Biomed Sci. 2011; 2: 59–62.

19.   Bariya SH, Gohel MC, Mehta TA, Sharma OP. Microneedles: an emerging transdermal drug delivery system. J Pharm Pharmacol. 2012; 64(1): 11–29.

20.   Subrahmanyam P, Srinivas B, Rasheed SH, Parameshwar K. Graphene-based nanomaterials in precision medicine for next-generation therapeutics: merging advances, therapeutic potentials, and translational challenges E. Asian Journal of Pharmacy and Pharmacology. 2025; 11(3): 35-44.

21.   Rasheed SH, Tirumoorthy N, Kundlik G. Enhanced transdermal delivery of ketoconazole via ethosomes formulation and evaluation. World J Pharm Pharm Sci. 2007; 1(1): 238-49.

22.   Waghule T, Singhvi G, Dubey SK, Pandey MM, Gupta G, Singh  M, et al. Microneedles: a smart approach and increasing potential for transdermal drug delivery system. Biomed Pharmacother. 2019; 109: 1249 - 58.

23.   Anitha T, Sathish Kumar K.. Comparative Study of Adsorption for Chitosan, Sand and Chitosan Coated Sand. Asian J. Pharm. Tech. 2013; 3 (4): 185-188.

24.   R.B. Saudagar, S. Samuel. Ethosomes: Novel noninvasive carrier for Transdermal Drug Delivery. Asian J. Pharm. Tech. 2016; 6(2): 135-138.

25.   AVS Madhu Latha, T Naga Ravi Kiran, J N Suresh Kumar. Formulation, Optimization and Evaluation of Glibenclamide Transdermal Patches by using chitosan Polymer. Asian J. Pharm. Tech. 2019; 9(1): 01-07.

26.   A. Lakshmi Usha, M. Kusuma Kumari, E. Radha Rani, A.V.S. Ksheera Bhavani. A Novel Technique for Intra Transdermal Delivery of Drugs – Coated Polymeric Needles. Asian J. Pharm. Tech. 2020; 10(4): 289-295.

27.   Kiran Patil, Vasant Helavi. Synthesis of Pyranopyrazoles by using Chitosan Hydrogel as a green and recyclable catalyst. Asian J. Research Chem. 2018; 11(2): 477-484.

28.   Nikhil Patel, Chetan Patel, Savan Vachhani, ST Prajapati, CN Patel. Recent Advances in Transdermal Drug Delivery System. Research J. Pharma. Dosage Forms and Tech. 2010; 2(2): 113-119.

29.   Vivek Jain, Gopal Garg, U.K. Patil, Shailesh Jain. Recent Perspectives of Chitosan: A Review. Research J. Pharma. Dosage Forms and Tech. 2010; 2(3): 220-224 .

30.   Punasiya R, Joshi A, Gupta S, Punasiya J. Transfersomes- A Novel Carrier for Transdermal Drug Delivery. Research J. Pharma. Dosage Forms and Tech. 2010; 2(2): 133-138

31.   Megha B. Hiroji, Nagesh C., Devdatt Jani, Chandrashekhar S.. Development and Evaluation of Transdermal Drug Delivery System using Natural Polysaccharides. Research J. Pharma. Dosage Forms and Tech. 2012; 4(5): 278-284.

 

 

 

 

Received on 24.08.2022      Revised on 12.04.2025 Accepted on 27.05.2026      Published on 01.07.2026 Available online from July 04, 2026 Research J. Pharmacy and Technology. 2026;19(7):3388-3392. DOI: 10.52711/0974-360X.2026.00481 © RJPT All right reserved
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